Effects of boron supplementation on the severity and duration of pain in primary dysmenorrhea; Complementary Therapies in Clinical Practice, 2015; Link

Considering Boron's purported anti-inflammatory properties, this triple-blind randomized clinical trial aimed to assess Boron supplementation's effects on menstrual pain severity and duration in female university students. Recruiting 113 participants, matched for dysmenorrhea severity and duration, they were randomly assigned to case (n=58) and control (n=55) groups. The case group received 10 mg/day Boron from two days before menstruation until its third day, while the control group received placebo capsules. Pain severity and duration were measured at baseline and over two menstrual cycles. Results showed significantly lower pain severity and duration in the Boron group post-intervention compared to controls (P < 0.05). The study suggests that Boron supplementation may alleviate menstrual pain by exerting anti-inflammatory effects, warranting further research to explore its hormonal and inflammatory biomarker effects in dysmenorrhea. 

Calcium supplementation, both alone and combined with vitamin D, significantly improves symptoms of premenstrual syndrome (PMS) in women. Clinical trials demonstrate that calcium effectively alleviates key PMS symptoms such as fatigue, appetite changes, and depression.

Effects of calcium supplement therapy in women with premenstrual syndrome; Taiwanese Journal of Obstetrics and Gynecology, 2009; Link

The study aimed to assess the efficacy of calcium supplementation in alleviating premenstrual syndrome (PMS) symptoms. Conducted as a double-blind clinical trial, it involved young female college students diagnosed with PMS. Participants were divided into two groups: one received a placebo, while the other received 500 mg of calcium carbonate twice daily for three months. Symptom severity, including early fatigability, appetite changes, and depression, was evaluated using a standard questionnaire before and after treatment. The findings revealed that the group treated with calcium supplements experienced significant improvements in early tiredness, appetite changes, and depressive symptoms compared to the placebo group. The study concluded that calcium supplementation effectively reduces key symptoms of PMS in women, highlighting its potential as a therapeutic option for managing PMS.

Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome; International Journal of Gynecology & Obstetrics, 2009; Link

The study aimed to evaluate and compare the efficacy of dydrogesterone and calcium plus vitamin D supplementation in alleviating severe premenstrual syndrome (PMS) symptoms. Conducted as a randomized, double-blind, placebo-controlled trial, it involved 180 Shiraz University students diagnosed with PMS. Participants documented their symptoms over two menstrual cycles, then were randomly assigned to receive either 5 mg dydrogesterone, 500 mg calcium plus 200 IU vitamin D, or a placebo, taken twice daily from the 15th to the 24th day of their menstrual cycle for two additional cycles. Symptom severity was assessed using questionnaires during the intervention. The results indicated that both dydrogesterone and calcium plus vitamin D supplementation similarly reduced PMS symptom severity (by 4.64% and 4.20% respectively), compared to a 3.42% decrease observed with placebo treatment. The conclusion drawn from these findings is that dydrogesterone and calcium plus vitamin D offer comparable benefits in reducing PMS symptoms, suggesting either treatment could be considered as an option for managing severe PMS.

A systematic review of the role of vitamin D and calcium in premenstrual syndrome; Obstetrics & Gynecology Science, 2019; Link

This systematic review assessed the impact of calcium and vitamin D on premenstrual syndrome (PMS) by analyzing 28 high-quality articles from various databases. It found that low serum levels of these nutrients during the luteal phase may contribute to PMS symptoms. Supplementation or dietary intake of calcium and vitamin D was recommended as an effective, low-risk, and cost-efficient approach to alleviate PMS symptoms, highlighting their significance in managing this common disorder among women of reproductive age. 

Calcium carbonate and the premenstrual syndrome: effects on premenstrual and menstrual symptoms. Premenstrual Syndrome Study Group; American Journal of Obstetrics and Gynecology, 1998; Link 

The study aimed to assess the impact of calcium carbonate on premenstrual syndrome (PMS) symptoms during the luteal and menstrual phases of the menstrual cycle. It was a prospective, randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial involving healthy, premenopausal women aged 18 to 45 years from 12 outpatient centers across the United States. Participants, who had moderate-to-severe cyclically recurring premenstrual symptoms, were documented over two menstrual cycles using a daily rating scale with 17 core symptoms and 4 symptom factors (negative affect, water retention, food cravings, and pain). Participants were randomized to receive either 1200 mg of elemental calcium per day in the form of calcium carbonate or a placebo for three menstrual cycles. The primary outcome measured was the symptom complex score across 17 parameters. Out of 720 women screened, 497 were enrolled, and 466 were included in the efficacy analysis. The study found no significant differences between groups in demographic characteristics or baseline symptom scores. However, during the treatment phase, the calcium-supplemented group showed significantly lower mean symptom complex scores in the second and third treatment cycles compared to placebo, with a 48% overall reduction in total symptom scores by the third cycle, compared to a 30% reduction in the placebo group. All four symptom factors showed significant improvements by the third treatment cycle in the calcium group. The study concludes that calcium supplementation is an effective and simple treatment for PMS, significantly reducing overall luteal phase symptoms.

Recent studies reveal dark chocolate may reduce menstrual pain and anxiety in late adolescents. Trials involving herbal ingredient combinations and music alongside dark chocolate showed effective pain alleviation, underscoring its potential as a beneficial intervention for dysmenorrhea.

Dark chocolate's effect on menstrual pain in late adolescents; Belitung Nursing Journal, 2017; Link

This study focused on the impact of dark chocolate on menstrual pain among late adolescents, employing a randomized pretest-posttest control group design. Conducted from September to November 2016 at Bhakti Husada Boarding School of Poltekkes Kemenkes Semarang, 50 participants were divided equally into experimental and control groups through simple random sampling. Pain levels were assessed using the Numeric Rate Scale (NRS), and statistical analyses, including the independent t-test and Mann-Whitney test, were applied to evaluate the intervention's effectiveness. The findings revealed a significant reduction in menstrual pain levels in the group that received dark chocolate (mean pain level of 2.76) compared to the control group (mean pain level of 5.36), with a p-value of less than 0.001. The study concludes that dark chocolate significantly alleviates menstrual pain in late adolescents.

