{"paper_id":"4b6d81e1-d0bb-43a5-a9d0-9d5f8aefca6c","body_text":"Jaripur et al. \nReproductive Biology and Endocrinology          (2022) 20:110  \nhttps://doi.org/10.1186/s12958-022-00982-7\nRESEARCH\nThe effects of magnesium supplementation \non abnormal uterine bleeding, alopecia, quality \nof life, and acne in women with polycystic ovary \nsyndrome: a randomized clinical trial\nMahsima Jaripur1, Hatav Ghasemi‑Tehrani2, Gholamreza Askari1, Mahsa Gholizadeh‑Moghaddam1, \nCain C. T. Clark3 and Mohammad Hossein Rouhani1* \nAbstract \nBackground: Abnormal uterine bleeding (AUB), alopecia, low quality of life, and acne are considered as complica‑\ntions of polycystic ovary syndrome (PCOS). We hypothesized that magnesium supplementation would yield beneficial \neffects on PCOS related complications.\nObjective: To examine the effects of magnesium supplementation on AUB, alopecia, quality of life, and acne.\nMethods: In this parallel randomized clinical trial, we randomly assigned 64 women with PCOS to the magnesium \ngroup (n = 32) or placebo group (n = 32) for 10 weeks. AUB, alopecia, quality of life, and acne were assessed by the \nInternational Federation of Gynecology and Obstetrics criterion, the Sinclair Scale, the Health Survey Quality of Life \nQuestionnaire, and the Global Acne Grading System, respectively. This randomized clinical trial was registered at IRCT.\nir (IRCT20130903014551N9).\nResults: Magnesium supplementation significantly improved the components of quality of life including physical \nfunctioning (p = 0.011), role limitations due to physical health (p = 0.012), role limitations due to emotional problems \n(p < 0.001), energy/fatigue (p = 0.005), emotional wellbeing (p < 0.001), social functioning (p = 0.002), general health \n(p = 0.013), and total quality of life (p < 0.001), compared with placebo. No significant effect was observed on acne, \nalopecia, and AUB.\nConclusion: Magnesium supplementation in women with PCOS had a significant positive effect on improving total \nquality of life.\nTrial registration: This randomized clinical trial was registered at IRCT.ir on 2020–10‑18 (Registration Code: \nIRCT2 01309 03014 551N9).\nKeywords: Polycystic ovary syndrome, Magnesium, Acne, Quality of life, Alopecia, Abnormal uterine bleeding\n© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which \npermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the \noriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or \nother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line \nto the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory \nregulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this \nlicence, visit http:// creat iveco mmons. org/ licen ses/ by/4. 0/. The Creative Commons Public Domain Dedication waiver (http:// creat iveco \nmmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nIntroduction\nPolycystic ovary syndrome (PCOS) is characterized by \nseveral cysts and follicles in enlarged ovaries, and pro -\nduction of infertile eggs [1]. Genetic and environmental \nfactors, including dietary intakes, are contributing factors \nof PCOS [2]. The World Health Organization estimates \nthat 116 million women worldwide have PCOS; and its \nOpen Access\n*Correspondence:  sm_rouhani@nutr.mui.ac.ir\n1 Food Security Research Center and Department of Community Nutrition, \nSchool of Nutrition and Food Science, Isfahan University of Medical Sciences, \nIsfahan, Iran\nFull list of author information is available at the end of the article\n\nPage 2 of 11Jaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \nprevalence varies from 2 to 26%, globally [3]. Symptoms \nof PCOS include abnormal uterine bleeding (AUB) and \nsigns of excess androgens secretion, such as acne, male \npattern alopecia, and low quality of life [1].\nAUB is prevalent among women with PCOS; indeed, \nevidence suggests that 50% of patients had oligomenor -\nrhea and 20% had amenorrhea [4]. Androgenic alope -\ncia is another complication of PCOS and it is a leading \ncauses of hair loss in women [5], where, up to, 67% of \nwomen with PCOS suffer from androgenic alopecia [5]. \nOne of the most common signs of androgen overload in \nPCOS is acne [6], which is an inflammatory disease of \nthe hair follicles and apocrine glands that occurs in more \nthan one-third of women with PCOS [7]. Researchers \nhave shown that the quality of life in women with PCOS \nis lower than healthy subjects and even compared to \nthose women with other gynecological diseases [8]. Infer-\ntility, menstrual irregularities, hirsutism, acne, hair loss, \nanxiety and depression are possible causes of low quality \nof life in PCOS [9].\nEvidence suggests that magnesium deficiency may play \nan important role in women’s health in several clinical \nconditions, including premenstrual syndrome, dysmen -\norrhea, and PCOS [10]. Women with PCOS have lower \nserum magnesium levels than healthy people [11]. Mag -\nnesium can help reduce menstrual pain and cramps \n[12], and is involved in the formation of proteins, cell \ngrowth, and division cell involved in hair. Therefore, it is \nposited that magnesium intake can improve hair loss in \nwomen [13]. Magnesium may also have beneficial effect \non skin lesions and acne; for instance, previous stud -\nies have shown that magnesium improves collagen pro -\nduction in the skin, whilst low magnesium intake may \ncause inflammation [14]. Also, serum magnesium levels \nhave been shown to be low in patients with acne [15], \nand co-supplementation of magnesium and myoinositol \nwas reported to improve acne [16] Magnesium may have \nfavorable effect on components of quality of life includ -\ning depression [17, 18], where previous studies showed \nthat magnesium supplementation improved depression \nin diabetic and non-diabetic patients [19, 20].\nAccording to previous studies, we hypothesized that \nmagnesium supplementation might elicit beneficial \neffects on complications of PCOS. Therefore, this study \nsought to evaluate the effect of magnesium supplementa-\ntion on AUB, alopecia, quality of life, and acne in women \nwith PCOS.