Review ArticleOpen Access

Nutritional Protocol for Endometriosis

Emmett J Hughes, D.C., M.S.*

Department of Basic and Clinical Sciences, University of Bridgeport, Connecticut, USA

*Corresponding Author: 
Emmett J Hughes, D.C., M.S.
  Department of Basic and Clinical Sciences
  University of Bridgeport
  Connecticut, USA
  E-mail: ehughes@bridgeport.edu

Received: May 23, 2017; Published: September 28, 2017

Citation: Emmett JH (2017) Nutritional Protocol for Endometriosis. J Nutr Diet Suppl 1(1): 104

Abstract

Endometriosis is a debilitating disease affecting approximately one out of every ten women. Not only does it cause pain during menstruation and intercourse, but it can infertility problems. The current medical treatment involves surgery to remove the endometrial tissue found outside of the uterus along with medications. There are several factors that have been identified as contributing factors. Use of natural alternative to conventional medical treatments can be helpful in mitigation the environmental and dietary factors that contribute to the severity of the disease.

Keywords: Endometriosis; Endometrioma; Xenoestrogens; CA 125

Endometriosis is characterized by dysmenorrhea (painful menses), dyspareunia (painful intercourse), and infertility. Additional finding can include fixed pelvic structures, a uterus that is tipped backwards and rigid, adhesions in the pelvic cavity, tenderness to palpation of the pelvic area, and/or enlarged ovaries. Endometriomas are detected via imaging, as well as laproscopic visualization of endometrial tissue implanted outside of the uterus in the pelvis or abdomen.

It is estimated that 10-15% of menstruating women suffer from endometriosis. The main risk factor is having a mother or sister that also has endometriosis. Additional risk factors include imbalance in estrogens levels, lack of exercise, high fat diet, the use of intrauterine devices. However, the use of Levonorgestrel-releasing intrauterine devices to treat dysmenorrhea and endometriosis with some success [1,2].

There are some emerging theories that increased antigenicity to sperm within the pelvic cavity can also be a risk factor.

There are many environmental factors as well. These include pesticide and herbicide exposure, PCBs, plastics, dioxin, radiation and environmental estrogen (xenoestrogen) exposure, and poor detoxification pathways in the liver. Increased levels of tumor necrosis factor-alpha have been implicated in the development and maintenance of endometriosis [3].

The implantation of endometrial tissue in odd places, such as the brain, lungs, gut and aorta, suggest that the tissue is transported via the lymphatic and blood circulatory systems. Some researchers have proposed that the endometrial tissue is of embryonic origin [4].

Exposure to environmental disruptors of estrogen, such as radiation and dioxin are associated with a higher frequency of endometriosis. Belgium has the highest rates of both dioxin pollution and endometriosis in the world [5,6]. The link between dioxin exposure and endometriosis has been explored in several studies with inconclusive results [7-9].

Estrogen disruptors in the environment include PCBs, pesticides, herbicides, detergents, plastics, and household cleaning products. Significant alterations in sexual development in multiple animal models have been observed. The development of endometriosis as well as other endocrine problems due to exposure to these environmental chemicals in humans has been established as well [10-12].

Immunological alterations have been linked to endometriosis. Increased levels of IL-25, glycodelin-A, IL-6, and IL-8 and well as lower levels of leptin, as well as elevated levels on cytotoxic T cells are just a few of the alterations in the immune system seen in endometriois [13-15].

There have been several genetic mutations that have been demonstrated to have a positive correlation with endometriosis. Additional hereditary factors include abnormalities in detoxification pathways, and genetic mutations affecting the immune system [16-20].

Diagnosis

Most cases of endometriosis occur not with the onset of menses, but begin later and progressively get worse over several years. The triad of symptoms listed above can also include vomiting, diarrhea, pain with urination and defecation, blood in the stool, bladder or nose, and generalized fatigue. Usually the pain begins as acute pain in the pelvis/abdomen starting a few days before the onset of menses and continuing for a few days, or lasting throughout the month. The pain can be so severe that the patient experiences syncope. The extent of endometrial lesions and intensity of the disease does not always correlate. It seems that the lesions that extend deepest are the ones those that cause the most severe symptoms [21]. Diagnosis of deep infiltrating lesions can be corroborated by elevated CA 125 plasma levels [22]. However, this is a marker for malignancy and uterine fibroids as well.