Effect of Combination of Dark Chocolate and Herbal Ingredients for Dysmenorrhea in Late Adolescents; Journal of Tropical Pharmacy and Chemistry, 2023; Link

This study investigated the efficacy of dark chocolate combined with herbal ingredients (turmeric, red ginger, moringa, sambiloto extract, and honey) in reducing menstrual pain among 30 respondents divided into three groups: a positive control group (K), a dark chocolate group (C), and a group receiving a combination of dark chocolate with herbs (C+H). The combination was administered as a 250 mL beverage. Utilizing a quasi-experimental design, the study quantitatively measured pain using the Numeric Rating Scale (NRS) before and 2 hours after the intervention. The results indicated a significant reduction in menstrual pain in the group receiving the dark chocolate and herbs combination (p < 0.05), leading to the conclusion that this mixture could be an effective therapy for dysmenorrhea.

The effect of dark chocolate and music on pain and anxiety in young women with primary dysmenorrhea: Randomized controlled trial; European Journal of Integrative Medicine, 2022; Link

This study assessed the effectiveness of music and dark chocolate in reducing pain and anxiety associated with primary dysmenorrhea (PD) among young women. In a non-blinded, randomized controlled trial, 90 nulliparous nursing students aged 18–25 with PD and a Visual Analog Scale (VAS) pain score of 5 or higher were divided into three groups: dark chocolate, music, and control. The study concluded with 84 participants due to dropouts. The intervention involved consuming dark chocolate for three days before and on the first day of menstruation, and listening to music for the same duration in the respective groups. Pain intensity and anxiety were measured using VAS and the State-Trait Anxiety Inventory (STAI) before and after the interventions. Results showed a significant reduction in menstrual pain and anxiety in the dark chocolate and music groups, with no notable changes in the control group. The study suggests that both dark chocolate and music can effectively alleviate menstrual pain and anxiety, indicating potential as nursing interventions for PD. Further research is suggested to solidify these findings.

Associations of menstrual pain with intakes of soy, fat and dietary fiber in Japanese women; European Journal of Clinical Nutrition, 2005; Link

In a cross-sectional study of 276 Japanese women aged 19-24 from three colleges and two nursing schools, researchers investigated the relationship between dietary intake and menstrual pain severity. They found that higher dietary fiber intake was significantly associated with reduced menstrual pain (r=−0.12, P=0.04) after adjusting for age, smoking status, age at menarche, and total energy intake. However, intakes of soy and fat did not show a significant correlation with menstrual pain severity. The study suggests that while the link between dietary fiber and menstrual pain is modest, it merits further investigation to understand its potential for managing dysmenorrhea.

Magnesium supplementation has shown promising results in the management of premenstrual syndrome (PMS) and primary dysmenorrhea, offering significant relief from symptoms such as mood changes, pain, and fluid retention.

Comparisons between magnesium and oral contraceptives highlight magnesium's efficacy in decreasing pelvic pain and the need for analgesics, although not as effectively as contraceptives. Studies further indicate magnesium's role in alleviating PMS-related mood and physical symptoms, with effects notable from the second cycle of administration.

The broad applicability of magnesium in gynecological health, including dysmenorrhea and PMS, underscores its potential as a non-invasive treatment option. Further research is encouraged to explore its full therapeutic benefits and optimal dosing strategies.

Investigation of Laboratory and Clinical Features of Primary Dysmenorrhea: Comparison of Magnesium and Oral Contraceptives in Treatment; Cureus, 2022; Link

GPT This prospective case-controlled study aimed to explore the characteristics of primary dysmenorrhea (PD) patients and compare the efficacy of 200 mg magnesium citrate (MgS) versus combination oral contraceptive (COC) therapy in treating PD. Involving 172 women with PD and a control group of 172 age-matched women without PD, the study divided PD patients into two treatment groups: one receiving 200 mg MgS and the other COC therapy. The Visual Analogue Scale (VAS) measured dysmenorrhea severity at baseline and after three months of treatment. Key findings include PD patients exhibiting more menstrual bleeding, a higher incidence of maternal dysmenorrhea, lower serum calcium, and vitamin D levels compared to controls. Post-treatment, the COC group showed significantly lower VAS scores and reduced need for painkillers compared to the MgS group. However, MgS treatment significantly decreased pelvic pain and the need for painkillers in PD patients, though not as effectively as COC therapy. The study highlights lower serum calcium and vitamin D levels in PD and indicates both MgS and COC as valuable treatments, with COC being more effective in reducing pain and analgesic use.

Oral magnesium successfully relieves premenstrual mood changes; Obstetrics And Gynecology, 1991; Link

GPT This study evaluated the effects of magnesium (Mg) supplementation on premenstrual syndrome (PMS) symptoms in 32 women. Using a double-blind, randomized design, participants received either Mg or a placebo from the 15th day of their menstrual cycle until menstruation began, over two cycles. Results indicated significant improvements in PMS symptoms, particularly in mood changes, for those receiving Mg. Additionally, Mg levels increased in certain white blood cells but not in plasma or erythrocytes. The findings suggest Mg supplementation could be an effective treatment for mood-related PMS symptoms. 

Therapeutic effects of magnesium in dysmenorrhea; Schweiz Rundsch Med Prax, 1990; Link 

This randomized double-blind study evaluated magnesium's effects on primary dysmenorrhea in 32 women, analyzing results from 21 participants. Magnesium treatment slightly improved symptoms on the first day but significantly reduced back and lower abdominal pain on the second and third days of the menstrual cycle. The study also noted a marked decrease in work absences due to dysmenorrhea among those receiving magnesium. These findings suggest potential benefits of magnesium for dysmenorrhea, warranting further investigation in multicenter studies.

