Abstract
Background: Hypothyroidism is a common endocrine disease in the world that causes morbidity and mortality due to its association with metabolic diseases, especially in old age, and longterm treatment with levothyroxine causes many side effects for patients. Treatment with herbal medicine can regulate thyroid hormones and prevent side effects.
Objective: The purpose of this systematic review is the evaluation of the effect of herbal medicine on the signs and symptoms of primary hypothyroidism.
Methods: PubMed, Embase, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials were searched until 4 May, 2021. We selected randomized clinical trials (RCTs) that have assessed the effect of herbal medicine on hypothyroidism.
Results: Out of 771 articles, 4 trials with 186 participants were included. In one study, Nigella sativa L. caused a significant decrease in weight (P=0.004) and body mass index (BMI) (P=0.002). TSH levels were reported to be decreased and T3 increased in the treatment group (P =0.03) (P=0.008), respectively. In another study on Nigella sativa L., results did not show a significant difference between the two groups (p=0.02). A significant decrease in total cholesterol (CHL) and fasting blood sugar (FBS) was reported in participants with negative anti-thyroid peroxidase (anti-TPO) antibodies. In patients with positive anti-TPO antibodies, a significant increase in total cholesterol and FBS was observed in the intervention group (p=0.02). In the third RCT, T3 in the ashwagandha group at 4 and 8 weeks significantly increased by 18.6% (p=0.012) and 41.5% (p < 0.001), respectively. A noticeable increase was found in the T4 level from baseline by 9.3% (p= 0.002) and 19.6% (p < 0.001) at 4 and 8 weeks, respectively. TSH levels fell remarkably in the intervention group compared to placebo at 4 weeks (p <0.001) and 8 weeks (p <0.001), respectively. In the last article selected, Mentha x Piperita L. showed no significant difference in fatigue scores between intervention and control groups at the midpoint (day 7), while fatigue scores improved in the intervention group in all subscales compared to the control group on day 14.
Conclusion: Some herbal remedies, including Nigella sativa L., ashwagandha, and Mentha x Piperita L., can improve the signs and symptoms of primary hypothyroidism, but using a more extensive and advanced methodology will provide us with more complete results.
Graphical Abstract
[1]
Delshad H, Mehran L, Tohidi M, Assadi M, Azizi F. The incidence of thyroid function abnormalities and natural course of subclinical thyroid disorders, Tehran, I.R. Iran. J Endocrinol Invest 2012; 35(5): 516-21.
[PMID: 21971483]
[PMID: 21971483]
[2]
Mehran L, Amouzegar A, Rahimabad P, Tohidi M, Tahmasebinejad Z, Azizi F. Thyroid function and metabolic syndrome: A population-based thyroid study. Horm Metab Res 2017; 49(3): 192-200.
[http://dx.doi.org/10.1055/s-0042-117279] [PMID: 28351085]
[http://dx.doi.org/10.1055/s-0042-117279] [PMID: 28351085]
[3]
Ke LQ, Hu Y, Yang K, Tong N. Chinese herbal medicines for hypothyroidism. Cochrane Database Syst Rev 2015; 12(2): CD008779.
[PMID: 25914906]
[PMID: 25914906]
[4]
Dunn D, Turner C. Hypothyroidism in Women. Nurs Womens Health 2016; 20(1): 93-8.
[http://dx.doi.org/10.1016/j.nwh.2015.12.002] [PMID: 26902444]
[http://dx.doi.org/10.1016/j.nwh.2015.12.002] [PMID: 26902444]
[5]
Najafi L, Malek M, Hadian A, Ebrahim Valojerdi A, Khamseh ME, Aghili R. Depressive symptoms in patients with subclinical hypothyroidism – the effect of treatment with levothyroxine: A double-blind randomized clinical trial. Endocr Res 2015; 40(3): 121-6.
[http://dx.doi.org/10.3109/07435800.2014.896924] [PMID: 25775223]
[http://dx.doi.org/10.3109/07435800.2014.896924] [PMID: 25775223]
[6]
Taylor PN, Albrecht D, Scholz A, et al. Global epidemiology of hyperthyroidism and hypothyroidism. Nat Rev Endocrinol 2018; 14(5): 301-16.
[http://dx.doi.org/10.1038/nrendo.2018.18] [PMID: 29569622]
[http://dx.doi.org/10.1038/nrendo.2018.18] [PMID: 29569622]
[7]
Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. Williams Textbook of Endocrinology E-Book. Elsevier Health Sciences 2015.
[8]
Hennessey JV. Historical and current perspective in the use of thyroid extracts for the treatment of hypothyroidism. Endocr Pract 2015; 21(10): 1161-70.
