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Exploring the Adverse Effects of Fenugreek in Humans: A Scoping Review

Document Type : Review Article

Authors

1 Department of Phytopharmaceuticals (Traditional Pharmacy), School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

3 Research Center for Traditional Medicine and History of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

4 Smart University of Medical Sciences, Tehran, Iran

5 Department of Medical Journalism, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

6 Department of Persian Medicine, School of Persian Medicine, Shahid Sadoughi University of Medical Sciences, Ardakan, Yazd, Iran

7 Department of Internal and Integrative Medicine, Evang. Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany

Abstract

Background: Trigonella foenum-graecum, commonly known as fenugreek, is used both as a spice and a medicinal herb. While numerous studies investigated its therapeutic effects, this scoping review aimed to explore the reported adverse effects associated with fenugreek consumption in humans. 
Methods: A systematic search of several scientific databases was conducted, including Google Scholar, Web of Science, PubMed/PMC-MEDLINE, Scopus, and Science Direct, from January 1990 to September 2024. The search utilized keywords such as “Fenugreek”, “Adverse Effects”, “Clinical Trial”, and “Case Report”, or “Case Series”. References of retrieved articles were also screened.
Results: The review included 60 articles. Of these, 14 clinical trials reported adverse effects, 23 reported none, and 13 did not provide information on adverse effects. Additionally, 10 case reports or case series (reported in eight articles) detailed allergic reactions or hypersensitivity signs and symptoms. The most common adverse effect was mild gastrointestinal discomfort following oral consumption. Other reported effects included hypoglycemia, potential hypokalemia, allergic reactions, a maple syrup odor in the urine, sweat, or skin of infants and mothers, and interactions with certain medications. 
Conclusion: Fenugreek is generally considered safe, with most reported side effects being mild and self-limiting. No fatalities have been attributed to its use. This evidence might be valuable for both the general public and healthcare professionals.

Highlights

Ehsan Amiri Ardekani (Google Scholar)
Mohammad Mahdi Parvizi (Google Scholar)

Keywords

What’s Known

Fenugreek (Trigonella foenum-graecum) is a plant that has been widely used both as a culinary spice and a medicinal herb.

What’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.

Introduction

In 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—when roasted—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 “Trigonellas,” “Trigonella foenum-graecum”, “Trigonella foenum graecum”, “Fenugreek”, “Fenugreeks”, “Foenumgraecum”, “Adverse Effects”, “Clinical Trial”, and “Case Report” and “Case Series” 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).