\nMethod\nThis study was carried out in the period of Novem -\nber 2020 to November 2021 in Isfahan, Iran. Subjects \nwere included if they: 1) were aged 18 to 45 years old; 2) \nwere diagnosed with PCOS according to the Rotterdam \ncriteria [21]; 3) had no change in the dose of the medica -\ntions or did not start taking a new medication during the \nprevious 14 days; 4) were not in menopause; and 5) did \nnot take vitamin and mineral supplements. Subjects who \nchanged dose of medications or started taking new drugs \nwere excluded. Also, we excluded patients who were \npregnant or menopausal during the study.\nTo find the eligible participants, we screened the \nrecords of subjects who registered as PCOS patients in \nShahid Beheshti Obstetrics and Gynecology Hospital, \nIsfahan, Iran. We called them to evaluate whether they \nhad signs and symptoms of PCOS. Then women who \nreported signs and symptoms of PCOS were invited to \nrun an assessment based on the Rotterdam criteria to \nensure that they had PCOS. According to the Rotter -\ndam criteria, subjects who had two of the following three \nsymptoms were diagnosed as having PCOS: 1) anovula -\ntion or ovulatory dysfunction; 2) increased serum con -\ncentration of androgens; and 3) at least 12 follicles in each \novary known as polycystic ovaries on ultrasound [21]. \nBefore including in the study, women were assessed for \nthese criteria and then subjects who had two of the three \nsymptoms were selected for the study. The International \nevidence-based guideline for the assessment and man -\nagement of PCOS emphasizes where irregular menstrual \ncycles and hyperandrogenism are present, ultrasound is \nnot necessary. Therefore, ultrasound was not performed \nfor women with irregular menstrual cycles and hyper -\nandrogenism[22] All subjects were outpatients referred \nto clinic of Shahid Beheshti Obstetrics and Gynecology \nHospital, Isfahan, Iran. All patients enrolled in this study \nwanted to be pregnant. Shahid Beheshti Obstetrics and \nGynecology Hospital focuses on infertility and women \nwho want to be pregnant are referred to this center. Sub -\njects referred to this center are categorized based on the \nmain cause of infertility. We used records of subjects \nwho could not be pregnant because of PCOS. We did not \ninclude admitted women.\nTo calculate required sample size, score of quality of \nlife was considered as the main outcome variable. Based \non the previous studies, we considered ∆ = 0.47 and \n S2 = 0.66 [23]. According to the following equation, in \nwhich α = 0.05 and β = 0.20 (the power of the study was \n80%), the estimated minimum sample size in each group \nwas 30:\nn = 2 [(Z1-α / 2 + Z1-β) 2 ×  S2] / Δ 2 = 2 [(1.96 + 0.85) \n2 × (0.66) 2] / (0.47) 2 = 30.\nFinally, 64 subjects (n = 32 in each group) were included \nin the study because of possible withdrawal. Participants \nwere randomly allocated in a ratio of 1:1 to either mag -\nnesium supplement or placebo using a computer-gener -\nated randomization sequence. We did not use blocks in \nrandomization. We assigned a code to each subject and \n\nPage 3 of 11\nJaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n \nentered the codes into SPSS. Then participants were ran -\ndomly divided in to 2 groups by SPSS.\nRandomization list and numbering of supplements \ncontainers were performed by staff who had no contri -\nbution in the intervention and assessment of the out -\ncomes. Therefore, investigators who evaluated outcomes \nwere blinded. All participants signed a written consent \nform prior to participation. This study was ethically \napproved by The Research Council and Ethical Com -\nmittee of Isfahan University of Medical Sciences, Isfa -\nhan, Iran, (Code: IR.MUI.RESEARCH.REC.1399.406). \nThis randomized clinical trial was registered at IRCT.ir \n(IRCT20130903014551N9).\nIntervention\nComprehensive information regarding the study were \nexplained to participants. In the magnesium group, a \n250 mg magnesium oxide tablet (Magni One ® produced \nby DonyaDarou, Tehran, Iran) per day was administered \nfor 10 weeks. In placebo group, we used a tablet that con-\ntained 5 mg starch and its color, appearance, smell, and \ntaste were similar to the 250 mg magnesium oxide tablet. \nParticipants were asked to consume tablets after break -\nfast. We used telephone calls and virtual networks to \nmonitor use of supplements.\nWomen in both groups received a list of dietary recom-\nmendations, including: 1) limit consumption of refined \nor simple carbohydrates, such as white bread, white rice, \nsugar and sweets; 2) increase consumption of fresh veg -\netables; 3) use more mini-meals instead of big meals; 4) \ndrink at least 8 glasses of fluid, especially water; 5) be \ncautious about your weight and avoid overeating; 6) con -\nsume leafy vegetables such as lettuce and cabbage instead \nof starchy vegetables such as potatoes; 7) increase con -\nsumption of fresh fruits and avoid using industrial and \nsugar sweetened fruit juices; 8) limit consuming salty \nfoods, fast foods and high-fat dairy products; and 9) use \nhealthy oils such as olive oil and canola oil and limit con -\nsuming saturated, partially saturated vegetable oil or ani -\nmal fat.\nEvaluation of AUB\nBased on the definitions provided by the International \nFederation of Gynecology and Obstetrics (FIGO), fol -\nlowing criteria were considered as components of AUB \n[24, 25]:\n1) Frequency of menses: The duration of the men -\nstrual cycle is normally 24 to 38  days. Therefore, \nregular episodes of bleeding at intervals of ≤ 24 days \nor > 38 days were considered as abnormal.\n2) Regularity of menses: Irregular menses was defined \nas shortest to longer cycle variation was ≥ 10 days.\n3) Duration of menses: If the duration of menstrual \nbleeding was more than 8 days or less than 3 days in \neach period, it was considered as abnormal\n4) Volume of monthly blood loss: If a woman’s bleeding \nvolume was between 5 to 80  ml in a period, it was \nconsidered normal and less than 5 ml or more than \n80 ml was abnormal.\nThe number of AUB criteria in each subject was \nassessed at baseline and after 10 weeks of intervention.\nEvaluation of male pattern hair loss\nClinical manifestations of alopecia was assessed at the \nbeginning and end of the study using the Sinclair Scale \n[26]. The validity and reliability of this method have \nbeen accepted in previous studies [27]. No manifesta -\ntion of alopecia was defined as the first stage, alopecia in \nthe center of the scalp was categorized as second stage, \nexpanded alopecia in the center of scalp and hair loss \nin lateral area was considered as the third stage, in the \nfourth stage, a bald spot could be detectable on the ante -\nrior portion of the scalp, and finally, advanced alopecia \nwas categorized as the fifth stage [28].