Enlarged areas of ectopic endometrial tissue (endometriomas) on the ovaries are found in two-thirds of patients with endometriosis. Endometriosis may result in miscarriage and/or infertility. This is thought to be due to excess free radical production due to the disease as well as scarring of the fallopian tubes, unruptured follicles, and adhesions. Transvaginal ultrasound can be useful in determining location, size and consistency of endometriomas. However, the only definite diagnosis is via biopsy via laparoscopy or laparotomy.

Diet

There are several aspects of diet that are implicated in the development and severity of endometriosis. More than likely, there is a combination of factors that lead to its development. There are several dietary principles that have been shown to be beneficial in alleviating and/or ameliorating the symptoms of endometriosis.

Research suggests that a predominately vegetarian diet is helpful in reducing and/or eliminating the symptoms of endometriosis [23]. Reduction of inflammatory foods and incorporating anti-inflammatory foods and supplements have been shown to be helpful in treating endometriosis [24,25]. A high-fat diet has been shown to worsen the symptoms of endometriosis [26].

Enhancing detoxification mechanisms is important for several reasons. Detoxification of estrogen, decreasing free radical load and elimination of xenoestrogens are critical.

Antioxidants

Antioxidants, including vitamin C, vitamin E and beta carotene have been shown to have significant positive effects on endometriosis [39-41]. Vitamin C and analogs of vitamin A have been shown to inhibit the growth and regress the size of endometrial cysts [42,43]. Supplementing with vitamin E and n-acetyl cysteine reduced pain related to oxidative stress in endometriosis [44]. Pycnogenol, an extract of pine bark, has been demonstrated to inhibit inflammation, specifically COX 1 and 2 [45]. When combined with oral contraceptives, pycnogenol slowly, but steadily decreases pain scores associated with endometriosis [46].

Herbal Medicines

Studies support the use of various botanicals to treat dysmenorrhea associated with endometriosis. Fenugreek seeds have been shown to decrease the severity and systemic symptoms [47]. Valerian root has also been demonstrated to reduce the severity of symptoms, effecting the contraction of the myometrium [48,49]. Vitex agnes castus, known also as chaste tree, is used traditionally to balance hormone levels. Experimentally, extracts have been shown to decrease luetinizing hormone and prolactin levels while balancing estrogen and progesterone levels [50,51]. Leonorus japonicas Houtt, or Chinese motherwort, has been used to treat dysmenorrhea for thousands of years in China. Over 140 chemicals have been isolated, most of them flavones, alkaloids and diterpenes [52]. These chemicals have been shown to have a positive effect on the uterus, relaxing the myometrium and relieving cramps. Additionally, these chemicals have cardioprotective effects, antioxidant and anti-cancer properties. Taraxacum officinale, known commonly as dandelion root, works principally on the liver and gall bladder, promoting detoxification pathways [53-55]. Studies have demonstrated anti-cancer activity as well [56,57]. The use of Jiawei-Foshou-San formula, a traditional Chinese formula that combines Chinese Angelica, Szechwan Lovage Rhizome and Rhizoma, has been shown to prevent growth of endometrial tissue and help shrink existing ectopic endometrial tissue in animal models [58]. Other studies support the use of traditional Chinese medicine without exploring the specific mechanism [59,60].

Essential Fatty Acids

Both alpha-linolenic acid and gamma-linoleic acid are known to decrease inflammation in general by affecting the type of eicosanoids produced, especially prostaglandins and leukotrienes. Oils derived from flax seeds, soy, rapeseed, walnuts and pumpkin are high in alpha-linolenic acid, whereas borage, black currant and evening primrose oils are high in linoleic acid. Animal fats, which are high in arachidonic acid, lead to an increase in inflammation and increased spasmodic activity in endometriosis due to different prostaglandins produced. Intake of linoleic and alpha-linolenic acids are known to positively influence prostaglandin and leukotrienes synthesis. This has been shown to be an effective strategy in treating dysmenorrhea associated with endometriosis [61-63].