Results

Based 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 publication Country Participants Health status Preparation and dosage Duration of treatment Adverse effects reported from the fenugreek group Adverse effects reported in the control group
Steel et al., 2011 36 Australia 30 Healthy men Testophen tablets contain 300 mg of fenugreek powder two times a day 6 weeks Three cases of mild stomach pain before meals Was not observed
Rao et al., 2015 37 Australia 40 Women with low libido 600 mg of fenugreek seed extract per day In two consecutive menstrual periods Two cases of exacerbation of migraine, two cases of reflux Was not observed
Rao et al., 2020 31 Australia 50 Benign prostatic hyperplasia 600 mg of fenugreek seed extract per day 12 weeks Three cases of reflux One case of reflux
Najdi et al., 2019 38 Saudi Arabia 5 Type 2 diabetes that was treated with metformin 2 g of fenugreek in capsule form (one 500 mL capsule after breakfast, two capsules after lunch, and one capsule after dinner) 12 weeks One case of hypoglycemia Was not observed
Bumrungpert et al., 2018 32 Thailand 25 Lactating lady 3 capsules (200 mg fenugreek seeds, 120 mg ginger, 100 mg turmeric) 3 times a day 4 weeks Two cases of flatulence, two cases of urine with the odor of maple syrup Two cases of urine with the odor of maple syrup
Chevassus et al., 2009 33 France 24 Healthy Fenugreek tablets (one group, 588 mg, and another group, 1176 mg) 3-14 days with 14 days in between One case of heartburn, two cases of the specific smell of urine Was not observed
Chevassus et al., 2010 39 France 19 Overweight Fenugreek tablets contain 1176 mg of hydroalcoholic extract of fenugreek seeds daily 6 weeks Four cases of mild gastrointestinal symptoms, one case of a specific odor of urine and sweat Was not observed
Emtiazy et al., 2018 40 Iran 28 Mild asthma Ten mL of fenugreek seed extract syrup, two times a day 4 weeks Two cases of increased sanitary napkin use during menstruation Was not observed
Sharma et al., 1990 34 India 10 Type 1 diabetes 50 g of fenugreek seed powder, two times a day, at lunch and dinner, added to bread 10 days Four cases of gastrointestinal symptoms, including diarrhea and bloating Was not observed
Gupta et al., 2001 35 India 12 Type 2 diabetes 1 g of hydroalcoholic extract of fenugreek seeds in capsule form 2 months Five people with mild abdominal distension Was not observed
Abdel-Barry et al., 2000 30 Iraq 20 Healthy 40 mg per Kg bodyweight of fenugreek leaf extract in 10 mL of boiled water A single dose Four cases felt hungry, four cases of frequent urination, and four cases of dizziness. Was not observed
Lu et al., 2008 41 China 46 Type 2 diabetes Six 35% pills from seeds three times a day 12 weeks Two cases of nausea and one case of diarrhea Was not observed
Sudheeran et al., 2016 42  India 20 Healthy 500 mg capsules, including 300 mg of fiber and 200 mg of turmeric, two times daily before breakfast and at bedtime 30 days Two cases of decreased appetite One case of gastrointestinal problems
Mirgoaybayat et al., 43  Iran 55 Polycystic Ovary Syndrome Take 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 months Six (10.9%) cases of nausea 32 (58.2%) cases of nausea, 16 (29.1) cases of headache
Table 1.Adverse effects associated with Trigonella foenum-graecum (fenugreek) in clinical trials