[http://dx.doi.org/10.4158/EP14477.RA] [PMID: 26121440]
[http://dx.doi.org/10.4158/EP14477.RA] [PMID: 26121440]
[9]
Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: Prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014; 24(12): 1670-751.
[http://dx.doi.org/10.1089/thy.2014.0028] [PMID: 25266247]
[http://dx.doi.org/10.1089/thy.2014.0028] [PMID: 25266247]
[10]
Roberts LM, Pattison H, Roalfe A, et al. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med 2006; 145(8): 573-81.
[http://dx.doi.org/10.7326/0003-4819-145-8-200610170-00006] [PMID: 17043339]
[http://dx.doi.org/10.7326/0003-4819-145-8-200610170-00006] [PMID: 17043339]
[11]
Mahjoub F, Salari R, Yousefi M, Mohebbi M, Saki A, Akhavan Rezayat K. Effect of Pistacia atlantica kurdica gum on diabetic gastroparesis symptoms: A randomized, triple-blind placebo-controlled clinical trial. Electron Physician 2018; 10(7): 6997-7007.
[http://dx.doi.org/10.19082/6997] [PMID: 30128090]
[http://dx.doi.org/10.19082/6997] [PMID: 30128090]
[12]
Yousefi M, Hoseini SM, Salari R. Evaluating the clinical efficacy of Guggulu resin on constipation: A randomised clinical trial. Adv Integr Med 2016; 3(3): 98-102.
[http://dx.doi.org/10.1016/j.aimed.2016.11.004]
[http://dx.doi.org/10.1016/j.aimed.2016.11.004]
[13]
Xiao H, Tan C, Yang G, Dou D. The effect of red ginseng and ginseng leaves on the substance and energy metabolism in hypothyroidism rats. J Ginseng Res 2017; 41(4): 556-65.
[http://dx.doi.org/10.1016/j.jgr.2016.11.005] [PMID: 29021704]
[http://dx.doi.org/10.1016/j.jgr.2016.11.005] [PMID: 29021704]
[14]
Erfani Majd N, Shahriari A. Effect of aloe vera on histomorphometric structure of thyroid gland, T3 and T4 levels in diabetic rats. J Mazandaran Univ Med Sci 2016; 25(133): 255-66.
[15]
Dharmananda S. Treatments for thyroid diseases with Chinese herbal medicine portland: ITM;. 1996; 10.
[16]
Kar A, Panda S, Bharti S. Relative efficacy of three medicinal plant extracts in the alteration of thyroid hormone concentrations in male mice. J Ethnopharmacol 2002; 81(2): 281-5.
[http://dx.doi.org/10.1016/S0378-8741(02)00048-X] [PMID: 12065164]
[http://dx.doi.org/10.1016/S0378-8741(02)00048-X] [PMID: 12065164]
[17]
Panda S, Kar A. Guggulu (Commiphora mukul) potentially ameliorates hypothyroidism in female mice. Phytother Res 2005; 19(1): 78-80.
[http://dx.doi.org/10.1002/ptr.1602] [PMID: 15798994]
[http://dx.doi.org/10.1002/ptr.1602] [PMID: 15798994]
[18]
Roshangar F, Modaresi M, Toghyani M. Effect of marshmallow’s root extract on thyroid hormones in broilers. Res J Appl Sci Eng Technol 2014; 7(1): 161-4.
[http://dx.doi.org/10.19026/rjaset.7.234]
[http://dx.doi.org/10.19026/rjaset.7.234]
[19]
Ward L. Thyroid and parathyroid diseases: New insights into some old and some new issues intech;. 2012; 226.
[20]
Farhangi MA, Dehghan P, Tajmiri S, Abbasi MM. The effects of Nigella sativa on thyroid function, serum Vascular Endothelial Growth Factor (VEGF) – 1, Nesfatin-1 and anthropometric features in patients with Hashimoto’s thyroiditis: A randomized controlled trial. BMC Complement Altern Med 2016; 16(1): 471.
[http://dx.doi.org/10.1186/s12906-016-1432-2] [PMID: 27852303]
[http://dx.doi.org/10.1186/s12906-016-1432-2] [PMID: 27852303]
[21]
Tekieh M, Esfahanian F, Emadi F, Gholami M, Emaratkar E. Effect of Nigella sativa on thyroid function in patients with hypothyroidism treated with levothyroxine: A triple-blind randomized controlled trial. Med Sci 2019; 23(98): 606-14.
[22]
Sharma AK, Basu I, Singh S. Efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients: A double-blind, randomized placebo-controlled trial. J Altern Complement Med 2018; 24(3): 243-8.
