Fenugreek: New Therapeutic Resource or Emerging Allergen
Conditions: Fenugreek Hypersensitivity - Cross-reactivity - Food Allergy
Sponsor: Paola Miciullo

 
 
 
 
 
 
FENUGREEK: AN EMERGENT ALLERGEN 
NCT ID not yet assigned 
DATE: January 15, 2024 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Introduction 
Fenugreek or Trigonella foenum greacum is an ancient medicinal plant native to the eastern 
Mediterranean; it belongs to Rosaceae order, Leguminosae family, subfamily of Papilonaceae and it 
is used as a medicinal herb, spice or food.  
Fenugreek is a short-lived annual angiosperm plant, 50 cm tall; it has green trifoliate leaves, white 
or yellow flowers and thin, curved pods containing about 10-20 golden yellow seeds. Its name comes 
from the triangular shape of its flowers (from Latin "trigonum"). 
Fenugreek seeds are ground and the powder is used as a condiment or in traditional Ayurvedic and 
Chinese medicine. 
It is used in Indian cuisine as a component of spice mix, such as curry, instead in Egypt it is also used 
as a supplement in wheat and corn flour for bread-making. Fenugreek appears to have many health 
benefits and potential medicinal properties (antioxidant, antidiabetic, hepatoprotective, 
hypocholesterolemic, antimicrobial, anti- inflammatory, neuroprotective, anticarcinogenic, 
antiulcer, and antilithigenic) both in vitro and in vivo studies (Ouzir et al., 2016; Neelakantan et al., 
2014; Yadav et al., 2014; Nagulapalli Venkata et al., 2017). 
Fenugreek seed contains: soluble galactomannan, insoluble fiber, proteins, lipids, alkaloids 
(trigonelline), saponins (based on diosgenin and yamogenin), 4-hydroxyisoleu-cin, volatile oil and C- 
glycosylflavones of apigenin and luteolin (Yao et al., 2020). 
Specifically, it is mainly used to improve digestion, activate metabolism, facilitate delivery, and 
increase milk flow. Trigonelline appears to be the most active metabolite in fenugreek; it is useful in 
treating diabetes, reducing cholesterolemia, and treating cancers (liver, breast, cervix, and pancreas) 
as a phytohormone (Bahmani et al., 2016; Smith et al., 2003). 
In addition, fenugreek is used as a cut/crushed seed, herbal preparation, dry extract, soft extract, 
powder, or in combination with other substances; its main applications are appetite enhancement, 
topical treatment of localized inflammation of the skin and gut, as an adjuvant in diabetes or 
hypercholesterolemia. 
It is non-toxic up to the maximum dose of 5 g/kg weight. Side effects such as flatulence, diarrhea, 
abdominal distension, dyspepsia, hypokalemia, increased frequency of urination, and dizziness have 
been reported. 
Among immunologic adverse reactions, the literature reports mainly allergic reactions after contact 
or ingestion of fenugreek, characterized by urticaria, angioedema, dyspnea, cough, rhinorrhea, and 

itching. Type IV or delayed skin reactions following contact with fenugreek preparations are rare but 
possible. Finally, many authors report the known cross-reactivity between fenugreek and foods 
belonging to the legume (or Fabaceae) family (European Medicines Agency Assessment Report on 
Trigonella Foenum-Graecum L., Semen; 2018; Minciullo et al., 2017; Che et al., 2017; Vinje et al., 
2012). 
  
Purpose of the study 
Given that the use of fenugreek is increasing worldwide, both in diet and nutraceuticals, we can 
expect an increase in adverse reactions in the coming years. 
The purpose of this study is to analyze the medical history of patients who came to our operating 
unit for suspected adverse reactions after ingestion of fenugreek and to highlight possible cross-
reactivity between fenugreek and other legumes or other foods. 
 
Study design 
Type of the study 
The proposed study is observational, spontaneous, retrospective. 
 
Study location 
The study will be carried out at the A.O.U. "G. Martino" of Messina, Operative Unit of Allergy and 
Clinical Immunology. 
 
Possible benefits 
To assess the true incidence of sensitization to fenugreek in the population with clinical history 
indicative of allergy to spices or nutraceuticals containing this substance, since fenugreek is 
increasingly used both in food preparation and for therapeutic purposes. The finding of relevant 
allergenicity of fenugreek could prompt further study of molecular allergens useful for highlighting 
new patterns of cross-reactivity. 
 
Possible adverse effects 
None. 
 
 

Clinical Case History. 
As this is a retrospective study, the clinical case series consists of patients with history suggestive of 
allergic reaction to foods probably containing fenugreek, who are referred to the Operative Unit of 
Allergy and Clinical Immunology of the A.O.U. "G. Martino" of Messina on an outpatient visit during 
the period from January 2022 to December 2023 to perform skin prick tests for foods. 
 
Inclusion criteria. 
All patients over the age of 18 years, who came to the outpatient clinic of the Operative Unit of 
Allergy and Clinical Immunology for suspected allergic reaction after ingestion of spicy foods or 
intake of phytotherapeutic products containing fenugreek and were prick-by-prick tested with 
fenugreek, will be included. 
 
Exclusion criteria. 
All patients younger than 18 years of age and patients who came to the outpatient clinic of the 
Operative Unit of Allergy and Clinical Immunology for food allergy skin tests but were not tested for 
fenugreek because they had an inconclusive history will be excluded. 
 
OTHER INFORMATION 
Processing of personal and health data 
The personal, clinical and photographic data of the patients involved in the study will be processed 
in compliance with current regulations on privacy protection, according to the normal procedures 
already in place in the A.O.U. "G. Martino" of Messina. 
In addition, the patients, by means of special forms, duly filled out and signed, have given their 
consent to the processing of clinical data, including photographic or filmed images related to the 
health care services being processed anonymously for the purposes of clinical research, 
epidemiology, training and studies of pathologies. 
 
Costs 
No cost burden will be caused by the study to the National Health Service or to the A.O.U. "G. 
Martino" as no additional or different examinations from normal clinical practice are expected. 
 
 

Statistical analysis 
A descriptive analysis of the demographic and clinical characteristics of the subjects involved in the 
study will be performed. Categorical variables related to fenugreek-positive subjects and any other 
co-sensitizing allergens will be expressed as absolute and/or relative frequencies. 
 
Bibliography 
 
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