These 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 publication Country Number of participants in the fenugreek group Health status of the fenugreek group Preparation and dosage Duration of the treatment
Shamshad et al., 2016 44 India 44 Involved in menopausal symptoms 250 mg capsules of fenugreek seed extract twice a day for a week and four times a day for 12 weeks 90 days
Swaroop et al., 2015 45 USA 50 Polycystic ovary 500 mg capsules of fenugreek seed extract two times a day 90 days
Nathan et al., 2013 46 India 25 Parkinson 300 mg of fenugreek seed extract two times a day 6 months
Florentin et al., 2019 47 Greece 50 Pre-diabetes Tablets containing bergamot extract 500 mg, fenugreek seed extract 200 mg, and olive leaf extract 100 mg once a day 6 months
Verma et al., 2016 48 India 77 Type 2 diabetes 500 mg capsules of fenugreek seed extract two times a day 90 days
Geberemeskel et al., 2019 49 Ethiopia 57 Type 2 diabetes 25 mg of fenugreek seed extract solution two times a day 1 month
Madar et al., 1988 50 Israel 21 Type 2 diabetes 15 g of fenugreek seeds mixed with water 7 days
Younesy et al., 2014 51 Iran 51 Dysmenorrhea 900 mg capsules of fenugreek seed powder three times a day The first three days of menstruation
Losso et al., 2009 52 USA 10 Type 2 diabetes 9% of bread wheat flour replaced with 2.5 g of fenugreek seed powder (1 slice, two times a day) 1 week
Inanmdar et al., 2016 53 India 20 Primary dysmenorrhea Three capsules equivalent to 3 g of fenugreek seeds The first 3 days of menstruation
Park et al., 2018 54 Korea 44 Testosterone deficiency syndrome 200 mg capsules of fenugreek seeds two times a day 8 weeks
Hassanzadeh et al., 2013 55 Iran 23 Polycystic ovary 500 mg capsules of fenugreek seed extract two times a day 2 months
Rao et al., 2016 56 Australia 55 Healthy men 600 mg daily fenugreek seed extract 12 weeks
Maheshwari et al., 2017 57 India 50 Healthy men 500 mg capsules of fenugreek seeds after breakfast 12 weeks
Rao et al., 2020 31 Australia 40 Type 2 diabetes mellitus Used two chapatis twice a day, 6 days/week for a daily dose of 5.45 g of an Nigella sativa /fenugreek combination 12 weeks
Hausenblas et al., 2021 58 USA 19 Healthy men Fenugreek 400 mg/d 60 days
Zarghi et al., 2021 59 Iran 33 Mechanically ventilated patients hospitalized 3 mg of fenugreek seed powder with a gavage solution twice daily 5 days
Foroumandi et al., 2023 60 Iran 41 Alzheimer’s disease Received 5 mL oral seed extract of fenugreek (equivalent to 500 mg of dry extract) added to the similar routine treatment, including Donepezil (5 mg twice a day) and Sertraline (50 mg once a day). 4 months
Gupta et al., 2024 16 India 42 Type 2 diabetes Use 1000 mg (500 mg×2) daily (Fenfuro®) capsules, that was a novel Fenugreek seed extract with >45% furostanolic saponins 12 weeks
Lee-Ødegård et al., 2024 61 Norway 600 mg (n=21), 1200 mg (n=25) and 1800 mg (n=27) Men with reduced energy and libido related to non-optimal testosterone levels Taking 3 tablets daily, 600 mg (n=21), 1200 mg (n=25), and 1800 mg (n=27) of fenugreek extract and essential nutrients.a 12 weeks
Hota D et al., 2024 16 , 62 India 204 (total patients) Type 2 diabetes Fenfuro® in the dosage of 500 mg twice daily along with metformin 12 weeks
Singh et al., 2023 63 India 113 Pre-menopausal women with polycystic ovary syndrome (PCOS) Furocyst® (2 capsules of 500 mg/day) 90 days
a. No reported side effects, but with a slight increase in serum concentrations of ALAT and creatinine
 Table 2.Clinical trials with no associated adverse effects from Trigonella foenum-graecum (fenugreek) administration

Research on the effects of fenugreek has been conducted across diverse populations. These included studies on individuals with dysmenorrhea (n=3), polycystic ovary syndrome (n=2), Parkinson’s disease (n=1), pre-diabetes (n=1), and testosterone deficiency (n=1), as well as on healthy men (n=2) and mechanically ventilated patients (n=1). The duration of these interventions ranged from 3 days to 6 months.

As shown in table 3, 13 clinical trials on fenugreek consumption, involving over 500 participants, reported no adverse effects. The studies investigated a range of health conditions, including type 2 diabetes, obesity, menopausal symptoms, hernia surgery, lactation, low libido in women, and gingivitis.