\nAssessment of acne\nTo evaluate the severity of acne, we examined existence \nof acne according to Global Acne Grading System [29]. \nValidity and reliability of this method was acceptable in \nprevious studies [30, 31]. In this scoring system, fore -\nhead, right cheek, left cheek, nose, chin, upper back, and \nchest were assessed. A factor was defined for each are: \nforehead = 2, right cheek = 2, left cheek = 2, nose = 1, \nchin = 1, chest and upper back = 3. We scored each type \nof lesion based on the severity: no lesions = 0, come -\ndones = 1, papules = 2, pustules = 3 and nodules = 4. \nLocal score for each area was calculated according to \nthe following formula: Local score = Factor × Lesion \nscore (0–4). The total score was calculated by summing \nlocal scores, and acne severity was defined as mild (score \nof 1–18), moderate (score of 19–30), severe (score of \n31–38), and very severe (score of > 39) [29]. Clinical man-\nifestations of acne was assessed at the beginning and end \nof the study.\nAssessment of Quality of Life\nTo assess the effect of magnesium on quality of life, we \nasked patients to complete the Health Survey Quality of \nLife Questionnaire (SF-36) before and after the interven -\ntion [32, 33]. The validity and reliability of this question -\nnaire was evaluated and the results were accepted [34, \n35]. The SF-36 could assess eight scales: physical func -\ntioning (PF), role physical (RP), bodily pain (BP), gen -\neral health (GH), vitality (VT), social functioning (SF), \n\nPage 4 of 11Jaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \nemotional role (ER), and mental health (MH) [36]. The \ntotal score was equal to the average of scores in each \neight subscales. Higher scores were interpreted as higher \nquality of life [37].\nAssessment of physical activity\nPhysical activity of the participants was presented as \nmetabolic equivalent per hour per day (MET.h.d). Each \nparticipant completed 5 one-day physical activity diaries \nduring the study. Individuals were asked to report their \nactivities such as walking, exercise, sleep, watching TV, \nhousework, studying, bathing, and so on. The total met -\nabolic equivalent was calculated by multiplying the fre -\nquency, duration, and intensity of each physical activity \nin 24 h.\nDietary intake\nTo assess dietary intakes during the study, each par -\nticipant was asked to complete 5 one-day food records, \nincluding 3 weekdays and 2 weekends. Nutrient content \nof the foods was calculated by Nutritionist IV based on \nthe United States Department of Agriculture food com -\nposition database.\nBiochemical assessment\nThe serum level of magnesium was measured at baseline. \nA 5  ml blood sample was collected and serum was iso -\nlated. We measured magnesium by Atomic Absorption \nSpectrophotometry method.\nSocioeconomic status\nTo classify patients in terms of economic status, they \nwere asked about the amount of family income and based \non the amount of income, they were classified into three \ngroups: 1) Poor economic status (for incomes less than \nthree million ،Tomans per month), 2) Medium economic \nstatus (monthly income Between four to ten million \nTomans) and 3) Good economic situation (for people \nwhose average family income was above ten million \nTomans per month). This division was based on living \nconditions in Iran and the income range of clients. The \nlevel of education of each person was asked, and they \nwere divided into three groups: 1) under diploma, 2) \nDiploma, and 3) University education.\nStatistical Analysis\nWe ran an intention to treat (ITT) analysis by using the \nlinear regression method in the current study [38]. The \nKolmogorov–Smirnov test and visual inspection of Q-Q \nplots were applied to evaluate normal distribution, and \nno variables had a large deviation from normal distribu -\ntion. The comparison of qualitative variables between \nthe magnesium and placebo groups was conducted using \nthe Chi-square test, whilst nominal and ordinal variables \nwere reported as percentage. Within group comparison \n(baseline vs. endpoint) was performed using Paired T \ntest analysis. Inter-groups comparisons were performed \nusing Independent Student t-test for numerical vari -\nables. We adjusted the effect of the confounding variables \n(baseline serum magnesium, energy intake and baseline \nvalues) using analysis of covariance (ANCOVA). Scale \nvariables were reported as mean ± standard deviation. All \ndata analyses were conducted using SPSS version 21 sta -\ntistical software, with an a priori alpha level of 0.05.\nResult\nThe process of patient recruitment is shown in Fig.  1. To \nfind the eligible participants, we screened the records of \noutpatients referred to clinic of Shahid Beheshti Obstet -\nrics and Gynecology Hospital, Isfahan, Iran. Initially, the \nrecords of subjects registered as PCOS patients were \nscreened (n = 844). Then we called them and 780 patients \nwere excluded because: 1) they did not meet the inclu -\nsion criteria (n = 376); 2) PCOS was treated (n = 24); 3) \npatients were on insemination in vitro fertilization treat -\nments (n = 50); 4) they refused to participate in the study \n(n = 248); 5) they were pregnant (n = 20); or 6) other \nreasons (n = 52). Then women who reported signs and \nsymptoms of PCOS were invited to run an assessment \nbased on the Rotterdam criteria to ensure that they had \nPCOS [21]. Therefore, 64 patients were included in the \nstudy and they were randomly assigned into magnesium \n(n = 32) or placebo (n = 32). During the follow-up pro -\ncess, five patients in the magnesium group were lost to \nfollow-up because they: 1) refused to continue the study \n(n = 2); 2) were pregnant (n = 1); or 3) did not want to \nparticipate in blood sampling (n = 2). Similarly, five sub -\njects were lost to follow-up in the placebo group because \nthey: 1) refused to continue the study (n = 2); 2) did not \nwant to participate in blood sampling (n = 2); or 3) per -\nsonal reasons (n = 1). Therefore, 54 patients completed \nthe study. Nevertheless, data of 64 people (32 subjects in \neach group) were analyzed based on the ITT method.