Magnesium supplementation alleviates premenstrual symptoms of fluid retention; Journal of Women's Health, 1998; Link

This study assessed the impact of a 200 mg daily magnesium oxide (MgO) supplement on premenstrual symptoms (PMS) severity through a randomized, double-blind, placebo-controlled, crossover trial. Over two menstrual cycles, 38 women took either the MgO supplement or a placebo, recording their symptoms across six categories (anxiety, craving, depression, hydration-related symptoms, other, and total symptoms) using a 4-point scale in a 22-item menstrual diary. The effectiveness of the magnesium supplementation was evaluated by comparing symptoms' severity and urinary magnesium output. The findings indicated that magnesium supplementation did not significantly affect any symptom category during the first month. However, in the second month, there was a notable reduction in hydration-related symptoms (PMS-H) such as weight gain, swelling of extremities, breast tenderness, and abdominal bloating with magnesium supplementation compared to the placebo (p = 0.009). Compliance with the supplementation regimen was confirmed through increased urinary magnesium output during the magnesium supplementation phase compared to the placebo phase (p = 0.013), with mean outputs of 100.8 mg and 74.1 mg, respectively. The study concludes that a daily supplement of 200 mg of magnesium oxide can reduce mild premenstrual symptoms related to fluid retention by the second cycle of administration.

Magnesium in the gynecological practice: a literature review; Magnesium Research, 2017; Link

This research systematically reviewed the evidence on the effectiveness of oral magnesium supplementation in treating various gynecological conditions, exploring its pharmacological mechanisms. The findings reveal that magnesium supplementation is beneficial in preventing and managing conditions such as dysmenorrhea (painful menstruation), premenstrual syndrome (PMS), menstrual migraines, and symptoms associated with menopause (climacteric symptoms). This suggests that magnesium plays a significant role in gynecological health, offering a non-invasive option for mitigating these common yet impactful conditions.

Pilot study of the efficacy and safety of a modified-release magnesium 250 mg tablet (Sincromag) for the treatment of premenstrual syndrome; Clinical Drug Investigation, 2007; Link

GPT This open-label study explored the efficacy and safety of a patented modified-release magnesium 250 mg tablet in alleviating premenstrual syndrome (PMS) symptoms in women. Over three months, 41 women aged 18-45 with regular menstrual cycles and diagnosed with PMS (based on a PMS questionnaire score of ≥25) received the magnesium tablet from 20 days post-menstruation to the onset of their next period. The study found significant improvements in PMS symptoms, with the mean total PMS score, as determined by Moos' Modified Menstrual Distress Questionnaire, significantly decreasing after three months of treatment (p < 0.0001). Similarly, patient diaries reported substantial improvements across all subscales. The treatment led to a 35.1% reduction in total PMS scores according to investigators, and a 33.5% reduction according to patient assessments. The magnesium tablet was well-tolerated, with only one reported case of vertigo as a treatment-related side effect. The study concludes that modified-release magnesium is effective in reducing PMS symptoms, offering a promising treatment option for women with PMS.

These studies collectively highlight the significant role of dietary patterns in the management and risk of premenstrual syndrome (PMS) and primary dysmenorrhea. Western diets high in fast foods and processed meats are associated with increased PMS risk, while traditional and healthy diets, as well as whole grain and Mediterranean diet adherence, offer protective effects. Nutritional interventions, including increased consumption of fruits, vegetables, fish, and whole grains, show promise in alleviating symptoms.

Conversely, dieting for weight loss during adolescence and meal skipping are linked to worse menstrual pain, underscoring the importance of balanced eating habits. The complex relationship between specific dietary fats and PMS suggests that further research is needed to fully understand the nutritional influences on menstrual health.

Dietary patterns are associated with premenstrual syndrome: evidence from a case-control study; Public Health Nutr, 2020; Link

The study investigated how diet affects Premenstrual Syndrome (PMS), identifying three main dietary patterns among participants: Western (fast foods, soft drinks, processed meats), Traditional (eggs, tomato sauce, fruits, red meat), and Healthy (dried fruits, condiments, nuts). Findings showed that the Western diet increased PMS risk, while Traditional and Healthy diets were associated with a lower risk. This suggests that dietary choices play a significant role in the management of PMS symptoms.

Nutrition as a Potential Factor of Primary Dysmenorrhea: A Systematic Review of Observational Studies; Gynecol Obstet Invest, 2019; Link

The study reviewing nutritional factors influencing primary dysmenorrhea found that increased consumption of fruits, vegetables, fish, milk, and dairy products is associated with reduced menstrual pain, highlighting the potential benefits of these foods in managing symptoms. Conversely, meal skipping and diets aimed at weight loss were linked to increased severity of dysmenorrhea, suggesting the importance of regular and balanced eating habits for women experiencing menstrual pain. However, due to methodological inconsistencies across studies, the findings are inconclusive, underscoring the need for further research with more robust methodologies to clarify the impact of diet on dysmenorrhea.

Diets enriched with whole grains reduce premenstrual syndrome scores in nurses: an open-label parallel randomised controlled trial; Br J Nutr, 2019; Link

This clinical trial investigated the impact of whole grain consumption on Premenstrual Syndrome (PMS) symptoms among 100 nurses diagnosed with PMS, divided into intervention and control groups of fifty each. The intervention group replaced at least four servings of refined grains with whole grains daily for three months, consuming 120g of bread made from whole flour, while the control group continued their usual grain intake. Results indicated a significant reduction in general, mood, physical, and behavioral PMS symptoms in the intervention group compared to the control group, demonstrating the potential benefits of whole grains in alleviating PMS symptoms. This study highlights the need for further research to confirm these promising findings.

Diet during adolescence is a trigger for subsequent development of dysmenorrhea in young women; Int J Food Sci Nutr, 2007; Link

The study conducted among 716 female students aged 18 to 20 years at Ashiya College in Japan explored the relationship between dietary habits and menstrual disorders, focusing on the impact of dieting for cosmetic purposes. The participants were categorized based on their dieting experience: Group I (no dieting experience), Group II (currently dieting), and Group III (history of dieting). The analysis revealed that individuals in Group II exhibited a higher frequency of irregular menstruation compared to the other groups. Additionally, Group III experienced a more intense level of dysmenorrhea (menstrual pain) than their counterparts. These findings indicate that dietary restrictions during adolescence can have detrimental long-term effects on reproductive health in young women, underscoring the importance of promoting healthy eating habits among this demographic.