Authors/ year of publication Country Fenugreek group participant Health status of the fenugreek group Preparation and dosage Duration of the treatment
Robert et al., 2016 64 Malaysia 10 Healthy Buns and flatbreads each contain 10% fenugreek seed powder with 50 g of glucose and 250 mL of water daily. 6 times
Sundaram et al., 2018 65 India 40 Uncontrolled type 2 diabetes treated with metformin, with chronic periodontal disease 12.5 g of fenugreek powder before breakfast and lunch 1 month
Ansari et al., 2019 66 Iran 30 After transdermal local patch hernia surgery 10% fenugreek daily 2 days
Bordia et al., 1997 67 India 20 Non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease 2.5 g twice a day 3 months
India 20 Non-insulin-dependent diabetes mellitus (NIDDM) without coronary artery disease 2.5 g twice a day 3 months
India 20 Healthy 2.5 g twice a day 3 months
Ghasemi et al., 2015 27 Iran 39 Healthy breastfeeding mothers 7.5 g of fenugreek seed powder with 3 g of black tea three times a day 4 weeks
Kassaian et al., 2009 68 Iran 11 Type 2 diabetes 10 g of fenugreek seed powder soaked in water daily 8 weeks
Kassaian et al., 2009 68 Iran 7 Type 2 diabetes 10 g of fenugreek seed powder in yogurt daily 8 weeks
Ranad et al., 2017 69 India 30 Type 2 diabetes 10 g of fenugreek seeds soaked in water 6 months
Kiss et al., 2018 70 Hungary 8 Healthy 500 mg capsules, the first day two capsules in two meals at noon and evening, the last day two capsules in the evening, and on other days two capsules three times a day 11 days
Mathern et al., 2009 71 USA 18 Fat Extracts of 4 and 8 g of fenugreek fiber in beer 3 days
Steels et al., 2017 72 Australia 54 Menopausal symptoms 600 mg of seed extract without fenugreek pod daily 12 weeks
Palacios et al., 2019 73 Spain 29 Women with low libido Tablets contain 300 mg of fenugreek extract two times a day 2 months
Mehrzadi et al., 2020 74 Iran 150 Type 2 diabetes Traditional herbal capsules including 115 mg fenugreek, caper, rosehip, Securigera securidaca, Silybum marianum (milk thistle), nettle, and Caucasian whortleberry daily 3 months
Varghese et al., 2021 75 Karnataka 15 Gingivitis Use toothpaste daily, two times (morning and at night) in a pea-size amount 14 days
Table 3.Clinical trials of Trigonella foenum-graecum (fenugreek), not reporting adverse effects

The duration of these studies varied, with the shortest being a two-day investigation using a 10% fenugreek transdermal patch on hernia surgery wounds. The longest was a 6-month trial involving patients with type 2 diabetes.

Case Reports and Case Series Articles

As detailed in table 4, ten case reports were qualified, reviewed, and analyzed. The cases involved seven females and three males, with ages ranging from infancy to 67 years.

Authors/ year of publication Country Sex Age Health status How to expose Adverse effects Result
Patil et al., 1997 76 India Woman 37 Mild asthma - pea allergy Open and smell the glass containing fenugreek Runny nose and eyes, cough, fainting Treated
Patil et al., 1997 76 India Woman 45 Asthma - Dandruff with a history of wheezing after eating fenugreek Fenugreek seed ointment on the scalp Angioedema of the face, runny nose, and numbness of the head Treated
Bentele-Jaberg et al., 2015 77 Switzerland Woman 32 1 month after delivery Eat medicine made from fenugreek seeds Blisters and sores on the face and upper body, with involvement of the mouth, lips, and tongue Treated
Joseph et al., 2018 78 USA Man 14 Healthy Eat food containing fenugreek Urticaria, chest tightness, abdominal pain, vomiting Treated
Korman et al., 2001 79 Israel Man Infant Healthy The baby’s mother consumed fenugreek in the first hours of labor pains The smell of maple syrup from the skin and diaper area Treated
Lambert et al., 2001 80 Canada Woman 67 Atrial fibrillation on warfarin A fenugreek capsule with ten drops of Boldo after a meal Increase INR Treated
Aurich et al., 2019 81 Germany Woman 34 Atopic dermatitis, asthma, peanut allergy Eat a Chinese soup containing fenugreek Facial flushing, angioedema, shortness of breath, nausea, and diarrhea Treated
Doolabh et al., 2019 82 Australia Woman 38 Psychosis on sertraline during breastfeeding Use fenugreek supplements to increase breastfeeding Symptoms of serotonin syndrome include hyperreflexia, nausea, anxiety, and tachycardia Treated
Ohnuma et al., 1998 83 Japan Woman 26 Healthy Use curry powder containing fenugreek Itching, diarrhea, wheezing Treated
Ebo et al., 2006 84 Belgium Man 25 Healthy with a history of allergies to fenugreek and coriander in occupational exposure Eat a loaf of bread containing fenugreek and coriander Anaphylactic reactions include generalized urticaria, conjunctivitis, bronchospasm angioedema Treated
Table 4.Reported adverse events of Trigonella foenum-graecum (fenugreek) in case reports and series

The most commonly reported adverse effects of fenugreek were allergic reactions, including pruritus, shortness of breath, rhinorrhea, diarrhea, angioedema, cough, and anaphylaxis (seven cases). Almost all cases reported a history of allergies to other substances, such as peas, peanuts, and coriander. In one case, the topical application of a fenugreek ointment to the scalp for dandruff resulted in syncope.

