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Effect of fenugreek extract supplement on testosterone levels in male: A meta‐analysis of clinical trials

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Abstract

Different types of glycosides extract of fenugreek have shown androgenic and anabolic effect in male. The aim of the study was to evaluate the effect of fenugreek extract on total testosterone levels in male. Medline via PubMed, Scopus databases, Cochrane Library, Web of Science, and Google Scholar were searched up to November 2018 for randomized clinical trials comparing intake of fenugreek extract 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 significant effect on total serum testosterone. Results from clinical trials suggest that fenugreek extract supplement has an effect on serum total testosterone levels in male.
REVIEW
Effect of fenugreek extract supplement on testosterone levels
in male: A meta-analysis of clinical trials
Anahita Mansoori
1
| Seyedahmad Hosseini
1,2
| Marzie Zilaee
1,2
|
Razie Hormoznejad
3
| Mojdeh Fathi
3
1
Nutrition and Metabolic Diseases Research
Center, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
2
Nutrition Department, Faculty of
Paramedicine, Ahvaz Jundishapur University of
Medical Sciences, Ahvaz, Iran
3
Department of Community Nutrition, School
of Nutrition and Food Science, Isfahan
University of Medical Sciences, Isfahan, Iran
Correspondence
Mojdeh Fathi, Department of Community
Nutrition, School of Nutrition and Food
Science, Isfahan University of Medical
Sciences, Isfahan, Iran.
Email: mojdeh68.fathi@yahoo.com
Funding information
Ahvaz Jundishapur University of Medical
Sciences
Different types of glycosides extract of fenugreek have shown androgenic and ana-
bolic effect in male. The aim of the study was to evaluate the effect of fenugreek
extract on total testosterone levels in male. Medline via PubMed, Scopus databases,
Cochrane Library, Web of Science, and Google Scholar were searched up to
November 2018 for randomized clinical trials comparing intake of fenugreek extract
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
significant effect on total serum testosterone. Results from clinical trials suggest that
fenugreek extract supplement has an effect on serum total testosterone levels
in male.
KEYWORDS
fenugreek extract, total testosterone
1|INTRODUCTION
Testosterone as the main sexual men hormone is responsible for the
development of male reproductive tissues and anabolic functional in
men. Evidences have well indicated that serum total testosterone
declines gradually with age(Fabbri et al., 2016). The prevalence of
men testosterone deficiency is reported at 2.15.7% in ages
4979 years (Wu et al., 2010). The main clinical manifestations of low
serum total testosterone include decreased libido, erectile dysfunc-
tion, fatigue and negative mood states. Secondary outcomes of tes-
tosterone deficiency are changes in body composition, including
increasing fat mass, decreasing lean body mass and bone mineral den-
sity and as well as loss of muscle mass and strength (Dandona &
Rosenberg, 2010; Kaufman & Vermeulen, 2005; Wang et al., 2000;
Zitzmann, Faber, & Nieschlag, 2006). Also, studies showed a signifi-
cant relationship between testosterone deficiency and metabolic syn-
drome (Heufelder, Saad, Bunck, & Gooren, 2009; Qing et al., 2017).
Moreover, testosterone is important for athletic performance because
of its anabolic and consciousness properties. Testosterone lead to
positive balancing nitrogen through increasing protein synthesis and
declining protein breakdown, resulting in muscle hypertrophy and
improving muscle strength. Studies indicated decreasing protein syn-
thesis and muscle strength and elevated adiposity in male testoster-
one deficiency (Aydogan et al., 2012; Basualto-Alarcón, Jorquera,
Altamirano, Jaimovich, & Estrada, 2013).
Because of the adverse effects of anabolic steroids, today, com-
panies are trying to produce nutritional supplement containing ergo-
genic components. Fenugreek seed extract is certificated by the
U.S. Food and Drug Administration.
Some animal and human studies introduced fenugreek (Trigonella
foenum-graecum) extract as a food supplement boosting testosterone
(Aswar, Bodhankar, Mohan, & Thakurdesai, 2010; Hamden et al.,
2010; Heufelder et al., 2009; Nguyen, Ko Ko, Sattar, Gucuk Ipek, &
Ali, 2017). But the results of these studies are not consistent.