[http://dx.doi.org/10.1089/acm.2017.0183] [PMID: 28829155]
[http://dx.doi.org/10.1089/acm.2017.0183] [PMID: 28829155]
[23]
Hawkins J, Hires CY, Dunne EW, Keenan LA. Aromatherapy reduces fatigue among women with hypothyroidism: A randomized placebo-controlled clinical trial. J Complement Integr Med 2019; 17(1): 229.
[24]
Zaoui A, Cherrah Y, Alaoui K, Mahassine N, Amarouch H, Hassar M. Effects of Nigella sativa fixed oil on blood homeostasis in rat. J Ethnopharmacol 2002; 79(1): 23-6.
[http://dx.doi.org/10.1016/S0378-8741(01)00342-7] [PMID: 11744291]
[http://dx.doi.org/10.1016/S0378-8741(01)00342-7] [PMID: 11744291]
[25]
Datau EA. Wardhana, Surachmanto EE, Pandelaki K, Langi JA, Fias. Efficacy of Nigella sativa on serum free testosterone and metabolic disturbances in central obese male. Acta Med Indones 2010; 42(3): 130-4.
[PMID: 20724766]
[PMID: 20724766]
[26]
Ismail M, Zabid Y, Hanefi O, Ramazan UJIVJ. Effect of Nigella sativa L. on serum concentration of thyroid hormone, thyroid stimulating hormone and glucose in alloxan-induced diabetic rabbits. Ir Vet J 2003; 56(9): 462-4.
[27]
Ghosheh OA, Houdi AA, Crooks PA. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J Pharm Biomed Anal 1999; 19(5): 757-62.
[http://dx.doi.org/10.1016/S0731-7085(98)00300-8] [PMID: 10698539]
[http://dx.doi.org/10.1016/S0731-7085(98)00300-8] [PMID: 10698539]
[28]
Khader M, Eckl PM. Thymoquinone: An emerging natural drug with a wide range of medical applications. Iran J Basic Med Sci 2014; 17(12): 950-7.
[PMID: 25859298]
[PMID: 25859298]
[29]
Houcher Z, Boudiaf K, Benboubetra M, Houcher B. Effects of methanolic extract and commercial oil of Nigella sativa L. on blood glucose and antioxidant capacity in alloxan-induced diabetic rats. Pteridines 2007; 18(1): 8-18.
[http://dx.doi.org/10.1515/pteridines.2007.18.1.8]
[http://dx.doi.org/10.1515/pteridines.2007.18.1.8]
[30]
Panahi M, Namjoyan F, Shakerin Z. Evaluation of antioxidant effects of Nigella sativa extract on the ultra structure of neural tube defects in diabetic rats’s offspring. Jundishapur J Nat Pharm Prod 2011; 6(1): 16-23.
[31]
Goga A, Hasic S, Becirovic S, Cavar S. Phenolic compounds and antioxidant Activity of extracts of Nigella sativa L. Bull Chem Technol Bosnia Herzegovina 2012; 39: 15-9.
[32]
Noor NA, Fahmy HM, Mohammed FF, Elsayed AA, Radwan NM. Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats. Int J Clin Exp Pathol 2015; 8(6): 6269-86.
[PMID: 26261504]
[PMID: 26261504]
[33]
Viglietto G, Maglione D, Rambaldi M, et al. Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PlGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 1995; 11(8): 1569-79.
[PMID: 7478581]
[PMID: 7478581]
[34]
Soh EY, Sobhi SA, Wong MG, et al. Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines. Surgery 1996; 120(6): 944-7.
[http://dx.doi.org/10.1016/S0039-6060(96)80038-9] [PMID: 8957478]
[http://dx.doi.org/10.1016/S0039-6060(96)80038-9] [PMID: 8957478]
[35]
Lieb W, Safa R, Benjamin EJ, et al. Vascular endothelial growth factor, its soluble receptor, and hepatocyte growth factor: Clinical and genetic correlates and association with vascular function. Eur Heart J 2009; 30(9): 1121-7.
[http://dx.doi.org/10.1093/eurheartj/ehp007] [PMID: 19223316]
[http://dx.doi.org/10.1093/eurheartj/ehp007] [PMID: 19223316]
[36]
Khalawi A, Al-Robai AA, Khoja SM, Shaker S. Can Nigella sativa oil (nso) reverse hypothyroid status induced by PTU in rat? biochemical and histological studies. Life Sci J 2013; 10: 802-11.