One case of Stevens-Johnson syndrome and toxic epidermal necrosis was reported in a 32-year-old woman. The reaction, presenting as blisters and sores on her face and upper torso, occurred 1 month postpartum after she had taken a fenugreek-containing medication to stimulate lactation.

In another report, a newborn boy exhibited a maple syrup odor from his skin and diaper area after his mother had consumed fenugreek during early labor.

Another case described a 67-year-old woman with atrial fibrillation whose international normalized ratio (INR) increased following the consumption of fenugreek and Boldo drops while on warfarin therapy.

In another report, symptoms suggestive of serotonin syndrome, including hyperreflexia, tachycardia, nausea, and anxiety, were observed in a 38-year-old woman with psychosis. The symptoms emerged after she consumed a fenugreek supplement to augment lactation while taking sertraline and breastfeeding.

Discussion

The utilization of herbal remedies, herbal medicinal products, and supplements has surged significantly over the past three decades. It is estimated that at least 80% of the world’s population relies on these products for several aspects of healthcare, including preventive, therapeutic, or palliative care. 85 , 86 The use of herbal products is deeply entrenched in the traditional medicinal practices of many cultures for disease prevention and treatment. 87 Although the World Health Organization (WHO) acknowledges herbal products as a vital component of the healthcare system, growing apprehensions exist regarding their quality and safety. 88 Herbal products are generally not subject to stringent regulation, as they are often classified as dietary supplements, thereby evading the rigorous scrutiny required for pharmaceutical drugs. Despite a widespread public perception that herbal remedies are inherently safe, numerous studies indicated that they could cause mild to severe, clinically significant adverse effects. 28 , 89

Nowadays, the market for non-registered health-related products consists primarily of herbal remedies and food supplements. In this context, official or governmental systems often fail to comprehensively document their adverse effects, which are typically reported on a case-by-case basis. Research revealed that consumers might experience adverse events from herbal food supplements, particularly when they received insufficient information about these products. 90 - 93

Fenugreek is commonly used as a food flavoring and is also consumed traditionally to prevent or treat certain diseases. 94 , 95 While numerous systematic reviews have examined its efficacy 19 , 96 , 97 and toxicity, 98 no previous review has specifically focused on its adverse effects. This study is the first to systematically extract and summarize the adverse effects reported across various study types. This study illustrated the potential negative consequences associated with fenugreek consumption.

The most significant and well-documented adverse effects were allergic and hypersensitivity reactions, including angioedema, anaphylaxis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The clinical significance of these reactions is underscored by their documentation in dedicated case reports and case series. Other less common but notable adverse effects included serotonin syndrome, a maple syrup odor in infants, elevated INR level, dizziness, syncope, and other similar symptoms. However, the most frequently reported adverse effects were gastrointestinal problems, which were often mild and required no treatment. According to the included articles, all patients who experienced adverse effects from fenugreek recovered completely, with many cases resolving without intervention.

Several mechanisms could be suggested for the adverse effects associated with fenugreek. Gastrointestinal effects, such as indigestion, abdominal distention, and bloating, are likely attributable to its high fiber content. 99 This high fiber content may also interfere with the absorption of concurrently administered oral medications. Consequently, it is advisable to avoid combining fenugreek with oral drugs, particularly those with a narrow therapeutic index. The hypoglycemic activity of fenugreek, which occurs through the stimulation of insulin signaling pathways 100 and the inhibition of carbohydrate digestion and absorption by its soluble dietary fiber, 101 poses a risk of hypoglycemia. Therefore, diabetic patients should use fenugreek with caution, and long-term use might necessitate an adjustment of their insulin dose. Moreover, fenugreek consumption was associated with reduced serum levels of potassium. 76 Evidence showed that when used concomitantly with diuretics or other hypokalemic agents, fenugreek might potentially contribute to hypokalemia. 102 , 103