Recently, studies investigated the benefit effects of prohormone com-
ponents, which are found in fenugreek seed extract, on hormonal-
related status like male impotence and galactagogue in lactating
women. Researchers proposed that fenugreek seed extract elevates
testosterone levels through several mechanisms. Some studies
suggested boosting androgenic activity due to sapogenins glycosides
in fenugreek seed extract, and another study showed the efficacy of
fenugreek extract on aromatase and 5-alpha-reductase inhibition
Received: 2 October 2019 Revised: 1 December 2019 Accepted: 14 January 2020
DOI: 10.1002/ptr.6627
Phytotherapy Research. 2020;16. wileyonlinelibrary.com/journal/ptr © 2020 John Wiley & Sons, Ltd. 1
(Wankhede, Mohan, & Thakurdesai, 2016; Wilborn et al., 2010b).
Therefore, in the present meta-analysis of clinical trial studies, we pur-
pose to obtain a single summary estimate of the effect of ethanolic
extract of fenugreek seeds on the testosterone level in males.
2|MATERIAL AND METHODS
This meta-analysis was designed and performed in late 2018 to inves-
tigate and analysis results of effect of fenugreek extract on total tes-
tosterone levels in male. The meta-analysis has been registered in the
International Prospective Register Of Systematic Review (PROSPERO
number: CRD42019122265).
2.1 |Search strategy
To collect data, we searched PubMed, Scopus databases, Cochrane
Library, Web of Science, and Google Scholar. The strategies were con-
structed based on PICO (i.e., patient, intervention, comparator, and
outcome). Reference lists of all relevant studies and review articles
were searched manually to find additional studies.
The search terms were fenugreek (fenugreekOR trigonella)
AND experimental study design (trialOR clinical trialOR interven-
tion), AND testosterone (TestosteroneOR total testosteroneOR
sex hormoneOR libidoOR sperm), AND (resistance training
OR sport) to identify reports of randomized control trials (RCTs) that
reported the effect of fenugreek extract on serum total testosterone
levels in male.
2.2 |Study selection
All studies were identified from database imported to End Note X7,
and duplicate studies were removed. The selected studies were
checkedoutbasedontitleandabstract(MF,RH).Thefulltextof
the remaining papers was screened again by a reviewer. We evalu-
ated the efficacy of fenugreek extract supplementation on total tes-
tosterone levels by comparing the effects of fenugreek extract at
any dosage with placebo or no intervention group. All RCTs publi-
shed in English were conducted on healthy male subjects more than
18 years old. The exclusion criteria included not randomized, not
clinical, and no control group studies; the combination of fenugreek
extract with other complementary therapies; short duration of study
(<4 weeks); and the studies that did not report the required data for
analyzing.
2.3 |Data extraction
Two reviewers (MF and AM) independently extracted the suitable
data by using a standardized data collection including the full name of
the first author, publication date, study design, origin country, number
of participants, mean age, duration of supplementation, interventions,
and outcome characteristics (differences between baseline and final
mean and SD values of serum total testosterone levels). Graphical data
were converted to numerical data using Graph Digitizer 2.26 software
(Wilborn et al., 2010a).
2.4 |Quality assessment
Two reviewers (MF and AM) assessed the quality of the evidences
using the Cochrane risk of bias assessment tool, independently. Seven
items considered random sequence generation, allocation conceal-
ment, blinding of participants and outcome assessment, selective
reporting, and other bias.
2.5 |Statistical analysis
The data analysis was carried out using the STATA 14.0 software
(Stata, College Station, TX, USA). The effect of fenugreek extract sup-
plement on testosterone levels was calculated by the weighted mean
difference (WMD) with associated 95% confidence intervals. If the
mean serum testosterone was not stated in the studies, the mean and
SD of serum testosterone was calculated by following formulas. Mean
(change) = Mean (Final) Mean (baseline),
SD changeðÞ=
ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
SD baselineðÞ2+ SD finalðÞ2ð2×:5×SD baseline ×SD final
pÞ:
The heterogeneity among studies was investigated by χ
2
test.
