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| REVIEW ARTICLE |
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| Year : 2022 | Volume
: 7
| Issue : 1 | Page : 19-26 |
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A review on the efficacy of fish oil and its components in alleviating the symptoms of primary dysmenorrhea
Shreyasi Roy
Department of Anthropology, University of North Bengal, Raja Rammohunpur, Darjeeling, West Bengal, India
| Date of Submission | 29-Nov-2021 |
| Date of Decision | 22-Jan-2022 |
| Date of Acceptance | 29-Jan-2022 |
| Date of Web Publication | 27-Jun-2022 |
Correspondence Address:
Shreyasi Roy
Department of Anthropology, University of North Bengal, NBU Campus, Raja Rammohunpur, Darjeeling, West Bengal
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/bjhs.bjhs_128_21
Periods are part of normal sexual health for women during their reproductive years. In addition to various social and religious stigmas during those “bad stains” days, period cramps (also called dysmenorrhea) accompany us to make the situation worse. Studies have showered numerous data regarding various pharmacological interventions (PIs) and non-pharmacological interventions (non-PIs). Non-PIs have been preferred mostly in cases where PIs are contraindicated. Fish oil supplements or omega-3 supplements are one of the safest non-PIs. The present study attempted to conduct a review of the existing literature to illustrate the aptness and potentiality of fish oil in easing period cramps.
Keywords: Dysmenorrhea, fish oil, omega-3, period cramps
How to cite this article:
Roy S. A review on the efficacy of fish oil and its components in alleviating the symptoms of primary dysmenorrhea. BLDE Univ J Health Sci 2022;7:19-26 |
Period cramp (or rather dysmenorrhea) is cited as painful menstrual cramps of uterine origin. Dysmenorrhea is a common gynecological complaint whose prevalence varies between 16% and 91% in women of reproductive age, with severe pain observed in 2% to 29%.[1] The severe pain engenders recurrent short-term absenteeism from school and work. Moreover, this is associated with significant impairment in quality of life among 16%–29% of women.[1]
Dysmenorrhea could be divided into primary (which involves the absence of any discernible macroscopic pelvic pathology) and secondary (which involves the presence of anatomic or macroscopic pelvic pathology) dysmenorrhea.[2] The detailed pathophysiology of primary dysmenorrhea (PD) is yet to be studied. One of the dominant contributing physiological factors unearthed is increased amounts of prostaglandins present in the menstrual fluid.[2] Increased synthesis of prostaglandins induces strong contractions of the uterus which eventually leads to menstrual cramps, abdominal discomfort along with other symptoms such as lower back pain, nausea, vomiting, fatigue, headache, dizziness, irritability, etc.
Proctor and Farquhar framed a detailed log of several pharmacological interventions (PIs) (such as simple analgesics, nonsteroidal anti-inflammatory drugs [NSAIDs], cyclooxygenase-2 [COX 2]-specific inhibitors, oral contraceptives, levonorgestrel-releasing intrauterine system, combined drug therapy, etc.) and non-PIs (NPIs) (such as herbal products/medicines, dietary supplements, heat, acupuncture, acupressure, dietary changes, physical exercise, spinal manipulation, etc.) that had been used to reduce the menstrual pain.[3] The use of NPIs was observed to be lesser compared to PIs because of ignorance, substandard integration in the society and health professionals, lack of trust, limited and inconsistent evidence on the effectiveness of NPIs. On second thought, NPIs should be favored more because of the following reasons:
- NPIs offer more options compared to PIs
- NPIs have less or no serious side effects
- Many patients often do not respond well to PIs.