Thiamine (B1)

B1 taken as doses of 100 mg/day has been shown to reduce the symptoms of endometriosis [24,49,64]. There is no known toxicity for thiamine at this dosage.

Magnesium

Magnesium is a known muscle relaxer. It is used to treat constipation, asthma and hypertension due to its ability to relax smooth muscle. It has also been shown to be effective in treating dysmenorrhea and other symptoms of endometriosis [64,65]. Dosing magnesium is based on the individual’s gut physiology. Doses in the range of 400-800 mg/day are usually sufficient, but should be increased to bowel tolerance in severe cases.

Summary of Supplements

Vitamin E: 400- 800 IU/day (start with the lower dose and then add 400 more after two weeks)
Beta-carotene: 50,000 to 150,000 IU/day (caution with pregnancy- avoid doses over 25,000 IU/day)
Vitamin C: 6000 to 10,000 mg/day in divided doses. Higher doses can cause diarrhea.
Flax seed oil: 3000 mg 3x/day
B1 (Thiamine): 100 mg/day
Pycnogenol: 60-150 mg/day
Tinctures of dandelion root, motherwort, and chaste tree (equal parts- 20 drops each) 3x/day
Magnesium: 400-800 mg/day (or to bowel tolerance)

References
  1. 1. Imai A, Matsunami K, Takagi H, Ichigo S (2014) Levonorgestrel-releasing intrauterine device used for dysmenorrhea: five-year literature review. Clin Exp Obstet Gynecol 41: 495-8.
  2. 2. Yoost J, LaJoie AS, Hertweck P, Loveless M (2013) Use of the levonorgestrel intrauterine system in adolescents with endometriosis. J Pediatr Adolesc Gynecol 26: 120-4.
  3. 3. Bullimore DW (2003) Endometriosis is sustained by tumour necrosis factor-alpha. Med Hypotheses 60: 84-8.
  4. 4. Jerman LF, Hey-Cunningham AJ (2015) The role of the lymphatic system in endometriosis: a comprehensive review of the literature. Biol Reprod 92:64.
  5. 5. Sofo V, Götte M, Laganà AS, Salmeri FM, Triolo O, et al. (2015) Correlation between dioxin and endometriosis: an epigenetic route to unravel the pathogenesis of the disease. Arch Gynecol Obstet 292: 973-86.
  6. 6. Martínez-Zamora MA, Mattioli L, Parera J, Abad E, Coloma JL, et al. (2015) Increased levels of dioxin-like substances in adipose tissue in patients with deep infiltrating endometriosis. Hum Reprod 30: 1059-68.
  7. 7. Koninckx PR, Braet P, Kennedy SH, Barlow DH (1994) Dioxin pollution and endometriosis in Belgium. Hum Reprod 9: 1001-2.
  8. 8. Porpora MG, Ingelido AM, di Domenico A, Ferro A, Crobu M, et al. (2006) Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere 63: 1361-7.
  9. 9. Tsukino H, Hanaoka T, Sasaki H, Motoyama H, Hiroshima M, et al. (2005) Associations between serum levels of selected organochlorine compounds and endometriosis in infertile Japanese women. Environ Res 99: 118-25.
  10. 10. Cobellis L, Colacurci N, Trabucco E, Carpentiero C, Grumetto L (2009) Measurement of bisphenol A and bisphenol B levels in human blood sera from healthy and endometriotic women. Biomed Chromatogr 23: 1186-90.
  11. 11. Caserta D, Di Segni N, Mallozzi M, Giovanale V, Mantovani A, et al. (2014) Bisphenol A and the female reproductive tract: an overview of recent laboratory evidence and epidemiological studies. Reprod Biol Endocrinol 12: 37.
  12. 12. McLachlan JA, Simpson E, Martin M (2006) Endocrine disrupters and female reproductive health. Best Pract Res Clin Endocrinol Metab 20: 63-75.