The effect of diet on primary dysmenorrhea in university students: A randomized controlled clinical trial. Pak J Med Sci, 2018; Link

The study aimed to assess the effectiveness of diet therapy on alleviating primary dysmenorrhea symptoms among female university students. Employing a randomized controlled pre- and post-test design, 67 students suffering from primary dysmenorrhea were divided into two groups: a diet therapy group and a control group. The intensity of dysmenorrhea was measured using the Visual Analogue Scale and a modified questionnaire that evaluated various symptoms associated with dysmenorrhea. The intervention group underwent diet therapy for three months, with assessments conducted before the intervention and three months afterward. Initially, there was no significant difference in the mean intensity of dysmenorrhea between the two groups. However, post-intervention results showed a notable reduction in dysmenorrhea intensity in the diet therapy group compared to the control group, indicating that diet therapy effectively reduced pain associated with primary dysmenorrhea among the participants. This suggests that dietary adjustments could be a viable approach to managing primary dysmenorrhea symptoms in female university students.

Association among Premenstrual Syndrome, Dietary Patterns, and Adherence to Mediterranean Diet; Nutrients, 2022; Link

The study explored the relationship between dietary patterns, adherence to the Mediterranean diet (MD), and the prevalence of Premenstrual Syndrome (PMS) among Korean women. Conducted through an online survey, 262 women aged 20-49 years were assessed for PMS using the American College of Obstetricians and Gynecologists diagnostic criteria. The adherence to the MD was evaluated using the Korean version of the Mediterranean Diet Adherence Screener, with Mediterranean Diet Scores (MDS) categorized into tertiles. Findings indicated that women with the lowest adherence to the MD (T1: 0-3 points) reported a significantly higher prevalence of PMS compared to those with the highest adherence (T3: ≥6 points), highlighting a potential protective effect of the MD against PMS. Additionally, a dietary pattern characterized by high consumption of bread and snacks was associated with an increased risk of PMS, suggesting that dietary habits may play a critical role in the management and prevention of PMS symptoms. This study underscores the importance of dietary choices in influencing PMS among Asian women, particularly highlighting the potential benefits of adhering to a Mediterranean diet.

Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II; Br J Nutr. 2017; Link

This study explored the link between dietary fat intake and the development of Premenstrual Syndrome (PMS) within a subset of the Nurses' Health Study II cohort. It contrasted the experiences of 1,257 women with clinician-diagnosed PMS against 2,463 controls who had minimal or no premenstrual symptoms. Dietary intake, including total fats, specific fat subtypes, and fatty acids, was assessed through food frequency questionnaires. The findings revealed no association between the intake of total fat, monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), and trans fats with the onset of PMS after adjusting for confounding factors such as age, BMI, smoking, and calcium intake. Interestingly, a high intake of saturated fatty acids (SFA) was linked to a reduced risk of PMS. This association was primarily driven by stearic acid intake, suggesting that individuals in the highest quintile of stearic acid consumption had a lower risk of developing PMS compared to those in the lowest quintile. The study concluded that general fat consumption does not contribute to a higher risk of PMS, and a high intake of stearic acid might even lower the risk. However, it suggests that further prospective research is needed to confirm these findings, highlighting the complexity of dietary influences on PMS symptoms.

This collection of research highlights the significant benefits of iron supplementation in nonanemic menstruating women with low ferritin, showing reduced fatigue and improved iron status without notable changes in quality of life or mood disorders. Additionally, an association between iron depletion, menstruation, and dietary habits in adolescent girls suggests a critical need for targeted nutritional strategies to mitigate iron deficiency risks.

Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial; Canadian Medical Association Journal, 2012; Link

This multicenter, parallel, randomized controlled trial investigated the impact of oral iron therapy on fatigue, quality of life, and certain blood markers in nonanemic iron-deficient women with unexplained fatigue. Conducted across 44 primary care practices in France from March to July 2006, the study involved 198 women aged 18-53 years, who were not anemic but exhibited ferritin levels below 50 μg/L and hemoglobin levels above 12.0 g/dL. Participants were randomly assigned to receive either 80 mg of elemental iron daily (n=102) or a placebo (n=96) for 12 weeks. The primary outcome was the change in fatigue, measured by the Current and Past Psychological Scale. Results indicated a significant reduction in fatigue scores by 47.7% in the iron group compared to 28.8% in the placebo group, with no significant changes in quality of life, depression, or anxiety levels. Iron supplementation led to significant increases in hemoglobin and ferritin levels and a decrease in soluble transferrin receptor levels at 12 weeks. This suggests that iron supplementation can be beneficial for nonanemic menstruating women with ferritin levels below 50 μg/L experiencing unexplained fatigue, with recommendations to assess treatment efficacy through blood markers after six weeks.

Daily iron supplementation for improving anaemia, iron status and health in menstruating women; Cochrane Database of Systematic Reviews, 2016; Link

This systematic review and meta-analysis aimed to assess the effects of daily iron supplementation on anaemia, iron status, and various health aspects in menstruating women. The comprehensive search across multiple databases and digital thesis repositories in November 2015 resulted in the inclusion of 67 trials, encompassing 8506 women. The findings indicate that iron supplementation significantly reduces the risk of anaemia and iron deficiency, and increases haemoglobin concentration compared to control groups. However, the review also highlights the increased risk of gastrointestinal side effects, including loose stools/diarrhoea and constipation, associated with iron supplementation. Despite these side effects, iron supplementation did not significantly impact adherence rates. The evidence on the improvement of cognitive function was inconclusive, though supplementation did improve exercise performance and reduce fatigue. Overall, daily iron supplementation is effective in reducing anaemia and iron deficiency, enhancing haemoglobin levels and exercise performance, and mitigating fatigue in menstruating women, albeit with an increased risk of gastrointestinal symptoms.