| How can Fish Oil Help us? | |  |
The protective effects of fish oils were first reported by Bang, et al. who observed that ischemic heart disease was quite rare among Greenlandic Eskimos despite their intake of saturated animal fats.[4] Fish oil supplements (or, omega-3 supplements) are one of the NPIs which proved to be quite effective in treating PD as depicted by several studies. The blockage of prostaglandins synthesis is a major mechanism of fish oil. The protective role of fish (oil) is due to the content of omega-3 (or, n-3) fatty acids. The contents of omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) possess anti-inflammatory properties which eventually aid to lessen several body pain including menstrual cramps. On the flip side, eicosanoids derived from omega-6 fatty acids such as arachidonic acid (AA) possess proinflammatory and immunoactive functions.[5] Dietary omega-3 fatty acids penetrate the phospholipid membranes and inhibit the formation of omega-6-derived eicosanoids. Prostaglandins produced from omega-3 fatty acids are less potent and can turn down the contraction of the myometrium and blood vessels.[6] The great amount of EPA in the diet is also assumed to yield a decreased production of pro-inflammatory eicosanoids of prostaglandin E2 and prostaglandin F2α and increased production of prostacyclin (PGI2), which further enhances myometrium relaxation.[7] The health benefits of omega-3 fatty acids in terms of biochemical pathways had been best demonstrated in several studies.[8]
There has been no attempt to date to synthesize the available pieces of evidence for the efficacy of fish oil in alleviating PD. The purpose of the present review was to systematically evaluate all the available pieces of evidence on the efficacy of fish oil in alleviating PD. To the best of the author's knowledge, this is the second review on the effectiveness of fish oil in attenuating PD. Before this, a meta-analysis involving six studies was published recently which too attempted to establish whether fish oil could aid in reducing PD.[9]
| Methods for Literature Search | | |
The study was conducted from the period of March 15, 2021 to October 31, 2021. This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Circumstantial information on studies of fish oil as a remedy for dysmenorrhea was acquired from various peer-reviewed indexed journals abstracted in various databases such as PubMed® (Medline), POPLINE, Cochrane Library, and Trip Database. In addition, the search was also done through various grey literature sources, namely OpenGrey, Google Scholar, and Google. The following keywords have been used for the literature search both independently and in combination:
- Menstrual pain fish oil
- Dysmenorrhea fish oil omega-3 marine
- Menstrual discomfort supplements
- Menstrual cramp period fish oil
- Dysmenorrhoea dietary supplements.
Available full-text articles and abstracts were screened. A thorough search in various databases mentioned above using the aforementioned keywords and in-depth scrutiny over the references lists of those publications retrieved altogether 125 publications till October 2021 [Figure 1]. Out of the initial searches, 70 studies have been excluded since they do not meet specific selection criteria. This stage of selection left out 55 studies for further analysis. Out of the remaining 55 studies, 32 studies have been eliminated owing to being duplicate references. Ultimately, 23 studies (both abstracts and full-text papers) have been selected for final analysis. Care was taken to omit those studies which involved premenstrual syndrome and endometriosis (and not PD) since there is a strict difference between PD, endometriosis and pre-menstrual syndrome.[10],[11] | Figure 1: Modified preferred reporting items for systematic reviews and meta-analyses flow diagram of literature search
Click here to view |
| Results of the Literature Search | | |
The main data and findings of the selected studies were framed in [Table 1] (cross-over trials) and [Table 2] (other clinical trials). Out of the 23 selected studies, 17 were conducted in Iran. A higher number of such studies in Iran could be probably because this country has an acute prevalence of PD (0.71 [95% confidence interval [CI]: 0.65, 0.77]).[35]
Out of 23 studies, 7 were crossover trials [Table 1]. Majority of the reported trials were placebo-controlled. The clinical trials exhibited a clear comparison between the efficacy of fish oil (or omega-3) supplements and that of Mefenamic acid, Rosa damascena extracts, Ibuprofen dose, acupressure, Vitamin B1, B12, E, and calcium supplementation.
The subjects chosen for the selected studies were single, of adolescent and/or reproductive age, suffering from mild, moderate, and severe PD. The ethnicity of the participants was not vividly mentioned in any of the selected studies. Nearly all the studies (except one[27]) permitted the subjects to consume rescue medications in case of severe pain during the experimental protocol.
The severity and duration of pain were assessed through Visual Analog Scaling, McGill pain ruler, Cox Menstrual Symptom Scale, Modified Moos menstrual Distress questionnaire, self-assessment questionnaire based on the American College of Obstetricians and Gynaecologists diagnostic criteria for dysmenorrhea. The duration of intervention in the selected clinical trials varied from 1 month to nearly 6 months. Pain assessment time too varied widely in the selected trials.