\nTable  1 shows general characteristics of the partici -\npants. Results demonstrated that age (p = 0.615), height \n(p = 0.439), weight (p = 0.918), weight status (p = 0.987), \nBMI (p = 0.808), educational status (p = 0.382), economic \nstatus (p = 0.186), marital status (p = 0.306), and the level \nof physical activity (p = 0.733) were not different between \ntwo groups. Baseline serum magnesium was higher in the \nintervention group compared with placebo (p = 0.047). \nMore data regarding physical activity are presented in the \nSupplementary File 1.\nTable  2 shows intake of nutrients (per 1000  kcal) \nof subjects during the study. The intake of carbohy -\ndrate (p = 0.325), protein (p = 0.583), fat (p = 0.760), \n\nPage 5 of 11\nJaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n \nFig. 1 CONSORT study flow diagram\nTable 1 General Characteristics of the participants\nBMI Body mass index\n1 Mean ± SD\nVariable Magnesium (n = 32) Placebo (n = 32) P\nAge (y) 31.69 ± 5.411 32.44 ± 6.42 0.615\nWeight (kg) 69.88 ± 14.36 70.22 ± 12.22 0.918\nHeight (m) 1.6 ± 0.07 1.62 ± 0.05 0.439\nBMI (kg/m2) 26.89 ± 4.68 26.63 ± 4.06 0.808\nOverweight/Obese (%) 68.5 68.7 0.987\nEducation (%)\n  Did not complete high school 25 15.6 0.382\n  High school 46.9 40.6\n  University degree 28.1 43.8\nEconomic Status (%)\n  Low 18.8 9.4 0.186\n  Medium 71.9 65.6\n  High 9.4 25\n  Married (%) 90.6 96.9\n  Physical Activity (Met/h) 1.1 ± 0.13 1.11 ± 0.17 0.733\n  Serum magnesium (mg/dl) 2.35 ± 0.21 2.25 ± 0.17 0.047\n\nPage 6 of 11Jaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \ncholesterol (p = 0.102), linoleic acid (p = 0.480), satu -\nrated fatty acids (p = 0.591), monounsaturated fatty \nacids (p = 0.332), polyunsaturated fatty acids (p = 0.959), \nvitamin A (p = 0.434), vitamin E (p = 0.704), vitamin K \n(p = 0.403), vitamin C (p = 0.086), vitamin B1 (p = 0.250), \nvitamin B2 (p = 0.386), vitamin B3 (p = 0.532), vitamin \nB5 (p = 0.312), vitamin B6 (p = 0.179), folate (p = 0.859), \nmagnesium (p = 0.481), potassium (p = 0.341), calcium \n(p = 0.606), zinc (p = 0.560), iron (p = 0.609), sodium \n(p = 0.561), and dietary fiber (p = 0.412) had no signifi -\ncant differences between the two groups.\nTable 3 shows the effects of magnesium supplementa -\ntion on components of quality of life, AUB, alopecia, and \nacne. In the magnesium group, scores of physical func -\ntioning (p = 0.011), role limitations due to physical health \n(p = 0.012), role limitations due to emotional problems \n(p < 0.001), energy/fatigue (p = 0.005), emotional well -\nbeing (p < 0.001), social functioning (p = 0.002), general \nhealth (p = 0.013), and total quality of life (p < 0.001) were \nsignificantly improved after intervention compared with \nbaseline. In contrast, number of AUB items (p < 0.001) \nand score of alopecia (p = 0.009) decreased after the trial \nin magnesium group. In placebo group, scores of physi -\ncal functioning (p = 0.028), number of items of AUB \n(p = 0.001) and score of alopecia (p = 0.009) were signif -\nicantly decreased at the end of the trial compared with \nbaseline. More data regarding alopecia, acne, physical \nactivity, AUB scores are presented in the Supplementary \nFile 1.\nAfter adjusting for baseline serum magnesium and \ninitial measurements, magnesium supplementation \nimproved scores of role limitations due to emotional \nproblems (p = 0.001),  energy/fatigue (p = 0.010), emo -\ntional wellbeing (p < 0.001), general health (p = 0.042), \nand total quality of life (p < 0.001) compared with placebo.\nDiscussion\nThe results of this study showed that supplementation \nwith 250  mg of magnesium for 10  weeks improved the \nquality of life components in women with PCOS. Quality \nof life in PCOS is lower than healthy subjects and those \nwith other gynecological diseases, which can lead to \nTable 2 Nutrient intake (per 1000 kcal) of subjects during the study\na  Variables are expressed as mean ± SD\nb  All variables were adjusted for total energy intake\nNutrients Magnesium (n = 32) Placebo (n = 32) P\nCarbohydrate (g/day) 133.24 ± 102.81 113.11 ± 21.94 0.325\nProtein (g/day) 34.04 ± 9.65 32.61 ± 9.16 0.583\nFat (g/day) 48.69 ± 10.85 47.77 ± 11.036 0.760\nCholesterol (mg/day) 111.90 ± 60.55 144.88 ± 81.53 0.102\nLinoleic acid (gr/day) 0.32 ± 1.03 0.09 ± 0.14 0.664\nSaturated fatty acids (g/day) 10.40 ± 2.56 9.88 ± 4.20 0.591\nMonounsaturated fatty acids (g/day) 14.72 ± 11.84 12.35 ± 4.13 0.332\npolyunsaturated fatty acids (g/day) 20.45 ± 7.48 20.56 ± 8.33 0.959\nVitamin A (re/day) 287.06 ± 251.52 368.65 ± 466.13 0.434\nVitamin E (mg/day) 1.96 ± 2.041 1.74 ± 2.07 0.704\nVitamin K (ug/day) 36.86 ± 26.47 43.95 ± 34.07 0.403\nVitamin C (mg/day) 68.77 ± 42.92 50.58 ± 32.13 0.086\nVitamin B1 (mg/day) 0.81 ± 0.16 0.75 ± 0.18 0.250\nVitamin B2 (mg/day) 0.84 ± 1.38 0.61 ± 0.12 0.386\nVitamin B3 (mg/day) 11.22 ± 4.03 10.49 ± 4.39 0.532\nVitamin B5 (mg/day) 2.29 ± 0.80 1.98 ± 0.71 0. 312\nVitamin B6 (mg/day) 0.67 ± 0.21 0.74 ± 0.32 0. 179\nVitamin B9 (µg/day) 118.14 ± 48.55 112.70 ± 41.92 0. 859\nmagnesium (mg/day) 96.79 ± 24.49 91.20 ± 32.12 0.481\nPotassium (mg/day) 1035.03 ± 187.17 973.87 ± 267.42 0.341\nCalcium (mg/day) 278.53 ± 115.69 265.01 ± 69.31 0.606\nZinc (mg/day) 3.68 ± 1.26 3.38 ± 1.06 0.531\nIron (mg/day) 8.43 ± 2.41 8.80 ± 2.75 0.609\nSodium (mg/day) 517.80 ± 213.30 555.11 ± 248.57 0.561\nDietary Fiber (g/day) 7.12 ± 2.60 6.54 ± 2.52 0.412\n\nPage 7 of 11\nJaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n \nTable 3 The effects of magnesium supplementation on components of quality of life, abnormal uterine bleeding, alopecia and acne a\na  Variables are expressed as mean ± SD\nb  Obtained from Paired T test comparing baseline and endpoint values within each group\nc  Obtained from Independent t-test comparing endpoint measurements between two groups\nd  Obtained from ANCOVA, adjusted for baseline value of each factor and baseline serum magnesium comparing endpoint values between two groups\n* P < 0.05\nVariables Magnesium (n = 32) Placebo (n = 32) Pc Pd\nBaseline End of trial Change Pb Baseline End of trial Change Pb\nComponents of quality of life\n  Score of Physical functioning 60.00 ± 18.66 67.53 ± 18.64 7.53 ± 15.66 0.011* 65.78 ± 26.79 60.31 ± 25.99 ‑5.46 ± 13.46 0.028* 0.207 0.053\n  Score of Role