[37]
Hadjzadeh MAR, Pakdel R, Hadjzadeh H, Sadegh MM, Hosseini M, Emami B. The effects of hydroalcoholic extract of Nigella sativa seeds on serum estradiol and prolactin levels and obstetric criteria due to hypothyroidism in rat. Adv Biomed Res 2017; 6(1): 166.
[http://dx.doi.org/10.4103/2277-9175.221860] [PMID: 29387677]
[http://dx.doi.org/10.4103/2277-9175.221860] [PMID: 29387677]
[38]
Shariatifar A, Riazi M, Ebnolelm M, Jahromy MH. Effects of Nigella sativa L. seed extract on fatigue, blood biochemical parameters and thyroid function in male mice. Chin Med (Irvine Calif) 2014; 5(1): 16-21.
[http://dx.doi.org/10.4236/cm.2014.51003]
[http://dx.doi.org/10.4236/cm.2014.51003]
[39]
Al-Ghamdi MS. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76(1): 45-8.
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[http://dx.doi.org/10.1016/S0378-8741(01)00216-1] [PMID: 11378280]
[40]
Arjumand S, Shahzad M, Shabbir A, Yousaf MZ. Thymoquinone attenuates rheumatoid arthritis by downregulating TLR2, TLR4, TNF-α, IL-1, and NFκB expression levels. Biomed Pharmacother 2019; 111: 958-63.
[http://dx.doi.org/10.1016/j.biopha.2019.01.006] [PMID: 30841475]
[http://dx.doi.org/10.1016/j.biopha.2019.01.006] [PMID: 30841475]
[41]
Bashir MU, Qureshi HJ. Effect of Nigella sativa seeds extract on Serum C-reactive protein in albino rats. Annals of KEMU 2014; 20(1): 35.
[42]
Butt MS, Sultan MT. Nigella sativa: Reduces the risk of various maladies. Crit Rev Food Sci Nutr 2010; 50(7): 654-65.
[http://dx.doi.org/10.1080/10408390902768797] [PMID: 20694927]
[http://dx.doi.org/10.1080/10408390902768797] [PMID: 20694927]
[43]
Hayatdavoudi P, Khajavi Rad A, Rajaei Z, Hadjzadeh MA. Renal injury, nephrolithiasis and Nigella sativa: A mini review. Avicenna J Phytomed 2016; 6(1): 1-8.
[PMID: 27247917]
[PMID: 27247917]
[44]
Islam M, Guha B, Hosen S, Riaz T, Shahadat S, Da Rocha Sousa L. Nigellalogy: A review on Nigella sativa. MOJ 2017; 3(6): 167-81.
[45]
Chandrasekhar K, Kapoor J, Anishetty S. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med 2012; 34(3): 255-62.
[http://dx.doi.org/10.4103/0253-7176.106022] [PMID: 23439798]
[http://dx.doi.org/10.4103/0253-7176.106022] [PMID: 23439798]
[46]
Olff M, Güzelcan Y, de Vries GJ, Assies J, Gersons BPR. HPA- and HPT-axis alterations in chronic posttraumatic stress disorder. Psychoneuroendocrinology 2006; 31(10): 1220-30.
[http://dx.doi.org/10.1016/j.psyneuen.2006.09.003] [PMID: 17081699]
[http://dx.doi.org/10.1016/j.psyneuen.2006.09.003] [PMID: 17081699]
[47]
Dunn AJ. Cytokine activation of the HPA axis. Ann N Y Acad Sci 2000; 917(1): 608-17.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05426.x] [PMID: 11268389]
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb05426.x] [PMID: 11268389]
[48]
Turnbull AV, Rivier C. Regulation of the HPA axis by cytokines. Brain Behav Immun 1995; 9(4): 253-75.
[http://dx.doi.org/10.1006/brbi.1995.1026] [PMID: 8903845]
[http://dx.doi.org/10.1006/brbi.1995.1026] [PMID: 8903845]
[49]
Kour K, Pandey A, Suri KA, Satti NK, Gupta KK, Bani S. Restoration of stress-induced altered T cell function and corresponding cytokines patterns by Withanolide A. Int Immunopharmacol 2009; 9(10): 1137-44.
[http://dx.doi.org/10.1016/j.intimp.2009.05.011] [PMID: 19524704]
[http://dx.doi.org/10.1016/j.intimp.2009.05.011] [PMID: 19524704]
[50]
Singh D, Aggarwal A, Maurya R, Naik S. Withania somnifera inhibits NF-κB and AP-1 transcription factors in human peripheral blood and synovial fluid mononuclear cells. Phytother Res 2007; 21(10): 905-13.