A thorough literature search has yielded that the pioneering study on the efficacy of fish (oil) in treating dysmenorrhoea first appeared in the 1990s when Deutch published studies claiming that higher marine omega-3 fatty acids correlate with milder menstrual pain.[36],[37] They were basically epidemiological studies that were based upon self-administered questionnaires concerning menstrual history, present symptoms, general health, socioeconomic factors, and general dietary habits. Later, several clinical trials have immensely claimed that fish oil or omega-3 supplements can yield a beneficial effect on the symptoms of dysmenorrhoea when compared to placebo.[12],[13],[14],[16],[17],[18],[19],[20],[22],[23],[24],[27],[30],[34] [Table 1] and [Table 2] also display a general comparison of the efficacy of fish oil with that of other supplementation and/or other interventions. For example, Zafari et al. claimed that the efficacy of fish oil is better than Ibuprofen in the treatment of severe menstrual pain.[32] This contradicts the findings of the other two studies which claimed that Ibuprofen has more effectiveness in reducing mean pain intensity and pain duration.[21],[33] On second thought, these studies also suggested substituting NSAIDs with fish oil supplements. Acupressure on Sanyinjiao point also proved to be better than fish oil supplements in alleviating menstrual pain.[21],[33] Nevertheless, the latter does not involve any soreness or bruising, or other side effects which generally occur at acupressure points. Compared to calcium supplementation, fish oil had proved to be far more effective in such cases.[28]
Studies have also confirmed fish oil supplementation functions better when used in combination with either Vitamin E, B1, and B12, Rosa damascena extracts, Mefenamic acid.[18],[19],[20],[23],[24],[27],[30] Earlier studies have immensely reported the latter used in combination with fish oil supplementation have also some sort of analgesic and anti-inflammatory effects. For example, mefenamic acid is a sort of NSAIDs that is employed in the treatment of various kinds of pain treatment.[38] Such findings are equivalently true in the case of Rosa damascena extracts, Vitamin E, Vitamin B1, and Vitamin B12 where they could yield adjunctive or integrative treatment for pain conditions.[39],[40],[41],[42]
Studies have also ventured into demonstrating specific sources of omega-3 as the best medicament for PD. For instance, Deutch et al.[24] asserted seal oil could be an excellent remedy for ameliorating menstrual pain. This is because seal oil is highly enriched with omega-3 fatty acids and is known to decrease the omega-6/omega-3 ratio and increase EPA, DHA, and the ratio of EPA/AA and DHA/AA in the serum which eventually favors menstrual pain relief.[43],[44] In addition, Sampalis et al. found that Neptune Krill Oil™ (NKO™) to be significantly more effective than omega-3 fish oil in lessening PD and the emotional symptoms of premenstrual syndrome.[29] NKO™ is a natural health product extracted from a zooplankton crustacean named Antarctic krill (scientifically known as Euphausia superba). The superior performance of the NKOTM has been speculated due to its unique biomolecular profile with a combination of phospholipids and triglycerides carrying a long-chain of omega-3 polyunsaturated fatty acids (PUFA), mainly EPA and DHA, and diverse potent antioxidants including Vitamins A and E, astaxanthin, and a novel flavonoid. Last but not the least, Moghadamnia et al. and Hajiabadi et al. employed Clupeonella sp. in their study which is a small fish found commonly in the southern part of the Caspian Sea.[12],[16] This fish is processed locally as canned foods or oils and is abundantly rich in omega-3 fatty acids.[45]
Speaking of any adverse effects of consuming fish oil capsules, it is noteworthy to mention that none of the selected studies have evaluated any serious side effects of consuming fish oil. However, few studies had claimed consumption of high quantity of fish oil can bring about minor side effects such as vomiting, diarrhea, glucose acceleration in diabetic patients, reduction in Vitamin A, D, K, E absorption, etc.[21],[33] As such, they had used lesser doses of fish oil in their studies. In addition, difficulty in swallowing fish oil capsules has also been reported.