limitations due to physical health 38.12 ± 45.66 54.21 ± 46.45 16.09 ± 34.00 0.012* 41.40 ± 48.61 45.46 ± 47.42 4.06 ± 31.09 0.465 0.459 0.093\n  Score of Role limitations due to emotional problems 9.89 ± 25.34 62.60 ± 42.37 52.70 ± 43.88  < 0.001* 22.92 ± 41.21 29.63 ± 43.09 6.71 ± 29.39 0.206 0.003 0.001*\n  Score of Energy/ fatigue 30.31 ± 26.42 40.37 ± 24.89 10.06 ± 18.83 0.005* 38.90 ± 28.70 37.18 ± 29.72 ‑1.71 ± 5.90 0.110 0.644 0.010*\n  Score of Emotional well being 31.43 ± 25.51 39.84 ± 30.12 14.90 ± 18.26  < 0.001* 42.65 ± 28.05 39.84 ± 30.12 ‑2.81 ± 14.19 0.271 0.345  < 0.001*\n  Score of Social functioning 40.00 ± 33.09 54.84 ± 32.04 14.84 ± 25.47 0.002* 49.60 ± 42.65 57.73 ± 53.90 8.12 ± 44.89 0.314 0.795 0.428\n  Score of Pain 54.29 ± 36.28 60.70 ± 33.40 6.40 ± 19.24 0.069 66.01 ± 32.98 63.59 ± 33.21 ‑2.42 ± 13.80 0.329 0.730 0.270\n  Score of General health 43.43 ± 30.25 43.51 ± 30.29 5.20 ± 10.96 0.013* 43.43 ± 30.25 43.51 ± 30.29 0.07 ± 5.33 0.934 0.643 0.042*\n  Total Score of Quality of life 37.90 ± 15.60 47.26 ± 17.65 9.35 ± 8.67  < 0.001* 47.05 ± 22.26 44.85 ± 21.40 ‑2.20 ± 7.91 0.126 0.624  < 0.001*\n  Number of items of AUB 2.13 ± 1.07 1.19 ± 1.03 ‑0.93 ± 0.94  < 0.001* 1.91 ± 1.32 1.19 ± 1.06 ‑0.71 ± 1.14 0.001* 0.999 0.651\n  Score of alopecia 1.94 ± 1.07 1.31 ± 0.93 ‑0.62 ± 1.26 0.009* 1.94 ± 0.98 1.31 ± 0.93 ‑0.62 ± 1.26 0.009* 0.999 0.958\n  Score of acne 1.48 ± 2.791 1.00 ± 2.191 ‑0.48 ± 1.54 0.092 0.94 ± 2.735 0.13 ± 0.707 ‑0.81 ± 2.86 0.119 0.041* 0.051\n\nPage 8 of 11Jaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \nseveral negative consequences [39, 40, 39]. Therefore, the \nquality of life in these patients is clinically important [41]. \nAccordingly, the results of this study suggest that mag -\nnesium supplementation might be effective in improving \nquality of life in PCOS.\nPrevious studies confirmed that magnesium supple -\nmentation had a favorable effect on quality of life. Indeed, \na clinical trial showed that oral magnesium sulfate signif -\nicantly improved the quality of life in women with dys -\nmenorrhea [42], whilst according to another study, it was \nobserved that patients with fibromyalgia had a significant \nimprovement in quality of life by using magnesium sup -\nplements [43]. Also, adjuvant therapy with magnesium \nsulfate reportedly resulted in a significant improvement \nin quality of life components and beneficial changes in \nthe psycho-emotional state of patients with the chronic \ncoronary syndrome [44]. Moreover, magnesium sup -\nplementation improved the quality of life in patients \nwith asthma [45]. Therefore, findings of previous studies \nregarding improvement of quality of life are concordant \nwith the results of the present study.\nWe found that magnesium supplementation had no \nsignificant effect on acne in patients with PCOS. Acne \nvulgaris is a cosmetic problem that affects 80% of the \npopulation, especially women with PCOS [46]. It is a \nchronic inflammatory disease with multifactorial causes \nand clinical manifestations of blackheads, papules, pus -\ntules, nodules, and cysts [47]. Using topical magnesium \nhas been reported to result in increased skin hydration \nand skin permeability, repairing barriers, and facilitat -\ning skin proliferation by penetrating beneath the stratum \ncorneum. A local inflammatory process was observed \nin the skin among subjects with magnesium deficiency \n[14], and aa cross-sectional study showed that there \nwas a direct association between severity of vulgaris \nacne and magnesium level [48]; however, the evidence \nis equivocal. Two clinical trials reported the impact of \nmagnesium containing drugs/supplements on acne. Nev -\nertheless, these studies administered magnesium in com -\nbination with other components and drugs. One study \nused liposomal magnesium in combination with folic \nacid and topical antibiotic and found that this interven -\ntion resulted in improvement of acne[16]. Another study \ninvolved 252 adults with acne and used a magnesium-\ncontaining medication[49]. Acne severity was improved \nafter using a magnesium-containing drug. It showed that \nmagnesium may have beneficial effects on acne. Since \nmagnesium was not used by itself in these studies, we \ncould not conclude that magnesium was the main cause \nof acne improvement.\nWe found that magnesium supplementation had no \nsignificant effect on alopecia. We hypothesized that mag-\nnesium supplementation may improve alopecia because \nprevious studies showed that magnesium deficiency con -\ntributed to alopecia and disrupted cholesterol-enhanced \nhair loss [50]. Also, topical application of magnesium \nwas reported to be effective in regrowth of shed hair in \nmice [51]. Nevertheless, a case–control study found that \nonly protein intake was directly effective in alopecia com-\npared to micronutrients including magnesium [52]. Also, \na meta-analysis revealed that magnesium deficiency was \nnot a risk factor of hair loss [53].\nWe did not observe any significant change in AUB after \nmagnesium supplementation. Although some previous \nstudies evaluated the efficacy of magnesium supplemen -\ntation in PCOS, its effect on AUB was not assessed, or \ndue to publication bias and adverse outcomes, results \nremain unpublished. Therefore, we could not compare \nour findings with previous results.\nIn this study, magnesium supplementation resulted in \nimprovement of physical function and physical health \nin women with PCOS. According to previous studies, \nphysical activity is associated with increased magne -\nsium requirement and intake [54]. Also, during physi -\ncal activity, sweating and cell peeling reduce magnesium \nlevel [55]. Moreover, there are potential beneficial effects \nof magnesium supplementation on muscle metabolism \nand favorable physical function, including improved car -\ndiorespiratory and leg muscle function [56, 57], lower \nserum total creatine kinase activity, and skeletal muscle \ncreatine kinase isoenzyme [58].