Dizziness associated with fenugreek use might result from a significant decrease in systolic blood pressure 101 or from hypoglycemia-induced neurological symptoms due to its activity on insulin receptors. 22 Moreover, concomitant use of fenugreek with antiarrhythmic drugs, diuretics, laxatives, or mineralocorticoids might increase the risk of hypokalemia and potentiate cardiac glycoside toxicity. Fenugreek seed extracts exhibited both central nervous system (CNS) stimulant and depressant activities, 77 , 78 which could potentially trigger seizures in individuals with epilepsy.

The most frequently reported significant complications were allergic reactions to fenugreek. 76 - 78 , 81 , 83 , 84 As fenugreek belongs to the Fabaceae family, individuals with allergies to peanuts, peas, or coriander should use it with caution due to the potential for cross-reactivity. Fenugreek might also interact with serotonergic drugs, such as selective serotonin reuptake inhibitor (SSRI), increasing the risk of serotonin syndrome. 82 A case report noted that fenugreek could elevate the INR, a critical consideration for patients taking warfarin. 80 A rare, benign, yet well-documented effect is a maple syrup odor in the urine or sweat of infants or mothers following maternal consumption. 79 Finally, the safety of long-term fenugreek use remains uncertain due to a lack of extensive studies.

This study had several limitations. As a scoping review, it did not incorporate critical steps of a systematic review, such as a formal quality assessment of the included studies, an evaluation of the risk of bias, or the use of independent reviewers for article selection and data extraction. Furthermore, the overall quality of the evidence was not assessed using a tool such as GRADE. The review was also limited by its exclusion of animal studies, experimental studies, case-control studies, cross-sectional studies, and cohort studies. Consequently, the authors recommend that future research consider these limitations.

It is important to note that a meta-analysis was not an objective of this study. In addition, while some of the included studies did not report any adverse events, this could not be taken as definitive proof of their absence. The authors suggested that a future systematic review and meta-analysis (including network meta-analysis) could provide more robust insights into the adverse effects of fenugreek and its supplements. Finally, further studies are strongly recommended to investigate the mechanisms underlying fenugreek’s adverse effects and to assess the relationship between dosage, severity, and the incidence of these side effects.

Conclusion

Fenugreek and its supplements are commonly used worldwide as both a vegetable and an herbal remedy. Although widely perceived as safe, several studies demonstrated that it could cause adverse effects, including allergic and hypersensitivity reactions, gastrointestinal complaints, headache, dizziness, hypoglycemia, elevated INR levels in plasma, and hypokalemia. However, it is crucial to note that no documented fatalities or cases requiring aggressive medical intervention were attributed to fenugreek use.

Acknowledgment

The authors extend their gratitude to the Vice-Chancellor for Research of Shiraz University of Medical Sciences (Shiraz, Iran) for supporting this study (Grant no: 95-01-01-11487). This manuscript is extracted from the doctoral thesis of Asma Homaee, which was completed in partial fulfillment of the requirements for the Medical Doctor degree at Shiraz University of Medical Sciences.

Authors’ Contribution

E.AA: Study design, conception, data gathering, data analysis, data interpretation, drafting and reviewing critically; MM.P: Study design, data analysis, data interpretation, and reviewing critically; R.Z: Data analysis and drafting; M.MJ: Data gathering and drafting; Th.R: Study design and reviewing critically; M.P: Study design, conception, data gathering, data analysis, data interpretation and reviewing critically; All authors approved the final the version of the manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of AI

Artificial intelligence (QuillBot) was used solely for language editing. The authors are fully responsible for the content and integrity of the manuscript.

Conflict of Interest

None declared.

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Iranian Journal of Medical Sciences
Volume 51, Issue 1
January 2026
Pages 4-18
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History
  • Received: 01 March 2025
  • Revised: 02 May 2025
  • Accepted: 28 June 2025
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