To sum up, this review yielded pieces of evidence that fish oil can ameliorate PD in women. The relief from pain was found to be significant in almost all the included studies. Studies that employed Ibuprofen as a positive control claimed that fish oil could also act more or less as effectively as Ibuprofen. Studies have also reported that fish oil combined with other supplements could better lessen dysmenorrheal symptoms when compared to monotherapy with fish oils. The doses of fish oil or omega-3 fatty acids varied widely and hence there was no clear difference in efficacy among the dosages. However, Ibuprofen (of 400 mg as used in most of the studies) is not completely effective and has considerable adverse health effects in the long run. Henceforth, fish oil or omega-3 fatty acids could be useful as a therapeutic agent for PD instead of or combined with Ibuprofen or other NSAIDs.
Recently, a systematic review suggested that omega-3 PUFA supplementation moderately improves chronic pain arising due to dysmenorrhoea.[46] The review found that fish oil was also well effective in alleviating pain arising due to rheumatoid arthritis, osteoarthritis, asthenopia, and premenstrual syndrome. Earlier, several reviews provided limited shreds of evidence regarding the effectiveness and/or efficacy of fish oil in alleviating dysmenorrhoea.[47],[48],[49] The significance of the present review is that the findings provide important insights into the role of fish oil supplementation in curing dysmenorrhoeal symptoms to some extent. A very recent meta-analysis has also favored the effectiveness of fish oil and omega-3 fatty acids in reducing dysmenorrhea.[9]
| Conclusion | | |
The results of the present review provide suggestive evidence for the effectiveness of fish oil or omega-3 supplementation in treating dysmenorrhea. Like other studies, the present study is subjected to few limitations. The total number of studies included in the present study, total sample size, and the average methodological quality of the primary studies might not be sufficient to draw a firm conclusion. Regrettably, evidence is less clear regarding optimal dosing and preparation for fish oil or omega-3 supplementation. Nevertheless, it is very customary to observe that most of us opt for self-medication. Women are advised to switch to fish oil supplements as they are bearing less or nil side effects compared to NSAIDs or other interventions.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Ju H, Jones M, Mishra G. The prevalence and risk factors of dysmenorrhea. Epidemiol Rev 2014;36:104-13.  |
| 2. | Dawood MY. Primary dysmenorrhea: Advances in pathogenesis and management. Obstet Gynecol 2006;108:428-41. |
| 3. | Proctor M, Farquhar C. Diagnosis and management of dysmenorrhoea. BMJ 2006;332:1134-8. |
| 4. | Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr 1980;33:2657-61. |
| 5. | Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: The anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 2010;68:280-9. |
| 6. | Bajalan Z, Alimoradi Z, Moafi F. Nutrition as a potential factor of primary dysmenorrhea: A systematic review of observational studies. Gynecol Obstet Invest 2019;84:209-24. |
| 7. | Roman AS, Schreher J, Mackenzie AP, Nathanielsz PW. Omega-3 fatty acids and decidual cell prostaglandin production in response to the inflammatory cytokine IL-1beta. Am J Obstet Gynecol 2006;195:1693-9. |
| 8. | Burri L, Hoem N, Banni S, Berge K. Marine omega-3 phospholipids: Metabolism and biological activities. Int J Mol Sci 2012;13:15401-19. |
| 9. | Novitasari I, Pamungkasari EP, Prasetya H. The effectiveness of fish oil and ginger drink in reducing dysmenorrhea: A meta analysis. J Matern Child Health 2021;06:353-64. |