Fixed effect model was performed when p> .1 and I
2
< 50% and ran-
dom effect model was performed when p<.1orI
2
50% on the con-
trary. Pvalues <.05 with 95% confidence interval were considered
statistically significant for the statistic test.
3|RESULTS
3.1 |Study selection
We identified 29 relevant studies through searching in title and
abstract and checking the references. After removing duplicates,
19 articles were potentially relevant. Four studies were completed but
not published, and the authors did not send the results of their studies
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
Mens Health [ClinicalTrial.gov], and Efficacy of Fenugreek Seed and Les-
pedeza cuneata in TDS; ClinicalTrial.gov). Eleven studies were excluded
based on the study inclusion and exclusion criteria. The remaining four
studies were regarded potentially for the meta-analysis. The results of
search strategy are shown in Figure 1.
2MANSOORI ET AL.
FIGURE 1 Diagram of study
selection
TABLE 1 Characteristics of the studies included
Author
(year) Country Subject
Mean
age
(year)
Number of
participants
(intervention/
control)
Fenugreek type and dose
(Intervention)
Placebo type and
dose (Control)
Duration
(weeks)
Guo (2018) Albany Healthy male
athletes
24.02 12/12 Furosap capsules
250 mg/day
NR 250 mg/day 12
Rao (2016) Australia Healthy male 55.6 47/50 Fenugreek seed extract
600 mg/day
NR 12
Wankhede
et al.
(2016)
India Healthy male 22.04 29/26 glycoside fraction of
fenugreek seeds
2*300 mg/day
di-calcium
phosphate
2*300 mg/day
8
Wilborn
(2010)
USA Resistance-trained
men
21 17/13 Fenugreek capsule
500 mg/day
Maltodextrin
500 mg/day
8
MANSOORI ET AL.3
3.2 |Characteristics of the studies included
We identified a total of 206 participants, 105 individuals on interven-
tion and 101 on placebo, from the four included eligible RCTs. All the
relevant studies that were published from the inception of databases
until November 2018 were assessed. Because of the importance of tes-
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
male. All included studies did not show any harmful side effects of fenu-
greek extract. Details of included studies are shown in Table 1.
3.3 |Effect of fenugreek extract on total
testosterone levels
There was a significant effect of the rise in total testosterone levels in
the fenugreek extract group. In comparison with placebo group, the
mean total testosterone levels in the subjects receiving fenugreek
extract was higher (WMD = 0.85 95% CI [0.10, 1.60]; p= .026;
Figure 2).
There was heterogeneity between the trials (Q= 16.28; df =3;
p= .001; I
2
= 81.6%).
We used random effect to evaluate serum total testosterone
levels due to the significant heterogeneity.
The quality for each trial of the included studies is presented in
Table 2.
4|DISCUSSION
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
leaves, seeds, and roots are used as spice, herb, and vegetable
(Adamska & Lutomski, 1971; Bahmani, Shirzad, Mirhosseini,
Mesripour, & Rafieian-Kopaei, 2016; Yadav & Baquer, 2014). Studies
indicated remedy effect of Fenugreek on hypercholesterolemia and
hyperglycemia in diabetes and prediabetes patients (Gong et al.,
2016). Other results has shown that Fenugreek reduced liver
enzymes, lipid accumulation, and ethanol-induced toxicity in liver
(Al-Wabel, Mousa, Omer, & Abdel-Salam, 2008; Kaviarasan,
FIGURE 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
Reference
Random
sequence
generation
Allocation
concealment
Blinding of
participants
Blinding of
outcome
assessment
Follow-up
>80%
Free of
selective
reporting
Free of
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.
4MANSOORI ET AL.