Iron requirements in menstruating women; The American Journal of Clinical Nutrition, 1991; Link

This study recalculates the daily iron requirements for adult and teenage menstruating women, incorporating variations in menstrual blood losses, hemoglobin levels, basal iron losses, and growth requirements for teenagers. The revised daily iron needs are estimated at 2.84 mg for adult women and 3.21 mg for teenagers, reflecting the 95th percentiles for these groups. To determine dietary iron requirements based on these absorbed iron needs, six assessments of whole-diet iron bioavailability were conducted, considering diets from Sweden, France, and the US. These estimations suggest a dietary iron bioavailability ranging from 14% to 16.6%, with a standardized figure of 15% being proposed for the bioavailability of iron in a typical Western diet. Consequently, the dietary iron requirements to meet the 95th percentiles for absorbed iron are set at 18.9 mg per day for adult menstruating women and 21.4 mg per day for menstruating teenagers, assuming no existing iron stores.

Association of Iron Depletion with Menstruation and Dietary Intake Indices in Pubertal Girls: The Healthy Growth Study; BioMed Research International 2013; Link

This study explored the relationship between iron depletion (ID), menstrual blood loss, and lifestyle factors, including diet and physical activity, among 1222 girls aged 9–13 years. It found that 33.5% of adolescent girls with menses were iron depleted (serum ferritin < 12 μg/L), compared to 15.9% of girls without menses. Iron-depleted girls without menses consumed less poultry but more fruits and fast food than their non-iron-depleted counterparts. Multivariate logistic regression analysis revealed that girls with menses were significantly more likely to be iron depleted, with menstruation being a key factor increasing the risk of ID. Additionally, ID was associated with dietary habits, such as high calcium intake, frequent fast food consumption, and low poultry and fruit intake. The study underscores the need for further research to better understand the impact of diet and menstruation on iron status in pubertal girls, highlighting the importance of addressing nutritional needs and menstrual blood loss in this vulnerable group.

Omega-3 fatty acid supplementation has been consistently shown to reduce premenstrual symptoms, improve quality of life, and alleviate dysmenorrhea pain in women of reproductive age. Studies ranging from randomized clinical trials to systematic reviews and meta-analyses highlight the potential of omega-3s in managing symptoms of premenstrual syndrome and primary dysmenorrhea, with significant reductions in symptom severity and analgesic use.

While the effectiveness of treatment may vary with dosage, age, and possibly individual metabolic differences, the evidence supports omega-3 supplements as a beneficial, low-risk approach for enhancing women's health and well-being related to menstrual discomfort. These findings suggest a promising non-pharmacological option for women experiencing discomfort due to menstrual symptoms, although further research is encouraged to explore the mechanisms and long-term effects.

The effect of omega 3 fatty acid supplementation on premenstrual syndrome and health-related quality of life: a randomized clinical trial; Journal of Psychosomatic Obstetrics & Gynecology, 2018; Link

This study aimed to explore the effects of omega-3 supplements on premenstrual symptoms and quality of life in reproductive-aged women. Conducted as a randomized clinical trial with 95 Iranian participants aged 20-35, the study found that omega-3 supplementation significantly reduced premenstrual symptoms and improved overall quality of life. These findings suggest that omega-3 supplementation could be a promising approach for managing premenstrual symptoms and enhancing women's well-being.

Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents; American Journal of Obstetrics and Gynecology, 1996; Link

The study aimed to investigate the potential of dietary omega-3 fatty acid supplementation in alleviating dysmenorrhea symptoms among adolescents. Forty-two participants were randomly assigned to two groups, receiving either fish oil or a placebo for two months each. Results showed a significant reduction in the Cox Menstrual Symptom Scale after two months of fish oil treatment compared to baseline (p < 0.0004), suggesting a beneficial effect of omega-3 fatty acids on dysmenorrhea symptoms in adolescents.

The impact of omega-3 polyunsaturated fatty acids on primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials; European Journal of Clinical Pharmacology, 2022; Link

The present study showed that n-3 PUFAs could have a mild effect on the severity of primary dysmenorrhea in women. Furthermore, the highest effectiveness of treatment was seen at low doses of n-3 PUFAs, and with increasing daily intake, the effectiveness of treatment with n-3 PUFAs decreased. Another finding indicated that with the increasing age of women, n-3 PUFAs showed lesser effectiveness in reducing the severity of primary dysmenorrhea. The results of the present study provide valuable evidence to primary healthcare providers and health policymakers in the treatment of primary dysmenorrhea.

Omega-3 long chain polyunsaturated fatty acids as a potential treatment for reducing dysmenorrhoea pain: Systematic literature review and meta-analysis; Nutrition & Dietetics, 2024; Link

This systematic literature review with meta-analysis aimed to assess the impact of omega-3 long chain polyunsaturated fatty acids on prostaglandin levels and pain severity in women with dysmenorrhea, while also identifying potential adverse side effects. Conducting searches across multiple databases, twelve studies involving 881 dysmenorrheal women were analyzed, with predominantly neutral quality. Results indicated that daily supplementation of 300-1800 mg omega-3 long chain polyunsaturated fatty acids over 2-3 months significantly reduced dysmenorrhea pain, as demonstrated by a large effect size in the meta-analysis. Although most studies did not measure prostaglandin levels, a majority reported decreased analgesic use with omega-3 supplementation, and few reported mild adverse effects. Despite these positive outcomes, the neutral quality of the research and unresolved mechanisms of action underscore the need for further investigation in this area.

Effect of omega-3 fatty acids on intensity of primary dysmenorrhea; International Journal of Gynecology & Obstetrics, 2012; Link

In a study targeting women aged 18-22 with primary dysmenorrhea, researchers conducted a double-blind crossover investigation to determine the efficacy of omega-3 fatty acid supplementation in alleviating symptoms. Divided into two groups, participants received either omega-3 capsules or placebos for three months, followed by a switch for another three months, with a washout period in between. Results indicated a significant reduction in pain intensity after omega-3 treatment, along with a decreased requirement for rescue doses of ibuprofen compared to the placebo group. These findings suggest that dietary supplementation with omega-3 fatty acids holds promise in reducing primary dysmenorrhea symptoms and diminishing reliance on pain relief medication.

The significant shift from the evolutionary omega-6/omega-3 ratio of close to 1:1 in human diets to today's Western diet, often exceeding 15/1, underscores the dietary imbalance contributing to the pathogenesis of chronic diseases like cardiovascular disease, cancer, and inflammatory conditions.