  13. 13. Bungum HF, Nygaard U, Vestergaard C, Martensen PM, Knudsen UB (2016) Increased IL-25 levels in the peritoneal fluid of patients with endometriosis. J Reprod Immunol 114: 6-9.
  14. 14. Kocbek V, Vouk K, Bersinger NA, Mueller MD, Lanišnik Rižner T (2015) Panels of cytokines and other secretory proteins as potential biomarkers of ovarian endometriosis. J Mol Diagn 17: 325-34.
  15. 15. Slabe N, Meden-Vrtovec H, Verdenik I, Kosir-Pogacnik R, Ihan A (2013) Cytotoxic T-Cells in Peripheral Blood in Women with Endometriosis. Geburtshilfe Frauenheilkd 73: 1042-8.
  16. 16. Zondervan KT, Rahmioglu N, Morris AP, Nyholt DR, Montgomery GW, et al. (2016) Beyond Endometriosis Genome-Wide Association Study: From Genomics to Phenomics to the Patient. Semin Reprod Med 34: 242-54.
  17. 17. Jones AV, Hockley JR, Hyde C, Gorman D, Sredic-Rhodes A, et al. (2016) Genome-wide association analysis of pain severity in dysmenorrhea identifies association at chromosome 1p13.2, near the nerve growth factor locus. Pain 157: 2571-81.
  18. 18. Henidi B, Kaabachi S, Mbarik M, Zhioua A, Hamzaoui K (2015) Glutathione S-transferase M1 and T1 gene polymorphisms and risk of endometriosis in Tunisian population. Hum Fertil (Camb) 18: 128-33.
  19. 19. Panda R, Suresh PK (2014) Computational identification and analysis of functional polymorphisms involved in the activation and detoxification genes implicated in endometriosis. Gene 542: 89-97.
  20. 20. Parazzini F, Esposito G, Tozzi L, Noli S, Bianchi S (2016) Epidemiology of endometriosis and its comorbidities. Eur J Obstet Gynecol Reprod Biol 209: 3-7.
  21. 21. Koninckx PR, Oosterlynck D, D'Hooghe T, Meuleman C (1994) Deeply infiltrating endometriosis is a disease whereas mild endometriosis could be considered a non-disease. Ann N Y Acad Sci 734: 333-41.
  22. 22. Muyldermans M, Cornillie FJ, Koninckx PR (1995) CA125 and endometriosis. Hum Reprod Update 1: 173-87.
  23. 23. French L (2005) Dysmenorrhea. Am Fam Physician 71: 285-91.
  24. 24. Xu Z, Zhao F, Lin F, Chen J, Huang Y (2012) Lipoxin A4 inhibits the development of endometriosis in mice: the role of anti-inflammation and anti-angiogenesis. Am J Reprod Immunol 67: 491-7.
  25. 25. Ahn SH, Khalaj K, Young SL, Lessey BA, Koti M (2016) Immune-inflammation gene signatures in endometriosis patients. Fertil Steril 106: 1420-31.
  26. 26. Heard ME, Melnyk SB, Simmen FA, Yang Y, Pabona JM (2016) High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status. Endocrinology 157: 2870-82.
  27. 27. Acharya A, Das I, Singh S, Saha T (2010) Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis. Recent Pat Food Nutr Agric 2: 166-77.
  28. 28. Zhang Y, Cao H, Yu Z, Peng HY, Zhang CJ (2013) Curcumin inhibits endometriosis endometrial cells by reducing estradiol production. Iran J Reprod Med 11: 415-22.
  29. 29. Tsuchiya M, Miura T, Hanaoka T, Iwasaki M, Sasaki H (2007) Effect of soy isoflavones on endometriosis: interaction with estrogen receptor 2 gene polymorphism. Epidemiology 18: 402-8.
  30. 30. Dikshit A, Gomes Filho MA, Eilati E, McGee S, Small C (2015) Flaxseed reduces the pro-carcinogenic micro-environment in the ovaries of normal hens by altering the PG and oestrogen pathways in a dose-dependent manner. Br J Nutr 113: 1384-95.