Ramamurty, Gunasekaran, Varalakshmi, & Anuradha, 2006; Raju &
Bird, 2006). Moreover, fenugreek has vitamins and essential oil; its
seeds contain several glycosides such as phenolic components like
number of kaempfero, apigenin, quercetin glycosides, and flavonoids:
apigenin-7-O-glycoside, luteolin-7-O-glycoside, saponins, and sapoge-
nins (Chatterjee, Variyar, & Sharma, 2009; Kenny, Smyth, Hewage, &
Brunton, 2013; Naidu, Shyamala, Naik, Sulochanamma, & Srinivas,
2011; Shang et al., 1998). Diosgenin and yamogenin are the most
steroidal sapogenins of fenugreek seed extract (Osman, Elhussein, &
Albalawi, 2014). Especially, diosgenin is shown as an important
precursor for synthetizing steroidal hormones such as testosterone
(Rao & Kale, 1992). Wilborn et al. showed that administration of
500 mg commercially of fenugreek seed extract in in college-age men
lead to increased testosterone and decreased dihydrotestosterone
levels via inhibiting aromatase and 5-αreductase activity (the enzymes
that convert testosterone to estradiol and dihydrotestosterone,
respectively; Wilborn et al., 2010a).
Animal and in vitro studies indicated that fenugreek extract
through several mechanisms improves serum testosterone levels.
Glycoside-rich fraction of Trigonella foenum-graecum seed such as
saponins and sapogenins has shown androgenic and anabolic activ-
ity (Wankhede et al., 2016). Protodioscin is a steroidal saponin
phytochemical found in some plant species. Evidences suggested
the efficacy of saponins especially protodioscin-like components
on testosterone and anabolic status (Pavin et al., 2018; Salgado
et al., 2017). In addition, evidences suggested that diosgenin
(a steroidal sapogenin) stimulates sex hormonal pathways(Rao &
Kale, 1992).
The substantial heterogeneity in current study results was partly
explained by small numbers of participants in the studies. Because of
lack of sufficient relevant data, we could not make other subgroup
analysis on the parameters.
5|CONCLUSIONS
To specify the efficacy of fenugreek extract on serum total testoster-
one levels in male, further study will be required to take into consider-
ation different doses and durations and in combination with other
complementary therapies.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
ORCID
Anahita Mansoori https://orcid.org/0000-0003-2935-9589
Seyedahmad Hosseini https://orcid.org/0000-0001-6191-682X
Marzie Zilaee https://orcid.org/0000-0002-9895-8887
Mojdeh Fathi https://orcid.org/0000-0003-4784-0077
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How to cite this article: Mansoori A, Hosseini S, Zilaee M,
Hormoznejad R, Fathi M. Effect of fenugreek extract
supplement on testosterone levels in male: A meta-analysis of
clinical trials. Phytotherapy Research. 2020;16. https://doi.
org/10.1002/ptr.6627
6MANSOORI ET AL.
... Additionally, a systematic review was conducted for assessing fenugreek extract has revealed that it has a substantial impact on serum total testosterone level in men 18 . ...
... Trigonella foenu-graecum has been widely used in folk medicine as an antihypertensive, anti-hypercholesterolemic, improving cardiac function in patients with coronary artery diseases, as hormonal replacement therapy in postmenopausal symptoms, and in male sexual dysfunction (4,11,18). ...
Article
Trigonella foenum-graecum has long been used as a medicinal plant for the treatment of nutritional, metabolic and sexual dysfunction in both genders.Objectives: our study aimed at evaluating the possible effects of different dosage forms of fenugreek seeds on the male reproductive system in animals.Methods: In a randomized controlled study, 40 male albino rats weighing 180 to 260 gm. were equally divided into four groups, one control and the other three groups were treated by the administration of either powder (200 mg/kg), aqueous (500mg/ml) or oily extract (200mg/ml) forms, 3 times weekly for 8 weeks. Serum luteinizing hormone, follicle-stimulating hormone, prolactin, estrogen, progesterone, and testosterone levels were evaluated, as well as histological examination & sperm analysis. Results: Concerning the oily extract dosage form, a highly significant decrease (P< 0.01) in FSH was recorded in comparison to other groups. LH was reduced significantly (P< 0.05) in the three treated comparative groups. However, progesterone and estrogen levels were significantly increased (P<0.05) after the administration of the oily form. Testosterone level was detected higher only in the aqueous form with a significant increase (p< 0.05) in sperm count, unlike the other 2 forms. The results have revealed a significant (p< 0.05) decrease in all sperm evaluated parameters as well as destructions in testicular tissues after the administration of the oily form. Conclusion: The effect of the aqueous form on the male hormonal levels have been significantly noticed with remarkable changes in the sperm vitality as well the sperm count. The oily form showed a devastating action on all the evaluated parameters.
