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Received: 2 October 2019 Revised: 1 December 2019 Accepted: 14 January 2020

DOI: 10.1002/ptr.6627

REVIEW

Effect of fenugreek extract supplement on testosterone levels


in male: A meta-analysis of clinical trials

Anahita Mansoori1 | Seyedahmad Hosseini1,2 | Marzie Zilaee1,2 |


Razie Hormoznejad3 | Mojdeh Fathi3

1
Nutrition and Metabolic Diseases Research
Center, Ahvaz Jundishapur University of Different types of glycosides extract of fenugreek have shown androgenic and ana-
Medical Sciences, Ahvaz, Iran
bolic effect in male. The aim of the study was to evaluate the effect of fenugreek
2
Nutrition Department, Faculty of
Paramedicine, Ahvaz Jundishapur University of extract on total testosterone levels in male. Medline via PubMed, Scopus databases,
Medical Sciences, Ahvaz, Iran Cochrane Library, Web of Science, and Google Scholar were searched up to
3
Department of Community Nutrition, School
November 2018 for randomized clinical trials comparing intake of fenugreek extract
of Nutrition and Food Science, Isfahan
University of Medical Sciences, Isfahan, Iran with control group. Data on change in serum total testosterone were pooled using
random-effects models. A total of four trials were included. Fenugreek extract has a
Correspondence
Mojdeh Fathi, Department of Community significant effect on total serum testosterone. Results from clinical trials suggest that
Nutrition, School of Nutrition and Food
fenugreek extract supplement has an effect on serum total testosterone levels
Science, Isfahan University of Medical
Sciences, Isfahan, Iran. in male.
Email: mojdeh68.fathi@yahoo.com
KEYWORDS
Funding information
Ahvaz Jundishapur University of Medical fenugreek extract, total testosterone
Sciences

1 | I N T RO DU CT I O N improving muscle strength. Studies indicated decreasing protein syn-


thesis and muscle strength and elevated adiposity in male testoster-
Testosterone as the main sexual men hormone is responsible for the one deficiency (Aydogan et al., 2012; Basualto-Alarcón, Jorquera,
development of male reproductive tissues and anabolic functional in Altamirano, Jaimovich, & Estrada, 2013).
men. Evidences have well indicated that serum total testosterone Because of the adverse effects of anabolic steroids, today, com-
declines gradually with age(Fabbri et al., 2016). The prevalence of panies are trying to produce nutritional supplement containing ergo-
men testosterone deficiency is reported at 2.1–5.7% in ages genic components. Fenugreek seed extract is certificated by the
49–79 years (Wu et al., 2010). The main clinical manifestations of low U.S. Food and Drug Administration.
serum total testosterone include decreased libido, erectile dysfunc- Some animal and human studies introduced fenugreek (Trigonella
tion, fatigue and negative mood states. Secondary outcomes of tes- foenum-graecum) extract as a food supplement boosting testosterone
tosterone deficiency are changes in body composition, including (Aswar, Bodhankar, Mohan, & Thakurdesai, 2010; Hamden et al.,
increasing fat mass, decreasing lean body mass and bone mineral den- 2010; Heufelder et al., 2009; Nguyen, Ko Ko, Sattar, Gucuk Ipek, &
sity and as well as loss of muscle mass and strength (Dandona & Ali, 2017). But the results of these studies are not consistent.
Rosenberg, 2010; Kaufman & Vermeulen, 2005; Wang et al., 2000; Recently, studies investigated the benefit effects of prohormone com-
Zitzmann, Faber, & Nieschlag, 2006). Also, studies showed a signifi- ponents, which are found in fenugreek seed extract, on hormonal-
cant relationship between testosterone deficiency and metabolic syn- related status like male impotence and galactagogue in lactating
drome (Heufelder, Saad, Bunck, & Gooren, 2009; Qing et al., 2017). women. Researchers proposed that fenugreek seed extract elevates
Moreover, testosterone is important for athletic performance because testosterone levels through several mechanisms. Some studies
of its anabolic and consciousness properties. Testosterone lead to suggested boosting androgenic activity due to sapogenins glycosides
positive balancing nitrogen through increasing protein synthesis and in fenugreek seed extract, and another study showed the efficacy of
declining protein breakdown, resulting in muscle hypertrophy and fenugreek extract on aromatase and 5-alpha-reductase inhibition

Phytotherapy Research. 2020;1–6. wileyonlinelibrary.com/journal/ptr © 2020 John Wiley & Sons, Ltd. 1
2 MANSOORI ET AL.