[http://dx.doi.org/10.1002/ptr.2180] [PMID: 17562568]
[http://dx.doi.org/10.1002/ptr.2180] [PMID: 17562568]
[51]
Donkoh A. Ambient temperature: A factor affecting performance and physiological response of broiler chickens. Int J Biometeorol 1989; 33(4): 259-65.
[http://dx.doi.org/10.1007/BF01051087] [PMID: 2613371]
[http://dx.doi.org/10.1007/BF01051087] [PMID: 2613371]
[52]
Bobek S, Niezgoda J, Pietras M, Kacińska M, Ewy Z. The effect of acute cold and warm ambient temperatures on the thyroid hormone concentration in blood plasma, blood supply, and oxygen consumption in Japanese quail. Gen Comp Endocrinol 1980; 40(2): 201-10.
[http://dx.doi.org/10.1016/0016-6480(80)90123-9] [PMID: 7364210]
[http://dx.doi.org/10.1016/0016-6480(80)90123-9] [PMID: 7364210]
[53]
Magdub A, Johnson HD, Belyea RL. Effect of environmental heat and dietary fiber on thyroid physiology of lactating cows. J Dairy Sci 1982; 65(12): 2323-31.
[http://dx.doi.org/10.3168/jds.S0022-0302(82)82504-6] [PMID: 6298292]
[http://dx.doi.org/10.3168/jds.S0022-0302(82)82504-6] [PMID: 6298292]
[54]
Parvinroo S, Naghibi F, Zahediasl S, Kamalinejad M, Sabetkasaei M. The effects of seeds with hot and cold temperaments on serum thyroid hormones, corticosterone and urine vanillylmandelic acid concentrations of healthy rats. J Ethnopharmacol 2014; 156: 216-21.
[http://dx.doi.org/10.1016/j.jep.2014.08.026] [PMID: 25193009]
[http://dx.doi.org/10.1016/j.jep.2014.08.026] [PMID: 25193009]
[55]
Mohammadi Farsani G, Naseri M, Hosseini S, et al. The Evaluation of basic and neurohormonal parameters in hot or cold temperament person proposed in Iranian Traditional Medicine: An observational study. J Contempor Med Sci 2020; 6(4): 176-80.
[http://dx.doi.org/10.22317/jcms.v6i4.709]
[http://dx.doi.org/10.22317/jcms.v6i4.709]
[56]
de Carvalho GA, Paz-Filho G, Mesa Junior C, Graf H. Management of endocrine disease: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults. Eur J Endocrinol 2018; 178(6): R231-44.
[http://dx.doi.org/10.1530/EJE-17-0947] [PMID: 29490937]
[http://dx.doi.org/10.1530/EJE-17-0947] [PMID: 29490937]
[57]
Rossaint J, Berger C, Kraft F, Van Aken H, Giesbrecht N, Zarbock A. Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation. Br J Anaesth 2015; 114(3): 509-19.
[http://dx.doi.org/10.1093/bja/aeu340] [PMID: 25324349]
[http://dx.doi.org/10.1093/bja/aeu340] [PMID: 25324349]
[58]
Goren I, Godny L, Reshef L, et al. Starch consumption may modify antiglycan antibodies and fecal fungal composition in patients with ileo-anal pouch. Inflamm Bowel Dis 2019; 25(4): 742-9.
[http://dx.doi.org/10.1093/ibd/izy370] [PMID: 30535148]
[http://dx.doi.org/10.1093/ibd/izy370] [PMID: 30535148]
[59]
Metro D, Cernaro V, Papa M, Benvenga S. Marked improvement of thyroid function and autoimmunity by Aloe barbadensis miller juice in patients with subclinical hypothyroidism. J Clin Transl Endocrinol 2018; 11: 18-25.
[http://dx.doi.org/10.1016/j.jcte.2018.01.003] [PMID: 29527506]
[http://dx.doi.org/10.1016/j.jcte.2018.01.003] [PMID: 29527506]
[60]
Singh K, Thakar A. A clinical study to evaluate the role of Triphaladya Guggulu along with Punarnavadi Kashaya in the management of hypothyroidism. Ayu 2018; 39(1): 50-5.
[http://dx.doi.org/10.4103/ayu.AYU_62_17] [PMID: 30595635]
[http://dx.doi.org/10.4103/ayu.AYU_62_17] [PMID: 30595635]
[61]
Sathyapalan T, Manuchehri AM, Thatcher NJ, et al. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study. J Clin Endocrinol Metab 2011; 96(5): 1442-9.
[http://dx.doi.org/10.1210/jc.2010-2255] [PMID: 21325465]
[http://dx.doi.org/10.1210/jc.2010-2255] [PMID: 21325465]
