| کلیدواژههای انگلیسی مقاله |
Trigonella, Spice, Drug-related side effects and adverse reactions, Clinical trial, Persian medicine, What&,rsquo s Known Fenugreek (Trigonella foenum-graecum) is a plant that has been widely used both as a culinary spice and a medicinal herb. What&,rsquo s New The most frequently reported adverse effect associated with oral fenugreek ingestion is mild gastrointestinal discomfort. Other documented adverse events include hypoglycemia, suspected hypokalemia, allergic reactions, a maple syrup-like odor in the sweat or urine of mothers and breastfed infants, and interactions with specific medications. IntroductionIn recent years, public interest in complementary and alternative medicine (CAM) has grown significantly. Concurrently, global research publications on the application of CAM in clinical practice have increased. The use of herbal medicines and medicinal plants for common illnesses is becoming more popular, aligning with the rising integration of CAM alongside modern conventional treatments for a wide range of conditions. 1, - 4, This growing attention from both patients and the scientific community is partly due to the incomplete success of conventional medications in treating or managing numerous common ailments, including gynecological disorders, type 2 diabetes mellitus, male reproductive problems, hyperlipidemia, cardiovascular conditions, and COVID-19. 5, - 10, Furthermore, several studies documented a patient perception that the herbal and natural remedies are safer than synthetic pharmaceutical alternatives. 5, - 10, Fenugreek (Trigonella foenum-graecum L.) is an annual plant from the Fabaceae family, native to some regions of Asia, Africa, southern Europe, and also Canada. The plant typically reaches 30-60 cm in height and features trifoliate green leaves. Its flowers produce slender, boat-shaped pods, each containing an average of 10-20 green-brown seeds. 11, Fenugreek seeds and leaves are used variously as a spice, food additive, flavoring, condiment, preservative, and vegetable. 12, For example, the seeds and leaves are utilized in diverse culinary applications, including Iranian stews, Swiss cheese flavoring, German syrup and bitter rum, and Egyptian mixed seed powder for flatbread. They are also used in curries, as dyes, and&,mdash when roasted&,mdash as a coffee substitute in Africa, while young seedlings are consumed as a vegetable. 11, , 13, The pharmacotherapeutic potential of fenugreek is derived from its rich array of bioactive components, including steroids, polyphenols, alkaloids, saponins, hydrocarbons, and galactomannan fiber. Furthermore, the plant contains substantial quantities of furostanolic saponins, such as trigoneoside, isoorientin, vitexin, and isovitexin. The seeds are a source of triglycerides, fatty acids, polysaccharides, notably a high concentration of galactomannan and flavone C-glycosides. 14, - 17, Nutritionally, fenugreek is rich in vitamin A, B1, B2, C, niacin, and nicotinic acid. 18, The seeds contain 28.4% protein, 9.3% fiber, and 7.1% fat, 19, in addition to minerals such as magnesium, iron, copper, chromium, and calcium. 20, Fenugreek seed oil contains omega-6 fatty acids, which are beneficial in managing coronary heart disease, inflammation, and cancer. It also contains palmitic acid, pinene, and other components with antioxidant activity. 21, The oligosaccharides in fenugreek seeds are known to confer health benefits in type 2 diabetes by preventing the rapid absorption of monosaccharides, 17, and fenugreek supplementation has been shown to significantly improve both fasting and postprandial blood glucose levels. 22, Furthermore, diosgenin, a compound found in fenugreek, seems to prevent colon cancer 23, and has beneficial effects in hyperlipidemic patients. 24, Fenugreek extract was also demonstrated to increase serum total testosterone levels in males. 25, A saponin-rich fenugreek extract can generate multi-bioactive extracts that inhibit pancreatic lipase and cholesterol bioaccessibility, potentially leading to a hypocholesterolemic effect. 26, Additionally, fenugreek seed is recognized for its ability to improve breast milk production. 27, Given the increasing popularity of using herbal medicine to treat various diseases and conditions, 5, , 9, , 28, , 29, there is a growing need to evaluate and report the adverse effects of medicinal plants such as fenugreek. Therefore, this scoping review aimed to comprehensively examine human studies on fenugreek consumption, including clinical trials, case reports, and case series, to identify any associated adverse effects. The findings of this study could provide valuable information for a wide audience, particularly for patients who use fenugreek as an herbal remedy. Materials and Methods Study Design This scoping review aimed to collect information on the adverse effects associated with fenugreeks consumption in human studies. A systematic search was conducted using various keywords and related MeSH terms, such as &,ldquo Trigonellas,&,rdquo &,ldquo Trigonella foenum-graecum&,rdquo , &,ldquo Trigonella foenum graecum&,rdquo , &,ldquo Fenugreek&,rdquo , &,ldquo Fenugreeks&,rdquo , &,ldquo Foenumgraecum&,rdquo , &,ldquo Adverse Effects&,rdquo , &,ldquo Clinical Trial&,rdquo , and &,ldquo Case Report&,rdquo and &,ldquo Case Series&,rdquo in multiple databases and search engines, such as Google Scholar, Web of Science, PubMed, Scopus, and Science Direct, from January 1990 to September 2024. The reference lists of retrieved articles were also screened.The study included only English-published articles that documented the adverse effects of fenugreeks on humans. Animal studies, non-English publications, and articles for which the full text was unavailable were excluded. The eligible articles were reviewed, and relevant data were extracted and recorded in Microsoft Excel software (Microsoft Press, Redmond, WA, USA). Finally, the included articles were categorized as clinical trials, case reports, or case series. Data Extraction For clinical trials, the extracted data included, the health status of the participants, the number of subjects in the fenugreek and control groups, the formulation, dosage, and administration schedule of fenugreek, the interval between consumption and follow-up, concomitant interventions, study design, and any reported adverse effects. For case reports and case series, the extracted information included article title, patient demographics (age, sex), health status, medical history, clinical examination findings, as well as the formulation, dosage, administration schedule, and reported adverse effects of fenugreek. Following the review and data extraction, the studies were categorized, and the adverse effects observed in the selected studies were summarized using the available data and tables.The study protocol was approved by the Research Ethics Committee of Shiraz University of Medical Sciences (code, IR.SUMS.MED.REC.1399.420).ResultsBased on the inclusion criteria, the relevant data from the selected articles were organized into tables. The final review included 60 articles, comprising 50 clinical trials and 10 case reports. Clinical Trial Articles Of the 50 clinical trials, 14 reported adverse effects associated with fenugreek consumption, 23 reported no adverse effects, and the remaining 13 did not mention adverse effects.As shown in table 1,, among the 14 clinical trials reporting adverse effects, 57 out of 384 participants in the fenugreek group experienced them. These studies involved healthy individuals, 30, women with low libido, 31, lactating women, 32, overweight patients, 33, and individuals with type 1 and type 2 diabetes. 34, , 35, Authors/ year of publicationCountry Participants Health status Preparation and dosageDuration of treatmentAdverse effects reported from the fenugreek groupAdverse effects reported in the control groupSteel et al., 2011 36, Australia30Healthy menTestophen tablets contain 300 mg of fenugreek powder two times a day6 weeksThree cases of mild stomach pain before mealsWas not observedRao et al., 2015 37, Australia40Women with low libido600 mg of fenugreek seed extract per dayIn two consecutive menstrual periodsTwo cases of exacerbation of migraine, two cases of refluxWas not observedRao et al., 2020 31, Australia50Benign prostatic hyperplasia 600 mg of fenugreek seed extract per day12 weeksThree cases of refluxOne case of refluxNajdi et al., 2019 38, Saudi Arabia5Type 2 diabetes that was treated with metformin2 g of fenugreek in capsule form (one 500 mL capsule after breakfast, two capsules after lunch, and one capsule after dinner)12 weeksOne case of hypoglycemiaWas not observedBumrungpert et al., 2018 32, Thailand25Lactating lady3 capsules (200 mg fenugreek seeds, 120 mg ginger, 100 mg turmeric) 3 times a day4 weeksTwo cases of flatulence, two cases of urine with the odor of maple syrupTwo cases of urine with the odor of maple syrupChevassus et al., 2009 33, France24HealthyFenugreek tablets (one group, 588 mg, and another group, 1176 mg)3-14 days with 14 days in betweenOne case of heartburn, two cases of the specific smell of urineWas not observedChevassus et al., 2010 39, France19OverweightFenugreek tablets contain 1176 mg of hydroalcoholic extract of fenugreek seeds daily6 weeksFour cases of mild gastrointestinal symptoms, one case of a specific odor of urine and sweatWas not observedEmtiazy et al., 2018 40, Iran 28Mild asthmaTen mL of fenugreek seed extract syrup, two times a day4 weeksTwo cases of increased sanitary napkin use during menstruationWas not observedSharma et al., 1990 34, India 10Type 1 diabetes50 g of fenugreek seed powder, two times a day, at lunch and dinner, added to bread10 daysFour cases of gastrointestinal symptoms, including diarrhea and bloatingWas not observedGupta et al., 2001 35, India 12Type 2 diabetes1 g of hydroalcoholic extract of fenugreek seeds in capsule form2 monthsFive people with mild abdominal distensionWas not observedAbdel-Barry et al., 2000 30, Iraq20Healthy40 mg per Kg bodyweight of fenugreek leaf extract in 10 mL of boiled waterA single doseFour cases felt hungry, four cases