(Wankhede, Mohan, & Thakurdesai, 2016; Wilborn et al., 2010b). of participants, mean age, duration of supplementation, interventions,
Therefore, in the present meta-analysis of clinical trial studies, we pur- and outcome characteristics (differences between baseline and final
pose to obtain a single summary estimate of the effect of ethanolic mean and SD values of serum total testosterone levels). Graphical data
extract of fenugreek seeds on the testosterone level in males. were converted to numerical data using Graph Digitizer 2.26 software
(Wilborn et al., 2010a).

2 | MATERIAL AND METHODS


2.4 | Quality assessment
This meta-analysis was designed and performed in late 2018 to inves-
tigate and analysis results of effect of fenugreek extract on total tes- Two reviewers (MF and AM) assessed the quality of the evidences
tosterone levels in male. The meta-analysis has been registered in the using the Cochrane risk of bias assessment tool, independently. Seven
International Prospective Register Of Systematic Review (PROSPERO items considered random sequence generation, allocation conceal-
number: CRD42019122265). ment, blinding of participants and outcome assessment, selective
reporting, and other bias.

2.1 | Search strategy


2.5 | Statistical analysis
To collect data, we searched PubMed, Scopus databases, Cochrane
Library, Web of Science, and Google Scholar. The strategies were con- The data analysis was carried out using the STATA 14.0 software
structed based on PICO (i.e., patient, intervention, comparator, and (Stata, College Station, TX, USA). The effect of fenugreek extract sup-
outcome). Reference lists of all relevant studies and review articles plement on testosterone levels was calculated by the weighted mean
were searched manually to find additional studies. difference (WMD) with associated 95% confidence intervals. If the
The search terms were fenugreek (“fenugreek” OR “trigonella”) mean serum testosterone was not stated in the studies, the mean and
AND experimental study design (“trial” OR “clinical trial” OR “interven- SD of serum testosterone was calculated by following formulas. Mean
tion”), AND testosterone (“Testosterone” OR “total testosterone” OR (change) = Mean (Final) − Mean (baseline),
“sex hormone” OR “libido” OR “sperm”), AND (“resistance training”
OR “sport”) to identify reports of randomized control trials (RCTs) that SD ðchangeÞ =
reported the effect of fenugreek extract on serum total testosterone pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ðSD baselineÞ2 + ðSD finalÞ2 −ð2 × :5 × SD baseline × SD finalÞ:
levels in male.

The heterogeneity among studies was investigated by χ 2 test.


2.2 | Study selection Fixed effect model was performed when p > .1 and I2 < 50% and ran-
dom effect model was performed when p < .1 or I2 ≥ 50% on the con-
All studies were identified from database imported to End Note X7, trary. P values <.05 with 95% confidence interval were considered
and duplicate studies were removed. The selected studies were statistically significant for the statistic test.
checked out based on title and abstract (MF, RH). The full text of
the remaining papers was screened again by a reviewer. We evalu-
ated the efficacy of fenugreek extract supplementation on total tes- 3 | RE SU LT S
tosterone levels by comparing the effects of fenugreek extract at
any dosage with placebo or no intervention group. All RCTs publi- 3.1 | Study selection
shed in English were conducted on healthy male subjects more than
18 years old. The exclusion criteria included not randomized, not We identified 29 relevant studies through searching in title and
clinical, and no control group studies; the combination of fenugreek abstract and checking the references. After removing duplicates,
extract with other complementary therapies; short duration of study 19 articles were potentially relevant. Four studies were completed but
(<4 weeks); and the studies that did not report the required data for not published, and the authors did not send the results of their studies
analyzing. for us (The Efficacy Study of FUROSAP: A Testosterone Booster Supple-
ment in Humans [ClinicalTrial.gov], Evaluation of Furosap in Human Vol-
unteers [ClinicalTrial.gov], The Efficacy of Fenugreek Supplementation on
2.3 | Data extraction Men’s Health [ClinicalTrial.gov], and Efficacy of Fenugreek Seed and Les-
pedeza cuneata in TDS; ClinicalTrial.gov). Eleven studies were excluded
Two reviewers (MF and AM) independently extracted the suitable based on the study inclusion and exclusion criteria. The remaining four
data by using a standardized data collection including the full name of studies were regarded potentially for the meta-analysis. The results of
the first author, publication date, study design, origin country, number search strategy are shown in Figure 1.
MANSOORI ET AL. 3