\nMagnesium supplementation in women with PCOS \nimproved emotional and mental aspects of quality of life. \nPrevious studies showed that low magnesium intake was \nsignificantly associated with externalizing behaviors [59], \nwhilst another study found an inverse relationship between \ndietary magnesium intake and incidence of depression \n[17]. A review study asserted favorable effects of magne -\nsium supplementation on different types of mental dis -\norder including depressive symptoms, anxiety disorders, \nattention deficit hyperactivity disorder, autism, obsessive–\ncompulsive disorder, and eating disorders [60]. The antide-\npressant effect of magnesium is mediated by a variety of \nmechanisms; indeed, magnesium blocks the N-methyl-D-\naspartate glutamatergic receptor, whilst other components \nof glutamatergic transport, such as the AMPA α-amino-3-\nhydroxy-5-methyl-4-isoxazole propionic acid receptor, is \nmodified by magnesium [61]. Elevated brain magnesium \nlevels may increase fear memory retention by increas -\ning N‐methyl‐D‐aspartate signaling, brain-derived neu -\nrotrophic factor expression, and synaptic plasticity in the \nbody. Therefore, magnesium may increase mental aspects \nof quality of life by its antidepressant effect.\nIn the present study, an improvement in the general \nhealth of patients with PCOS was observed after magne -\nsium supplementation. Since magnesium is a coenzyme \n\nPage 9 of 11\nJaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n \nof more than 300 enzymes in the body, and many chemi -\ncal reactions require sufficient magnesium level, it is \nunsurprising that the general health of the body depends \non adequate intake of magnesium [62]. In clinical prac -\ntice, optimizing magnesium status through diet and sup -\nplements appears to be a safe, useful, and documented \ntreatment for several diseases [63]. Therefore, magne -\nsium supplementation may have a beneficial effect on \nimproving physical, mental, and general health of the \nbody and thus a better quality of life in patients with \nPCOS. Therefore, according to previous observations and \nthe results of this study, magnesium supplementation can \nplay an effective role in improving the total quality of life.\nSeveral strengths and limitations should be stated with \nregard to the present study. the Covid-19 pandemic and \nsubsequent lockdown was a reason for several partici -\npants ceasing study enrolment. In addition, some vari -\nables in the present study were collected by subjective \nmethods, which is often accompanied by recall bias; \nhowever, we utilized validated methods in an effort to \nameliorate this issue. A strength of the current study was \nusing ITT method in statistical analysis, which was a pri -\nori defined. Also, all components of quality of life were \nreported in the results, allowing detailed insight into \nnumerous aspects of quality of life.\nConclusion\nMagnesium supplementation in women with PCOS had \na significant positive effect on improving total quality \nof life and its components. However, data regarding the \neffect of magnesium supplementation on alopecia, AUB \nand acne was not sufficient to draw a consensual conclu -\nsion. Future studies should assess the effect of magne -\nsium supplementation on AUB, acne and alopecia.\nSupplementary Information\nThe online version contains supplementary material available at https:// doi. \norg/ 10. 1186/ s12958‑ 022‑ 00982‑7.\nAdditional file 1. \nAcknowledgements\nNone\nAuthors’ Contribution\nG.A and M.H.R and H.G formulated hypothesis and designed the study. M.J, \nM.G and H.G administered supplements and collected data. M.H.R analyzed \ndata. C.C.T.C and M.J interpreted results and wrote the manuscript. All authors \nrevised manuscripts. All authors read and approved the final manuscript.\nFunding\nThis study was supported by Isfahan University of Medical science. The \nfunders had no role in the study design, data collection, and analysis, decision \nto publish, or preparation of the manuscript.\nAvailability of data and materials\nData will be available on request.\nDeclarations\nTransparency Declaration\nThe lead author affirms that this manuscript is an honest, accurate, and trans‑\nparent account of the study being reported. The reporting of this work is com‑\npliant with CONSORT guidelines. The lead author affirms that no important \naspects of the study have been omitted and that any discrepancies from the \nstudy as planned. The Research Council and Ethical Committee of Isfahan Uni‑\nversity of Medical Sciences, Isfahan, Iran and Food Security Research Center, \nIsfahan University of Medical Sciences, Isfahan, Iran approved this study (Code: \nIR.MUI.RESEARCH.REC.1399.406). This randomized clinical trial was registered at \nIRCT.ir on 2020–10‑18 (Registration Code: IRCT20130903014551N9).\nEthics approval and consent to participate\nThis study was ethically approved by The Research Council and Ethical \nCommittee of Isfahan University of Medical Sciences, Isfahan, Iran, (Code: \nIR.MUI.RESEARCH.REC.1399.406), and was registered at IRCT.ir on 2020–10‑18 \n(Registration Code: IRCT20130903014551N9). Also, all participants completed \nan informed consent form.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare that they have no competing interests.\nAuthor details\n1 Food Security Research Center and Department of Community Nutrition, \nSchool of Nutrition and Food Science, Isfahan University of Medical Sciences, \nIsfahan, Iran. 2 Infertility & IVF Fellowship, Department of Obstetrics and Gyne‑\ncology, Isfahan University of Medical Sciences, Isfahan, Iran. 3 Centre for Intel‑\nligent Healthcare, Coventry University, Coventry CV1 5FB, UK. \nReceived: 24 April 2022   Accepted: 24 July 2022\nReferences\n 1. Dunaif A. Hyperandrogenic anovulation (PCOS): A unique disorder of \ninsulin action associated with an increased risk of non‑insulin‑dependent \ndiabes mellitus. Am J Med. 1995;98(1 SUPPL.1):33S‑39S.\n 2. Okoroh EM, Hooper WC, Atrash HK, Yusuf HR, Boulet SL. Prevalence of \npolycystic ovary syndrome among the privately insured, United States, \n2003–2008. Am J Obstet Gynecol. 2012;207(4):299.e1‑299.e7.\n 3. Livadas S, Diamanti‑Kandarakis E. Polycystic ovary syndrome: Definitions, \nphenotypes and diagnostic approach. In: Polycystic OvarySyndrome: \nNovel Insights into Causes and Therapy. Front Horm Res. 2013;40:1–21 S. \nKarger AG.\n 4. Goldzieher JW, Green JA. The polycystic ovary. I. Clinical and histologic \nfeatures. J Clin Endocrinol Metab. 1962;22:325–38. https:// doi. org/ 10. \n1210/ jcem‑ 22‑3‑ 325.\n 5. Cela E, Robertson C, Rush K, Kousta E, White DM, Wilson H, et al. Preva‑\nlence of polycystic ovaries in women with androgenic alopecia. Eur J \nEndocrinol. 