| 10. | Coco AS. Primary dysmenorrhea. Am Fam Physician 1999;60:489-96. |
| 11. | Treybig M. Primary dysmenorrhea or endometriosis? Nurse Pract 1989;14:8, 10, 15-8. |
| 12. | Hajiabadi M, Mirhosseini N, Hedayatifar F, Abedinzadeh M, Omranirad A, Moghadamnia AA. The effect of Clupeonella fish oil on dysmenorrhea. Iran Congress Physiol Pharmacol 2007; Volume 18. Seminar Poster. |
| 13. | Harel Z. A contemporary approach to dysmenorrhea in adolescents. Paediatr Drugs 2002;4:797-805. |
| 14. | Harel Z, Biro FM, Kottenhahn RK, Rosenthal SL. Supplementation with omega-3 polyunsaturated fatty acids in the management of dysmenorrhea in adolescents. Am J Obstet Gynecol 1996;174:1335-8. |
| 15. | Kooshki A, Tofighiyan T, Rakhshani MH. Comparison of the effects of marine omega-3 fatty acids and ibuprofen on primary dysmenorrehea. Life Sci J 2013;10:1-3. |
| 16. | Moghadamnia AA, Mirhosseini N, Abadi MH, Omranirad A, Omidvar S. Effect of Clupeonella grimmi (anchovy/kilka) fish oil on dysmenorrhoea. East Mediterr Health J 2010;16:408-13. |
| 17. | Rahbar N, Asgharzadeh N, Ghorbani R. Effect of omega-3 fatty acids on intensity of primary dysmenorrhea. Int J Gynaecol Obstet 2012;117:45-7. |
| 18. | Yaghmaei M, Moradi A, Hosseini R. A comparison of therapeutic effect between mefenamic acid and mefenamic acid plus fish oil in reduction of the severity of pain in primary dysmenorrhea. J Guilan Univ Med Sci 2004;13:68-72. |
| 19. | Agakhani N, Sadagyani M, Jasemi M, Feizi A, Eghtedar S, Mesgarzadeh M, Ebrahimi M. The health effects of fish oil capsules and vitamin B1 tablets on duration and severity of dysmenorrhea. J Urmia Nurs Midwifery Fac 2012;10:494-501. |
| 20. | Aghakhani N, Sadaghiani MM, Rahbar N, Feizi A, Mesgarzadeh M, Ebrahimi M, et al. Effects of fish oil and vitamin B1 on duration and severity of dysmenorrhea in students of high schools, Urmia, Iran. Eur J Pain Suppl 2011;5:69. |
| 21. | Behmanesh F, Zafari M, Zeinalzadeh M, Aghamohammadi A, Akbarpoor S. Comparing the effectiveness of acupressure and fish oil capsules and Ibuprofen on pain severity of primary dysmenorrhea. Indian J Sci Technol 2012;5:3059-64. |
| 22. | Davaneghi S, Tarighat-Esfanjani A, Safaiyan A, Fardiazar Z. The effects of n-3 fatty acids and Rosa damascena extract on primary dysmenorrhea Progr Nutr 2017; 19: 34-40. |
| 23. | Davaneghi S, Tarighat-Esfanjani A, Safaiyan A, Fardiazar Z. Effective reduction of primary dysmenorrheal symptoms through concurrent use of n-fatty acids and Rosa damascena extract (RDE). Prev Care Nurs Midwifery J 2017;7:33-40. |
| 24. | Deutch B, Jørgensen EB, Hansen J. Menstrual discomfort in Danish women reduced by dietary supplements of omega-3 PUFA and B12 (fish oil or seal oil capsules). Nutr Res 2000;20:621-31. |
| 25. | Dolatian M, Jaafari H, Valaei N, Afrakhteh M, Taleban FA, Gachkar L. Study of the effects of fish oil capsules on primary dysmenorrheal. J Zanjan Univ Med Sci 2004;12:7-13. |
| 26. | Demirturk F, Gungor T, Demirturk F, Akbayrak T, Aker EM. Relief of primary dysmenorrhea by supplementation with omega-3 fatty acids. Pain Clinic 2002;14:81-4. |
| 27. | Hosseinlou A, Alinejad V, Alinejad M, Aghakhani N. The effects of fish oil capsules and vitamin B1 tablets on duration and severity of dysmenorrhea in students of high school in Urmia-Iran. Glob J Health Sci 2014;6:124-9. |
| 28. | Mehrpooya M, Eshraghi A, Rabiee S, Larki-Harchegani A, Ataei S. Comparison of the effect of fish-oil and calcium supplementation on treatment of primary dysmenorrhea. Rev Recent Clin Trials 2017;12:148-53. |