  31. 31. El Hafidi M, Pérez I, Carrillo S, Cardoso G, Zamora J (2006) Effect of sex hormones on non-esterified fatty acids, intra-abdominal fat accumulation, and hypertension induced by sucrose diet in male rats. Clin Exp Hypertens 28: 669-81.
  32. 32. Yudkin J, Eisa O (1988) Dietary sucrose and oestradiol concentration in young men. Ann Nutr Metab 32: 53-5.
  33. 33. Ferrini RL, Barrett-Connor E (1996) Caffeine intake and endogenous sex steroid levels in postmenopausal women. The Rancho Bernardo Study. Am J Epidemiol 144: 642-4.
  34. 34. Grodstein F, Goldman MB, Ryan L, Cramer DW (1993) Relation of female infertility to consumption of caffeinated beverages. Am J Epidemiol 137: 1353-60.
  35. 35. Chiaffarino F, Bravi F, Cipriani S, Parazzini F, Ricci E, et al. (2014) Coffee and caffeine intake and risk of endometriosis: a meta-analysis. Eur J Nutr 53: 1573-9.
  36. 36. McEvoy JD (2016) Emerging food safety issues: An EU perspective. Drug Test Anal 8: 511-20.
  37. 37. Rocha DA, Torres JP, Reichel K, Novotny EH, Estrella LF, et al. (2016) Determination of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in Brazilian cow milk. Sci Total Environ 572: 177-184.
  38. 38. San Martin BV, Pizarro-Aránguiz N, García-Mendoza D, Araya-Jordan C, Maddaleno A, et al. (2016) A four-year survey in the farming region of Chile, occurrence and human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans, and dioxin -like polychlorinated biphenyls in different raw meats. Sci Total Environ 573: 1278-86.
  39. 39. Erten OU, Ensari TA, Dilbaz B, Cakiroglu H, Altinbas SK, et al. (2013) Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis. J Endometr 5: 17-26.
  40. 40. Darling AM, Chavarro JE, Malspeis S, Harris HR, Missmer SA (2013) A prospective cohort study of Vitamins B, C, E, and multivitamin intake and endometriosis. J Endometr 5: 17-26.
  41. 41. Santanam N, Kavtaradze N, Murphy A, Dominguez C, Parthasarathy S (2013) Antioxidant supplementation reduces endometriosis-related pelvic pain in humans. Transl Res 161: 189-95.
  42. 42. Durak Y, Kokcu A, Kefeli M, Bildircin D, Çelik H, et al. (2013) Effect of vitamin C on the growth of experimentally induced endometriotic cysts. J Obstet Gynaecol Res 39: 1253-8.
  43. 43. Pavone ME, Malpani SS, Dyson M, Kim JJ, Bulun SE (2016) Fenretinide: A Potential Treatment for Endometriosis. Reprod Sci 23: 1139-47.
  44. 44. Ray K, Fahrmann J, Mitchell B, Paul D, King H, et al. (2015) Oxidation-sensitive nociception involved in endometriosis-associated pain. Pain 156: 528-39.
  45. 45. Kohama T, Herai K, Inoue M (2007) Effect of French maritime pine bark extract on endometriosis as compared with leuprorelin acetate. J Reprod Med 52: 703-8.
  46. 46. Maia H Jr, Haddad C, Casoy J (2013) Combining oral contraceptives with a natural nuclear factor-kappa B inhibitor for the treatment of endometriosis-related pain. Int J Womens Health 6: 35-9.
  47. 47. Younesy S, Amiraliakbari S, Esmaeili S, Alavimajd H, Nouraei S (2014) Effects of fenugreek seed on the severity and systemic symptoms of dysmenorrhea. J Reprod Infertil 15: 41-8.
  48. 48. Mirabi P, Dolatian M, Mojab F, Majd HA (2011) Effects of valerian on the severity and systemic manifestations of dysmenorrhea. Int J Gynaecol Obstet 115: 285-8.
  49. 49. Occhiuto F, Pino A, Palumbo DR, Samperi S, De Pasquale R, et al. (2009) Relaxing effects of Valeriana officinalis extracts on isolated human non-pregnant uterine muscle. J Pharm Pharmacol 61: 251-6.