FIGURE 1 Diagram of study


selection

TABLE 1 Characteristics of the studies included

Number of
Mean participants
Author age (intervention/ Fenugreek type and dose Placebo type and Duration
(year) Country Subject (year) control) (Intervention) dose (Control) (weeks)
Guo (2018) Albany Healthy male 24.02 12/12 Furosap capsules NR 250 mg/day 12
athletes 250 mg/day
Rao (2016) Australia Healthy male 55.6 47/50 Fenugreek seed extract NR 12
600 mg/day
Wankhede India Healthy male 22.04 29/26 glycoside fraction of di-calcium 8
et al. fenugreek seeds phosphate
(2016) 2*300 mg/day 2*300 mg/day
Wilborn USA Resistance-trained 21 17/13 Fenugreek capsule Maltodextrin 8
(2010) men 500 mg/day 500 mg/day
4 MANSOORI ET AL.

F I G U R E 2 Forest plot of mean difference of


changes in serum total testosterone level. WMD,
weighted mean difference; CI, confidence interval

TABLE 2 Quality of the four studies included in the meta-analysis, as assessed by the Cochrane collaboration tool

Random Blinding of Free of


sequence Allocation Blinding of outcome Follow-up selective Free of
Reference generation concealment participants assessment >80% reporting other bias
Amanda Rao + + + + + ? +
et al. (2016)
Rui Guo et al. + + ? ? + ? +
(2018)
Sachin + + + ? + ? +
Wankhede
et al. (2016)
Colin Wilborn + + + ? ? ? +
et al.(2010)

Note: + means low risk/high risk and ? means unclear.

3.2 | Characteristics of the studies included There was heterogeneity between the trials (Q = 16.28; df = 3;
p = .001; I2 = 81.6%).
We identified a total of 206 participants, 105 individuals on interven- We used random effect to evaluate serum total testosterone
tion and 101 on placebo, from the four included eligible RCTs. All the levels due to the significant heterogeneity.
relevant studies that were published from the inception of databases The quality for each trial of the included studies is presented in
until November 2018 were assessed. Because of the importance of tes- Table 2.
tosterone effects on muscle performance, several studies evaluated the
effect of fenugreek extract in training male. So participants were
included in the study including all healthy training and non-training 4 | DI SCU SSION
male. All included studies did not show any harmful side effects of fenu-
greek extract. Details of included studies are shown in Table 1. In the present meta-analysis of the four clinical trials, fenugreek
extract supplement has significant effect on serum total testosterone
levels. Fenugreek is an annual plant in many parts of the world. Its
3.3 | Effect of fenugreek extract on total leaves, seeds, and roots are used as spice, herb, and vegetable
testosterone levels (Adamska & Lutomski, 1971; Bahmani, Shirzad, Mirhosseini,
Mesripour, & Rafieian-Kopaei, 2016; Yadav & Baquer, 2014). Studies
There was a significant effect of the rise in total testosterone levels in indicated remedy effect of Fenugreek on hypercholesterolemia and
the fenugreek extract group. In comparison with placebo group, the hyperglycemia in diabetes and prediabetes patients (Gong et al.,
mean total testosterone levels in the subjects receiving fenugreek 2016). Other results has shown that Fenugreek reduced liver
extract was higher (WMD = 0.85 95% CI [0.10, 1.60]; p = .026; enzymes, lipid accumulation, and ethanol-induced toxicity in liver
Figure 2). (Al-Wabel, Mousa, Omer, & Abdel-Salam, 2008; Kaviarasan,
MANSOORI ET AL. 5

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national Journal of Pharmacology, 4, 135–139.
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