| 29. | Sampalis F, Bunea R, Pelland MF, Kowalski O, Duguet N, Dupuis S. Evaluation of the effects of Neptune krill oil on the management of premenstrual syndrome and dysmenorrhea. Altern Med Rev 2003;8:171-9. |
| 30. | Sadeghi N, Paknezhad F, Rashidi Nooshabadi M, Kavianpour M, Jafari Rad S, Khadem Haghighian H. Vitamin E and fish oil, separately or in combination, on treatment of primary dysmenorrhea: A double-blind, randomized clinical trial. Gynecol Endocrinol 2018;34:804-8. |
| 31. | Shaji JCH. A Study on Dysmenorrhea among Adolescent Girls of Selected Schools in Chennai. Tamil Nadu Dr. M.G.R. Medical University; 2011. |
| 32. | Zafari M, Behmanesh F, Agha Mohammadi A. Comparison of the effect of fish oil and ibuprofen on treatment of severe pain in primary dysmenorrhea. Caspian J Intern Med 2011;2:279-82. |
| 33. | Zafari M, Tofighi M, Aghamohammady A, Behmanesh F, Rakhshaee Z. Comparison of the effect of acupressure, fish oil capsules and ibuprofen on treatment of primary dysmenorrhea. Afr J Pharm Pharmacol 2011;5:1115-9. |
| 34. | Zamani M, Arab M, Nasrollahi SH, Mani Kashani KH. The evaluation of fish oil (Omega-3 fatty acids) efficacy in treatment of primary dysmenorrhea in high school female students in Hamadan. J Gorgan Univ Med Sci 2005;7:39-42. |
| 35. | Kharaghani R, Damghanian M. The prevalence of dysmenorrhea in Iran: A systematic review and meta-analysis. Iran Red Crescent Med J 2017;19:E40856. |
| 36. | Deutch B. Menstrual pain in Danish women correlated with low n-3 polyunsaturated fatty acid intake. Eur J Clin Nutr 1995;49:508-16. |
| 37. | Deutch B. Painful menstruation and low intake of n-3 fatty acids. Ugeskr Laeger 1996;158:4195-8. |
| 38. | Cimolai N. The potential and promise of mefenamic acid. Expert Rev Clin Pharmacol 2013;6:289-305. |
| 39. | Hajhashemi V, Ghannadi A, Hajiloo M. Analgesic and anti-inflammatory effects of Rosa damascena hydroalcoholic extract and its essential oil in animal models. Iran J Pharm Res 2010;9:163-8. |
| 40. | Chin KY, Ima-Nirwana S. The role of vitamin E in preventing and treating osteoarthritis – A review of the current evidence. Front Pharmacol 2018;9:946. |
| 41. | Zaringhalam J, Akbari A, Zali A, Manaheji H, Nazemian V, Shadnoush M, et al. Long-term treatment by vitamin B 1 and reduction of serum proinflammatory cytokines, hyperalgesia, and paw edema in adjuvant-induced arthritis. Basic Clin Neurosci 2016;7:331-40. |
| 42. | Buesing S, Costa M, Schilling JM, Moeller-Bertram T. Vitamin B12 as a treatment for pain. Pain Physician 2019;22:E45-52. |
| 43. | Mann NJ, O'Connell SL, Baldwin KM, Singh I, Meyer BJ. Effects of seal oil and tuna-fish oil on platelet parameters and plasma lipid levels in healthy subjects. Lipids 2010;45:669-81. |
| 44. | Conquer JA, Cheryk LA, Chan E, Gentry PA, Holub BJ. Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects. Thromb Res 1999;96:239-50. |
| 45. | Jafroodi H, Khatami M. Gas chromatography identification of fatty acids in Caspian sea anchovy fish oil. North Shilat 1995;9:36-44. |
| 46. | Prego-Dominguez J, Hadrya F, Takkouche B. Polyunsaturated fatty acids and chronic pain: A systematic review and meta-analysis. Pain Physician 2016;19:521-35. |
| 47. | Proctor ML, Murphy PA. Herbal and dietary therapies for primary and secondary dysmenorrhoea. Cochrane Database Syst Rev 2001;3:CD002124. |
| 48. | Latthe PM, Champaneria R, Khan KS. Dysmenorrhoea. BMJ Clin Evid 2011;2011:0813. |
| 49. | Pattanittum P, Kunyanone N, Brown J, Sangkomkamhang US, Barnes J, Seyfoddin V, et al. Dietary supplements for dysmenorrhoea. Cochrane Database Syst Rev 2016;3:CD002124. |
[Figure 1]
[Table 1], [Table 2]
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