  50. 50. Aksoy AN, Gözükara I, Kabil Kucur S (2014) Evaluation of the efficacy of Fructus agni casti in women with severe primary dysmenorrhea: a prospective comparative Doppler study. J Obstet Gynaecol Res 40: 779-84.
  51. 51. Ibrahim NA, Shalaby AS, Farag RS, Elbaroty GS, Nofal SM, et al. (2008) Gynecological efficacy and chemical investigation of Vitex agnus-castus L. fruits growing in Egypt. Nat Prod Res 22: 537-46.
  52. 52. Shang X, Pan H, Wang X, He H, Li M (2014) Leonurus japonicas Houtt: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. J Ethnopharmacol 152: 14-32.
  53. 53. Bhatia H, Pal Sharma Y, Manhas RK, Kumar K (2015) Traditional phytoremedies for the treatment of menstrual disorders in the district Udhampur, J and K, India. J Ethnopharmacol 160: 202-10.
  54. 54. Nazari A, Fanaei H, Dehpour AR, Hassanzadeh G, Jafari M, et al. (2015) Chemical composition and hepatoprotective activity of ethanolic root extract of Taraxacum Syriacum Boiss against acetaminophen intoxication in rats. Bratisl Lek Listy 116: 41-6.
  55. 55. Mahesh A, Jeyachandran R, Cindrella L, Thangadurai D, Veerapur VP, et al. (2010) Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice. Acta Biol Hung 61: 175-90.
  56. 56. Ovadje P, Chatterjee S, Griffin C, Tran C, Hamm C, et al. (2011) Selective induction of apoptosis through activation of caspase-8 in human leukemia cells (Jurkat) by dandelion root extract. J Ethnopharmacol 133: 86-91.
  57. 57. Ovadje P, Chochkeh M, Akbari-Asl P, Hamm C, Pandey S (2012) Selective induction of apoptosis and autophagy through treatment with dandelion root extract in human pancreatic cancer cells. Pancreas 41: 1039-47.
  58. 58. Tang Q, Shang F, Wang X, Yang Y, Chen G, et al. (2014) Combination use of ferulic acid, ligustrazine and tetrahydropalmatine inhibits the growth of ectopic endometrial tissue: a multi-target therapy for endometriosis rats. J Ethnopharmacol 151: 1218-25.
  59. 59. Fang RC, Tsai YT, Lai JN, Yeh CH, Wu CT (2012) The traditional chinese medicine prescription pattern of endometriosis patients in taiwan: a population-based study. Evid Based Complement Alternat Med 591391.
  60. 60. Su SY, Muo CH, Sung FC, Morisky DE (2014) Reduction of surgery rate in endometriosis patients who take Chinese medicine: a population-based retrospective cohort study. Complement Ther Med 22: 632-9.
  61. 61. Wu CC, Huang MY, Kapoor R, Chen CH, Huang YS (2008) Metabolism of omega-6 polyunsaturated fatty acids in women with dysmenorrhea. Asia Pac J Clin Nutr 1: 216-9.
  62. 62. Harel Z, Lilly C, Riggs S, Vaz R, Drazen J (2000) Urinary leukotriene (LT) E(4) in adolescents with dysmenorrhea: a pilot study. J Adolesc Health 27: 151-4.
  63. 63. Abu JI, Konje JC (2000) Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis. Hum Reprod Update 6: 200-5.
  64. 64. Proctor ML, Murphy PA (2001) Herbal and dietary therapies for primary and secondary dysmenorrhoea. Cochrane Database Syst Re CD002124.
  65. 65. Mesrine S, Clavel-Chapelon F, Boutron-Ruault MC (2013) Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol 177: 420-30.
  66. 66. Fugh-Berman A, Kronenberg F (2003) Complementary and alternative medicine (CAM) in reproductive-age women: a review of randomized controlled trials. Reprod Toxicol 17: 137-52.

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