of frequent urination, and four cases of dizziness.Was not observedLu et al., 2008 41, China 46Type 2 diabetesSix 35% pills from seeds three times a day12 weeksTwo cases of nausea and one case of diarrheaWas not observedSudheeran et al., 2016 42, &,nbsp India20Healthy500 mg capsules, including 300 mg of fiber and 200 mg of turmeric, two times daily before breakfast and at bedtime30 daysTwo cases of decreased appetiteOne case of gastrointestinal problemsMirgoaybayat et al., 43, &,nbsp Iran55Polycystic Ovary SyndromeTake 333 mg of fenugreek capsules three times a day (Mootta capsules contain 333 mg of dry fenugreek extract, standardized to contain 53.7% trigonelline, the key phytochemical compound in fenugreek)2 monthsSix (10.9%) cases of nausea32 (58.2%) cases of nausea, 16 (29.1) cases of headacheTable 1.Adverse effects associated with Trigonella foenum-graecum (fenugreek) in clinical trialsThese reported adverse effects included gastrointestinal complications, such as reflux, abdominal pain, diarrhea, mild abdominal distention, hunger, appetite loss, and nausea. Other complications included migraine exacerbation, maple syrup odor in urine or sweat, frequent urination, dizziness, increased need for sanitary napkins, and hypoglycemia. The most prevalent adverse effect was urine with a maple syrup odor. The treatment duration varied across studies, ranging from a single dose of fenugreek leaf aqueous extract to a 12-week regimen of fenugreek seed capsules. As shown in table 2,, 23 clinical trial articles reported no adverse effects. The majority of these studies investigated type 2 diabetes and utilized fenugreek seed powder.Authors/ year of publicationCountry Number of participants in the fenugreek groupHealth status of the fenugreek groupPreparation and dosageDuration of the treatmentShamshad et al., 2016 44, India44Involved in menopausal symptoms250 mg capsules of fenugreek seed extract twice a day for a week and four times a day for 12 weeks90 daysSwaroop et al., 2015 45, USA50Polycystic ovary500 mg capsules of fenugreek seed extract two times a day90 daysNathan et al., 2013 46, India 25Parkinson300 mg of fenugreek seed extract two times a day6 monthsFlorentin et al., 2019 47, Greece50Pre-diabetesTablets containing bergamot extract 500 mg, fenugreek seed extract 200 mg, and olive leaf extract 100 mg once a day6 monthsVerma et al., 2016 48, India 77Type 2 diabetes500 mg capsules of fenugreek seed extract two times a day90 daysGeberemeskel et al., 2019 49, Ethiopia57Type 2 diabetes25 mg of fenugreek seed extract solution two times a day1 monthMadar et al., 1988 50, Israel21Type 2 diabetes15 g of fenugreek seeds mixed with water7 daysYounesy et al., 2014 51, Iran 51Dysmenorrhea900 mg capsules of fenugreek seed powder three times a dayThe first three days of menstruationLosso et al., 2009 52, USA10Type 2 diabetes9% of bread wheat flour replaced with 2.5 g of fenugreek seed powder (1 slice, two times a day)1 weekInanmdar et al., 2016 53, India 20Primary dysmenorrheaThree capsules equivalent to 3 g of fenugreek seedsThe first 3 days of menstruationPark et al., 2018 54, Korea44Testosterone deficiency syndrome200 mg capsules of fenugreek seeds two times a day8 weeksHassanzadeh et al., 2013 55, Iran23Polycystic ovary500 mg capsules of fenugreek seed extract two times a day2 monthsRao et al., 2016 56, Australia55Healthy men600 mg daily fenugreek seed extract12 weeksMaheshwari et al., 2017 57, India50Healthy men500 mg capsules of fenugreek seeds after breakfast12 weeksRao et al., 2020 31, Australia40Type 2 diabetes mellitusUsed two chapatis twice a day, 6 days/week for a daily dose of 5.45&,#8197 g of an Nigella sativa /fenugreek combination 12 weeksHausenblas et al., 2021 58, USA19Healthy menFenugreek 400 mg/d 60 daysZarghi et al., 2021 59, Iran 33Mechanically ventilated patients hospitalized3 mg of fenugreek seed powder with a gavage solution twice daily 5 daysForoumandi et al., 2023 60, Iran41Alzheimer&,rsquo s diseaseReceived 5 mL oral seed extract of fenugreek (equivalent to 500&,#8197 mg of dry extract) added to the similar routine treatment, including Donepezil (5 mg twice a day) and Sertraline (50&,#8197 mg once a day).4 monthsGupta et al., 2024 16, India42Type 2 diabetesUse 1000 mg (500 mg&,times 2) daily (Fenfuro&,reg ) capsules, that was a novel Fenugreek seed extract with &,gt 45% furostanolic saponins12 weeksLee-&,Oslash deg&,aring rd et al., 2024 61, Norway600 mg (n=21), 1200 mg (n=25) and 1800 mg (n=27)Men with reduced energy and libido related to non-optimal testosterone levelsTaking 3 tablets daily, 600 mg (n=21), 1200 mg (n=25), and 1800 mg (n=27) of fenugreek extract and essential nutrients.a12 weeksHota D et al., 2024 16, , 62, India204 (total patients)Type 2 diabetesFenfuro&,reg in the dosage of 500&,#8197 mg twice daily along with metformin12 weeksSingh et al., 2023 63, India113Pre-menopausal women with polycystic ovary syndrome (PCOS)Furocyst&,reg (2 capsules of 500&,#8197 mg/day)90 daysa. No reported side effects, but with a slight increase in serum concentrations of ALAT and creatinine |