2003;149(5):439–42.\n 6. Archer JS, Chang RJ. Hirsutism and acne in polycystic ovary syndrome. \nBest Pract Res Clin Obstet Gynaecol. 2004;18(5):737–54.\n 7. Walton S, Cunliffe WJ, Keczkes K, Early AS, McGarrigle HH, Katz M, et al. \nClinical, ultrasound and hormonal markers of androgenicity in acne \nvulgaris. Br J Dermatol. 1995;133(2):249–53.\n 8. Jones GL, Palep‑Singh M, Ledger WL, Balen AH, Jenkinson C, Campbell \nMJ, et al. Do South Asian women withPCOS have poorer health‑related \nquality of life than Caucasian women with PCOS?A comparative cross‑\nsectional study. Health Qual Life Outcomes. 2010;8:149.\n 9. Benson S, Hahn S, Tan S, Mann K, Janssen OE, Schedlowski M, et al. Preva‑\nlence and implications of anxiety in polycystic ovary syndrome: results of \nan internet‑based survey in Germany. Hum Reprod. 2009;24(6):1446–51.\n 10. O’driscoll K, O’gorman DM, Taylor S, Boyle LA. The influence of amagne‑\nsium‑rich marine extract on behaviour, salivary cortisol levels and skinle‑\nsions in growing pigs. Animal. 2013;7(6):1017–27.\n\nPage 10 of 11Jaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n 11. Parazzini F, Di Martino M, Pellegrino P . Magnesium in the gynecological \npractice: a literature review. Magnes Res. 2017;30(1):1–7. English. https:// \ndoi. org/ 10. 1684/ mrh. 2017. 0419.\n 12. Seifert B, Wagler P , Dartsch S, Schmidt U, Nieder J. [Magnesium–a new \ntherapeutic alternative in primary dysmenorrhea]. Zentralbl Gynakol. \n1989;111(11):755–60.\n 13. Goluch‑koniuszy ZS. Nutrition of women with hair loss problem during \nthe period of menopause. Prz Menopauzalny. 2016;15(1):56–61.\n 14. Chandrasekaran NC, Weir C, Alfraji S, Grice J, Roberts MS, Barnard RT. \nEffects of magnesium deficiency–more than skin deep. Exp Biol Med \n(Maywood). 2014;239(10):1280–91.\n 15. Koshel MV, Chebotarev VV. ACNE Treatment in patients with connective \ntissue dysplasia. Med News North Caucasus. 2014;9(2):170–2.\n 16. Fabbrocini G, Donnarumma M, Russo G, Marasca C, Savastano S, Barrea \nL, et al. Effectiveness of supplementation with myo‑inositol, folic acid \nand liposomal magnesium in male insulin‑resistant patients with acne. \nEsperienze Dermatol. 2016;18(2):76–9.\n 17. Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A. Asso‑\nciation between magnesium intake and depression and anxiety in \ncommunity‑dwelling adults: the Hordaland Health Study. Aust N Z J \nPsychiatry [Internet]. 2009 Jan [cited 2019 Dec 14];43(1):45–52. Available \nfrom: http:// www. ncbi. nlm. nih. gov/ pubmed/ 19085 527\n 18. Yary T, Lehto SM, Tolmunen T, Tuomainen TP , Kauhanen J, Voutilainen \nS, et al. Dietary magnesium intake and the incidence of depression: A \n20‑year follow‑up study. J Affect Disord. 2016;15(193):94–8.\n 19. Parazzini F, Di Martino M, Pellegrino P . Magnesium in the gynecological \npractice: a literature review. Magnes Res. 2017;30(1):1–7.\n 20. Tarleton EK, Littenberg B, MacLean CD, Kennedy AG, Daley C. Role of \nmagnesium supplementation in the treatment of depression: A rand‑\nomized clinical trial. PLoS One. 2017;12(6):e0180067.\n 21. Ibáñez L, Oberfield SE, Witchel S, Auchus RJ, Chang RJ, Codner E, et al. An \nInternational Consortium Update: Pathophysiology, Diagnosis, and Treat‑\nment of Polycystic Ovarian Syndrome in Adolescence. Horm Res Paediatr. \n2017;88(6):371–95.\n 22. Teede H, Misso M, Costello M, Dokras A, Laven J, Moran L, et al. Interna‑\ntional evidence‑based guideline for the assessment and management of \npolycystic ovary syndrome 2018. Melbourne, Australia: Monash Univer‑\nsity; 2018.\n 23. Behboodi Moghadam Z, Fereidooni B, Saffari M, Montazeri A. Polycystic \novary syndrome and its impact on Iranian women’s quality of life: A \npopulation‑based study. BMC Womens Health. 2018;18(1):164.\n 24. Munro MG, Critchley HOD, Broder MS, Fraser IS. FIGO classification system \n(PALM‑COEIN) for causes of abnormal uterine bleeding in nongravid \nwomen of reproductive age. Int J Gynecol Obstet. 2011;113(1):3–13.\n 25. Fraser IS, Critchley HOD, Broder M, Munro MG. The FIGO recommenda‑\ntions on terminologies and definitions for normal and abnormal uterine \nbleeding. Semin Reprod Med. 2011;29(5):383–90.\n 26. Fabbrocini G, Cantelli M, Masarà A, Annunziata MC, Marasca C, Cac‑\nciapuoti S. Female pattern hair loss: A clinical, pathophysiologic, and \ntherapeutic review. Int J Womens Dermatol. 2018;4(4):203–11 Elsevier Inc.\n 27. Khoshdel A, Shekari A, Paydary K, Shekari I. Alopecia Areata: The Role of \nStressful Events and an Estimate of Lifetime Risk in First‑Degree Relatives. \nJ Arch Mil Med. 2016;4(1):e36377. https:// doi. org/ 10. 5812/ jamm. 36377.\n 28. Sinclair R, Torkamani N, Jones L. Androgenetic alopecia: New insights \ninto the pathogenesis and mechanism of hair loss. F1000Research. \n2015;4(August):1–10.\n 29. Ramli R, Malik AS, Hani AFM, Jamil A. Acne analysis, grading and \ncomputational assessment methods: An overview. Ski Res Technol. \n2012;18(1):1–14.\n 30. Hanisah AH, Omar K, Shah SA. Prevalence of acne and its impact on the \nquality of life in school‑aged adolescents in Malaysia. J Prim Health Care. \n2009;1(1):20–5.\n 31. Elham B, Somayeh S, Afsaneh S, Azadeh G, Mohammadreza G, Saba S, \nMasoomeh R. The effect of metformin in the treatment of intractable \nand late onset acne: a comparison with oral isotretinoin. Iran J Derma‑\ntol. 2019;22(2):47–52. https:// doi. org/ 10. 22034/ ijd. 2019. 98371.\n 32. Li Y, Li Y, Yu Ng EH, Stener‑Victorin E, Hou L, Wu T, et al. Polycystic ovary \nsyndrome is associated with negatively variable impacts on domains of \nhealth‑related quality of life: Evidence from a meta‑analysis. Fertil Steril. \n2011;96(2):452–8.\n 33. Bazarganipour F, Ziaei S, Montazeri A, Foroozanfard F, Kazemnejad A, \nFaghihzadeh S. Health‑related quality of life in patients with polycystic \novary syndrome (PCOS): A model‑based study of predictive factors. J Sex \nMed. 2014;11(4):1023–32.\n 34. Tajvar M, Arab M, Montazeri A. Determinants of health‑related quality of \nlife in elderly in Tehran. Iran BMC Public Health. 2008;8(1):1–8.\n 35. Montazeri A, Goshtasebi A, Vahdaninia M, Gandek B. The Short Form \nHealth Survey (SF‑36): Translation andvalidation study of the Iranian ver‑\nsion. Quality of Life Research. 2005;14:875–82.