This discrepancy emphasizes the need for increased omega-3 intake, which has shown suppressive effects on these conditions. Furthermore, the interplay between dietary fatty acids and genetic variations, such as those in the 5-lipoxygenase gene, highlights the complexity of chronic disease manifestation and the importance of a balanced omega-6/omega-3 ratio for disease prevention and management. Achieving a lower omega-6/omega-3 ratio is crucial for mitigating the risk of prevalent chronic diseases in Western societies and beyond, pointing to the need for dietary adjustments tailored to individual genetic backgrounds and specific health conditions.

The importance of the ratio of omega-6/omega-3 essential fatty acids; Biomed Pharmacother., 2002; Link

Various sources suggest that human evolution favored a diet with an omega-6 to omega-3 essential fatty acid ratio close to 1, contrasting sharply with today's Western diets, which often exceed a ratio of 15/1 to 16.7/1. This dietary imbalance, deficient in omega-3 fatty acids and abundant in omega-6 fatty acids, contributes to the pathogenesis of numerous diseases, including cardiovascular disease, cancer, and inflammatory conditions. Conversely, higher omega-3 intake has suppressive effects on these diseases. Studies demonstrate that different diseases require different optimal omega-6/omega-3 ratios, suggesting a multifactorial and multigenic nature of chronic diseases. Thus, achieving a lower ratio of omega-6/omega-3 fatty acids is crucial for reducing the risk of chronic diseases prevalent in Western societies and globally.

Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases; Biomed Pharmacother., 2006; Link

Anthropological and molecular evidence highlights that humans evolved on a diet with an omega-6 to omega-3 ratio close to 1, contrasting sharply with today's Western diets, which often exceed a ratio of 15/1 to 16.7/1. This dietary imbalance promotes various diseases, including cardiovascular diseases, cancer, and inflammatory conditions, while higher omega-3 intake suppresses inflammation. Genetic variations, like those in the 5-lipoxygenase (5-LO) gene, influence disease manifestation and response to dietary fatty acids. Maintaining a balanced omega-6/omega-3 ratio is crucial for preventing and managing chronic diseases, with optimal ratios varying depending on genetic factors and specific health conditions.

Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride.; National Academies Press (US), 1997; Link

Phosphorus is abundantly available in the diet, with its bioavailability affected by factors like food processing and dietary components. Despite its wide availability, attention to dietary intake is necessary to prevent imbalances that could impact health indirectly through effects on energy production, bone health, and overall physiological well-being.

The research highlights Vitamin B1's significant role in mitigating premenstrual syndrome (PMS) symptoms, demonstrating that supplementation can substantially reduce both mental and physical aspects of PMS.

This finding is supported by broader nutritional studies indicating that higher dietary intake of thiamin (Vitamin B1) and riboflavin is linked to a reduced risk of developing PMS. Together, these studies suggest that Vitamin B1, along with other B vitamins, could be a safe and effective approach for managing PMS symptoms, offering an alternative to those seeking non-pharmacological treatment options.

The Effects of Vitamin B1 on Ameliorating the Premenstrual Syndrome Symptoms; Glob J Health Sci., 2014; Link

This study investigated the impact of Vitamin B1 on premenstrual syndrome (PMS) symptoms among students at Jahrom University of Medical Sciences dormitories in 2013. In this double-blind placebo-controlled trial, 80 students were divided into Vitamin B1 and placebo groups. Symptoms of PMS were recorded before and during the intervention. Results showed that Vitamin B1 significantly reduced both mental (35.08%) and physical (21.2%) symptoms of PMS, with notable improvements compared to the placebo group. The study concludes that Vitamin B1 effectively alleviates mental and physical symptoms of PMS, suggesting it as a viable, side-effect-free treatment option for managing PMS symptoms. 

Micronutrient Intake and Premenstrual Syndrome; Dissertation, University of Massachusetts Amherst, 2011; Link

This study found that high thiamin and high riboflavin intake from food sources were associated with lower risk of PMS.

Treatment of depression: time to consider folic acid and vitamin B12; British Association for Psychopharmacology, 2005; Link

The review highlights significant findings linking low levels of folate and vitamin B12 with major depression. Studies indicate that depressive patients often have low serum or red blood cell folate and vitamin B12, a trend also observed in the general population. Interestingly, regions with diets rich in folate, like Hong Kong and Taiwan, show higher serum folate levels even among depressive patients and lower lifetime rates of major depression. Additionally, low folate levels are associated with a poorer response to antidepressants, but supplementation with folic acid can enhance antidepressant efficacy. Similarly, a high vitamin B12 status may lead to a better treatment outcome. The review also mentions the MTHFR C677T polymorphism, which affects homocysteine metabolism and is more common among depressive patients, further strengthening the link between these vitamins and depression. Based on these findings, the review suggests that oral supplementation of folic acid (800 µg daily) and vitamin B12 (1 mg daily) could potentially improve treatment outcomes for depression.

Micronutrient Intake and Premenstrual Syndrome; Dissertation, University of Massachusetts Amherst, 2011; Link

This study found that high thiamin and high riboflavin intake from food sources were associated with lower risk of PMS.

Pyridoxine (vitamin B6) therapy for premenstrual syndrome; International Journal of Gynecology & Obstetrics, 2007; Link

In a double-blind, randomized, controlled trial with 160 university students experiencing premenstrual syndrome (PMS), 94 participants fully complied with the trial's protocol. They were divided into two groups: one received pyridoxine (vitamin B6) and the other a placebo, both manufactured to be indistinguishable in shape, color, and taste. Over two menstrual cycles, after an initial three cycles of symptom recording, participants took an 80 mg daily tablet of either pyridoxine or placebo and continued to log their symptoms. The study found no significant difference in the number of symptoms or the severity of PMS between the two groups at the outset. However, after treatment, both groups saw a decrease in symptoms such as moodiness, irritability, anxiety, depression, and others, with anxiety showing the most significant reduction. The decrease in symptoms was more substantial in the pyridoxine group, especially for psychiatric symptoms, suggesting that pyridoxine could be an effective treatment for the psychiatric symptoms of PMS.

Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review; BMJ, 1999; Link

This study systematically reviews randomized placebo-controlled trials to assess Vitamin B-6's effectiveness in managing premenstrual syndrome (PMS). Analyzing data from nine trials involving 940 patients, it found that Vitamin B-6 significantly improved overall PMS symptoms, with an odds ratio of 2.32 (95% CI, 1.95 to 2.54) compared to placebo. Additionally, Vitamin B-6 showed benefits in alleviating premenstrual depressive symptoms, with an odds ratio of 1.69 (95% CI, 1.39 to 2.06) across four trials with 541 patients. However, the study notes the overall low quality of the included trials and suggests that Vitamin B-6 doses up to 100 mg/day may help treat PMS symptoms and depression, though more high-quality research is needed for a definitive conclusion.

A Pilot Randomized Treatment-Controlled Trial Comparing Vitamin B6 with Broad-Spectrum Micronutrients for Premenstrual Syndrome; Journal of Alternative and Complementary Medicine, 2020; Link

In a study comparing the effectiveness of a broad-spectrum micronutrient formula to Vitamin B6 for treating PMS, 78 women participated in a three-cycle treatment following a two-cycle baseline. Both treatments significantly reduced PMS symptoms, with 72% of the micronutrient group and 60% of the B6 group showing full remission. The micronutrient formula also improved quality of life more than B6, particularly for participants with severe symptoms indicative of premenstrual dysphoric disorder (PMDD), although these findings need further research for confirmation. No serious adverse effects were reported from either treatment.

High-dose vitamin D supplementation significantly reduces the prevalence and symptoms of PMS and dysmenorrhea among adolescents, suggesting a potent strategy for managing these conditions.

Systematic reviews confirm that calcium and vitamin D play crucial roles in reducing PMS symptoms, recommending them as effective, low-risk treatments. Furthermore, vitamin D supplementation in adolescents with severe hypovitaminosis D has demonstrated substantial improvements in PMS-related mood disorders.

Additionally, vitamin D supplementation effectively reduces pain and systemic symptoms in women with primary dysmenorrhea and vitamin D deficiency, highlighting its potential as a non-pharmacological treatment option.

These findings underscore the importance of considering vitamin D and calcium supplementation as part of a comprehensive approach to managing PMS and dysmenorrhea.

Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome; International Journal of Gynecology & Obstetrics, 2009; Link

The study aimed to evaluate and compare the efficacy of dydrogesterone and calcium plus vitamin D supplementation in alleviating severe premenstrual syndrome (PMS) symptoms. Conducted as a randomized, double-blind, placebo-controlled trial, it involved 180 Shiraz University students diagnosed with PMS. Participants documented their symptoms over two menstrual cycles, then were randomly assigned to receive either 5 mg dydrogesterone, 500 mg calcium plus 200 IU vitamin D, or a placebo, taken twice daily from the 15th to the 24th day of their menstrual cycle for two additional cycles. Symptom severity was assessed using questionnaires during the intervention. The results indicated that both dydrogesterone and calcium plus vitamin D supplementation similarly reduced PMS symptom severity (by 4.64% and 4.20% respectively), compared to a 3.42% decrease observed with placebo treatment. The conclusion drawn from these findings is that dydrogesterone and calcium plus vitamin D offer comparable benefits in reducing PMS symptoms, suggesting either treatment could be considered as an option for managing severe PMS.

High dose vitamin D supplementation can improve menstrual problems, dysmenorrhea, and premenstrual syndrome in adolescents; Gynecological Endocrinology, 2018; Link

This study evaluated the effects of high-dose vitamin D supplementation on dysmenorrhea and premenstrual syndrome (PMS) in 897 adolescent girls in Mashhad and Sabzevar, Iran. Participants received nine weekly doses of 50,000 IU of cholecalciferol (vitamin D3) over 9 weeks. The study categorized participants into four groups: those with only PMS, those with only dysmenorrhea, those with both conditions, and normal subjects without these conditions. The findings revealed a significant reduction in PMS prevalence, from 14.9% to 4.8% (p < .001), after vitamin D supplementation. The prevalence of dysmenorrhea also decreased slightly from 35.9% to 32.4%, and the incidence among subjects with both PMS and dysmenorrhea reduced from 32.7% to 25.7%. Moreover, the supplementation led to a decrease in several PMS symptoms, such as backache and a tendency to cry easily, and a reduction in the pain severity of dysmenorrhea (p < .05). The study concluded that high-dose vitamin D supplementation could effectively reduce the prevalence of PMS and dysmenorrhea, alongside improving both physical and psychological symptoms associated with PMS.

A systematic review of the role of vitamin D and calcium in premenstrual syndrome; Obstetrics & Gynecology Science, 2019; Link

This systematic review assessed the impact of calcium and vitamin D on premenstrual syndrome (PMS) by analyzing 28 high-quality articles from various databases. It found that low serum levels of these nutrients during the luteal phase may contribute to PMS symptoms. Supplementation or dietary intake of calcium and vitamin D was recommended as an effective, low-risk, and cost-efficient approach to alleviate PMS symptoms, highlighting their significance in managing this common disorder among women of reproductive age.

Vitamin D Supplementation for Premenstrual Syndrome-Related Mood Disorders in Adolescents with Severe Hypovitaminosis D; Journal of Pediatric and Adolescent Gynecology, 2016; Link

This study aimed to evaluate the effectiveness of vitamin D supplementation in young girls (15-21 years old) with severe hypovitaminosis D and premenstrual syndrome (PMS), particularly focusing on mood disorders. A total of 158 participants with severe PMS symptoms and low serum levels of 25-hydroxycholecalciferol (≤10 ng/mL) were randomly assigned to receive either vitamin D (200,000 IU initially, followed by 25,000 IU biweekly for 4 months; group 1, n=80) or a placebo (group 2, n=78). The study assessed the clinical and hormonal effects of the treatment. Results showed that in the vitamin D group, serum levels reached the normal range (35-60 ng/mL) within the first month and remained stable. Significant improvements were observed in anxiety, irritability, ease of crying, sadness, and disturbed relationships scores, with no significant changes in the placebo group. The frequency of adverse events, including nausea and constipation, was similar between the two groups. The conclusion drawn from the study is that vitamin D supplementation is a safe, effective, and convenient treatment for improving the quality of life in young women with severe hypovitaminosis D and mood disorders associated with PMS.