\n 36. Ware JE Jr, Gandek B. Overview of the SF‑36 Health Survey and the \nInternational Quality of Life Assessment (IQOLA) Project. J Clin Epidemiol. \n1998;51(11):903–12. https:// doi. org/ 10. 1016/ s0895‑ 4356(98) 00081‑x.\n 37. Ware JE. SF‑36 Health Survey update. Spine. 2000;25:3130–9.\n 38. Xi W, Pennell ML, Andridge RR, Paskett ED. Comparison of intent‑to‑treat \nanalysis strategies for pre‑post studies with loss to follow‑up. Contemp \nClin Trials Commun [Internet]. 2018 Sep;11:20–9. Available from: https:// \nlinki nghub. elsev ier. com/ retri eve/ pii/ S2451 86541 73019 41\n 39. Ching HL, Burke V, Stuckey BGA. Quality of life and psychological morbid‑\nity in women with polycystic ovary syndrome: Body mass index, age \nand the provision of patient information are significant modifiers. Clin \nEndocrinol (Oxf ). 2007;66(3):373–9.\n 40. Coffey S, Bano G, Mason HD. Health‑related quality of life in women with \npolycystic ovary syndrome: A comparison with the general population \nusing the Polycystic Ovary Syndrome Questionnaire (PCOSQ) and the \nShort Form‑36 (SF‑36). Gynecol Endocrinol. 2006;22(2):80–6.\n 41. Drosdzol A, VSBMRP‑C. Quality of life and marital sexual satisfaction \nin women with polycystic ovary syndrome. Folia Histochem Cytobiol. \n2007;45(Suppl 1):S93‑7.\n 42. Pirnia B, Masoudi R, Pirnia K, Jalali M, Eslami MR, Malekanmehr P , et al. \nEffect of Magnesium Sulfate Added to Tincture of Opium and Buprenor‑\nphine on Pain and Quality of Life in Women with Dysmenorrhea: A \nProspective, Randomized, Double‑blind. Placebo‑controlled Trial Addict \nHeal. 2020;12(4):259–68.\n 43. Engen DJ, McAllister SJ, Whipple MO, Cha SS, Dion LJ, Vincent A, et al. \nEffects of transdermal magnesium chloride on quality of life for patients \nwith fibromyalgia: a feasibility study. J Integr Med. 2015;13(5):306–13.\n 44. Ezhov AV, Pimenov LT. [Effect of adjuvant magnesium therapy on the \nquality of life and emotional status of elderly patients with stable angina]. \nAdv Gerontol. 2002;10:95–8.\n 45. Kazaks AG, Uriu‑Adams JY, Albertson TE, Shenoy SF, Stern JS. Effect of \noral magnesium supplementation on measures of airway resistance and \nsubjective assessment of asthma control and quality of life in men and \nwomen with mild to moderate asthma: A randomized placebo controlled \ntrial. J Asthma. 2010;47(1):83–92.\n 46. Zaenglein AL, Graber EM, Thiboutot DM. Chapter 80. Acne Vulgaris and \nAcneiform Eruptions. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, \nLeffell DJ, Wolff K. eds. Fitzpatrick’s Dermatology in General Medicine, \n8e. McGraw Hill; 2012. https:// acces smedi cine. mhmed ical. com/ conte nt. \naspx? bookid= 392& secti onid= 41138 785. Accessed 31 July 2022. \n 47. Barratt H, Hamilton F, Car J, Lyons C, Layton A, Majeed A. Outcome meas‑\nures in acne vulgaris: systematic review. Br J Dermatol. 2009;160(1):132–6.\n 48. Tamara A, Anggowarsito JL, Tandyono V. ASSOCIATION BETWEEN MAG‑\nNESIUM LEVELS AND THE SEVERITY OF ACNE VULGARIS. J WIDYA Med Jr. \n2021;3(4):237–41.\n 49. Marina K, Vyacheslav C. Acne treatment in patients with connective \ntissue dysplasia. Meдицинcкий вecтник Ceвepнoгo Кaвкaзa. 2014;9(2 \n(34)):170–2.\n 50. Sadgrove NJ. The ‘bald’ phenotype (androgenetic alopecia) is caused \nby the high glycaemic, high cholesterol and low mineral ‘western diet.’ \nTrends Food Sci Technol. 2021;116:1170–8.\n 51. Shanmugam S, Baskaran R, Nagayya‑Sriraman S, Yong CS, Choi HG, Woo \nJS, et al. The effect of methylsulfonylmethane on hair growth promotion \nof magnesium ascorbyl phosphate for the treatment of alopecia. Biomol \nTher. 2009;17(3):241–8.\n 52. El Fékih N, Kamoun H, Fazaa B, El Ati J, Zouari B, Kamoun MR, et al. Evalu‑\nation of the role of dietary intake in the occurrence of alopecia. Rev Med \nLiege. 2010;65(2):98–102.\n 53. Jin W, Zheng H, Shan B, Wu Y. Changes of serum trace elements \nlevel in patients with alopecia areata: A meta‑analysis. J Dermatol. \n2017;44(5):588–91.\n\nPage 11 of 11\nJaripur et al. Reproductive Biology and Endocrinology          (2022) 20:110 \n \n•\n \nfast, convenient online submission\n •\n  \nthorough peer review by experienced researchers in your field\n• \n \nrapid publication on acceptance\n• \n \nsupport for research data, including large and complex data types\n•\n  \ngold Open Access which fosters wider collaboration and increased citations \n \nmaximum visibility for your research: over 100M website views per year •\n  At BMC, research is always in progress.\nLearn more biomedcentral.com/submissions\nReady to submit y our researc hReady to submit y our researc h  ?  Choose BMC and benefit fr om: ?  Choose BMC and benefit fr om: \n 54. Lukaski HC. Magnesium, zinc, and chromium nutriture and physical activ‑\nity. Am J Clin Nutr. 2000;72(2):585S‑593S.\n 55. Chandra RK. Progress in food and nutrition science. Nut Res. 1986;6:473 \nElsevier.\n 56. Ripari P , Pieralisi G, Giamberardino MA, Vecchiet L. Effects of magnesium \npicolinate on some cardiorespiratory submaximal effort parameters. \nMagnes Res. 1989;2:70–4.\n 57. Brilla LR, Haley TF. Effect of magnesium supplementation on strength \ntraining in humans. J Am Coll Nutr. 1992;11(3):326–9.\n 58. Golf S, Bender S, Grüttner J. On the Significance of Magnesium in Extreme \nPhysical Stress. Cardiovasc Drugs Ther. 1998;12:197–202. https:// doi. org/ \n10. 1023/A: 10077 08918 683.\n 59. Black LJ, Allen KL, Jacoby P , Trapp GS, Gallagher CM, Byrne SM, et al. Low \ndietary intake of magnesium is associated with increased externalising \nbehaviours in adolescents. Public Health Nutr. 2015;18(10):1824–30.\n 60. Botturi A, Ciappolino V, Delvecchio G, Boscutti A, Viscardi B, Brambilla P . \nThe role and the effect of magnesium in mental disorders: a systematic \nreview. Nutrients. 2020;12(6):1661.\n 61. Pochwat B, Szewczyk B, Sowa‑Kucma M, Siwek A, Doboszewska U, Pieko‑\nszewski W, et al. Antidepressant‑like activity of magnesium in the chronic \nmild stress model in rats: alterations in the NMDA receptor subunits. Int J \nNeuropsychopharmacol. 2014;17(3):393–405.\n 62. Dreosti IE. Magnesium status and health. Nutr Rev. 1995;53(9):S23.\n 63. Schwalfenberg GK, Genuis SJ. The Importance of Magnesium in Clinical \nHealthcare. Scientifica (Cairo) [Internet]. 2017;2017:4179326. Available \nfrom: http:// www. ncbi. nlm. nih. gov/ pubmed/ 29093 983\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in pub‑\nlished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}