Vitamin D supplementation for primary dysmenorrhea: a double-blind, randomized, placebo-controlled trial; Obstetrics & Gynecology Science, 2021; Link 

The study aimed to assess the impact of vitamin D supplementation on pain and systemic symptoms in female students aged 18 to 32 years with primary dysmenorrhea and vitamin D deficiency. In this double-blind, randomized, placebo-controlled trial, 116 participants were divided into two groups, receiving either 50,000 IU of vitamin D3 (cholecalciferol) or a placebo weekly for eight weeks. The evaluation focused on pain intensity, days with pain, consumption of pain-relief medications, and severity of systemic symptoms such as fatigue, headache, nausea/vomiting, and diarrhea. The results demonstrated that participants who received vitamin D supplements showed significant improvements in all measured outcomes. There was a notable decrease in pain intensity, fewer days with pain, reduced consumption of pain-relief medications, and a decrease in the severity of systemic symptoms at both the 4-week and 8-week marks, with all changes being statistically significant (P<0.001). No significant improvements were observed in the placebo group. The conclusion drawn from the study is that vitamin D supplementation can effectively reduce pain intensity, decrease the number of days with pain, lessen the need for pain-relief medications, and improve systemic symptoms in women with primary dysmenorrhea and vitamin D deficiency.

These studies demonstrate the effectiveness of zinc sulfate and zinc supplementation in alleviating symptoms of primary dysmenorrhea and premenstrual syndrome (PMS) in young women and female university students. Zinc supplementation can improve both physical and psychological PMS symptoms, enhances quality of life, and may offer anti-inflammatory, antioxidant, and antidepressant benefits, indicating their potential as cost-effective treatments for these conditions.

Comparison of the effect of ginger and zinc sulfate on primary dysmenorrhea: a placebo-controlled randomized trial; Pain Manag Nurs., 2014; Link

This randomized trial aimed to assess the efficacy of ginger and zinc sulfate compared to a placebo in alleviating the severity of primary dysmenorrhea among young women. The study involved 150 high school students who were divided into three groups to receive either ginger capsules, zinc sulfate capsules, or placebo capsules for four days, starting the day before the onset of menstruation until the third day of menstrual bleeding. The severity of dysmenorrhea was measured every 24 hours using the pain visual analog scale. Results showed that both ginger and zinc sulfate significantly reduced pain severity compared to the placebo, with both treatments having similar effectiveness in improving the symptoms of primary dysmenorrhea. This indicates that ginger and zinc sulfate can serve as effective treatments for managing pain associated with primary dysmenorrhea in young women.

The Effect of Zinc Supplementation on the Improvement of Premenstrual Symptoms in Female University Students: a Randomized Clinical Trial Study; Biological Trace Element Research, 2023; Link

This study aimed to assess the impact of zinc supplementation on premenstrual symptoms among female university students compared to a placebo. In this triple-masked, randomized, placebo-controlled trial, 69 students aged 18-35 with premenstrual syndrome (PMS), residing in dormitories at Hamadan University of Medical Sciences in Iran, were evenly divided into two groups. One group received 220 mg of elemental zinc daily for 24 weeks, while the control group was given a placebo. The evaluation of PMS was conducted using the Premenstrual Symptoms Screening Tool-Adolescent (PSST-A) questionnaire. Statistical analysis was performed using SPSS version 16, employing Chi-square and t-student tests to compare outcomes between the groups. Results showed significant improvements in both physical and psychological symptoms of PMS in the zinc group compared to the placebo, including reductions in anger, anxiety, depression, overeating, breast tenderness, headaches, muscle pain, bloating, and weight gain. Additionally, relationships with friends, classmates, and coworkers significantly improved in the zinc group. The findings suggest zinc supplementation as a potential, cost-effective treatment for alleviating PMS symptoms, although further research is needed to confirm these results.

Effect of zinc sulfate supplementation on premenstrual syndrome and health-related quality of life: Clinical randomized controlled trial;  The Journal Of Obstetrics And Gynaecology Research, 2017; Link

This study aimed to evaluate the impact of zinc sulfate (ZS) supplementation on premenstrual syndrome (PMS) symptoms and health-related quality of life (QoL) in women aged 20-35. Conducted as a double-blind randomized, placebo-controlled trial, 142 women with PMS were divided into two groups to receive either 220-mg ZS capsules, containing 50 mg elemental zinc, from the 16th day of their menstrual cycle until the second day of the next cycle, or a placebo. The effectiveness of the treatment was measured using the Premenstrual Symptoms Screening Tool (PSST) and the 12-item Short-Form Health Survey Questionnaire. Results showed a significant decrease in moderate to severe PMS prevalence in the ZS group over three months, with noticeable improvements in PSST scores and both physical and mental components of QoL. However, significant QoL improvements were only observed three months post-intervention. This suggests that zinc sulfate could be an effective, low-cost treatment for PMS symptoms and enhancing health-related QoL, although further research is needed to confirm these findings.

Effect of Zinc Supplementation on Physical and Psychological Symptoms, Biomarkers of Inflammation, Oxidative Stress, and Brain-Derived Neurotrophic Factor in Young Women with Premenstrual Syndrome: a Randomized, Double-Blind, Placebo-Controlled Trial; Biological Trace Element Research, 2020; Link

This study investigates the impact of zinc supplementation on young women with premenstrual syndrome (PMS), focusing on its potential anti-inflammatory, antioxidant, and antidepressant benefits. Conducted as a randomized, double-blind, placebo-controlled trial, 60 women aged 18-30 diagnosed with PMS were divided into two groups to receive either 30 mg of zinc gluconate or a placebo for 12 weeks. Results showed that zinc supplementation significantly reduced both physical and psychological PMS symptoms, increased total antioxidant capacity and brain-derived neurotrophic factor, but had no significant effect on high sensitivity reactive protein. The findings suggest that 12 weeks of zinc supplementation can have beneficial effects on PMS symptoms, antioxidant capacity, and neurotrophic factors in young women.