... One of the highest-quality studies on fenugreek is the meta-analysis by Mansoori et al., which included 4 studies performed on healthy volunteers, a total of 105 adults in exposure groups and 101 control subjects. The mean age in these studies ranged from 21 to 55.6 years [48]. The authors concluded that fenugreek affects the level of total testosterone; however, they noted a great heterogeneity of the studies included. ...
... Fenugreek contains a variety of sapogenins such as diosgenin and yamogenin. In particular, diosgenin may be an important precursor in testosterone synthesis [48]. On the other hand, it is suggested that fenugreek can increase testosterone through an aromatase and 5α reductase inhibition [45]. ...
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“Testosterone boosters” (TB)—are supplements that are claimed to increase testosterone levels in the human body. While the consumption of TB may be popular among athletes, there is insufficient evidence both about the safety and the real efficacy of TB. In our review, we searched MEDLINE/PubMed and Cochrane Library for studies on the effects of 15 substances that are claimed to increase testosterone levels Anacyclus pyrethrum; Bulbine natalensis; Epimedium (horny goat weed); L-arginine; L-carnitine; magnesium; Mucuna pruriens; pantothenic acid; selenium; shilajit Eurycoma longifolia (Tongkat Ali); Serenoa repens (saw palmetto); boron; Withania somnifera (ashwagandha); and Trigonella foenum-graecum (fenugreek) in athletes and healthy adults under 55 years of age. We found such studies regarding 10 out of 15 substances: L-arginine (3 studies); L-carnitine (2); magnesium (1); selenium (2); shilajit (1); Tongkat Ali (2); Serenoa repens (1); boron (3); ashwagandha root (2); and fenugreek (7). Many of them fail to prove the efficacy of these substances to increase testosterone levels. Tongkat Ali, ashwagandha, and fenugreek were the substances with the strongest evidence. The positive effect of magnesium and shilajit on testosterone concentration was shown in single studies. Conflicting data found that L-arginine, L-carnitine, Serenoa repens, selenium and boron do not appear to increase testosterone levels. There are almost no data on the safety profile of various TB components; however, certain TB components may be linked to coagulation, and pancreatic and hepatic disorders. Based on the review, the authors conclude that at present TB cannot be recommended for use by athletes due to insufficient data on their efficacy and safety. Lazarev A, Bezuglov E. Testosterone Boosters Intake in Athletes: Current Evidence and Further Directions. Endocrines. 2021; 2(2):109-120. https://doi.org/10.3390/endocrines2020011
... Despite the popularity of fenugreek, most of these abovementioned claims await verification and scientific proof [4]. Some of the studies done on fenugreek report that it has galactagogue [7,8], anti-inflammatory [9,10], antidiabetic [10], anticholesterolemic [11,12], antihypertensive, kidney and liver protective [13], androgenic/anabolic [14], antibacterial, and anticancer [15] properties. All these medicinal uses and properties show how popular and beneficial this herb is in such a broad spectrum of disease conditions. ...
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... In support of the findings of this review, a recent meta-analysis of clinical trials on fenugreek seed extract supplementation reported a significant increase in testosterone concentrations (68). This meta-analysis included 4 studies (42, 58, 63, 64) but did not include 2 of the studies included in this review because it was conducted in late 2018 and excluded studies with a duration <4 wk. ...
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Background: Age-related changes in testosterone levels in older persons and especially in women have not been fully explored. The objective of this study was to describe age-related trajectories of total testosterone (TT), ammonium sulfate precipitation-measured bioavailable testosterone (mBT), and sex hormone-binding glycoprotein (SHBG) in men and women from the Baltimore Longitudinal Study of Aging, with special focus on the oldest adults. Methods: Participants included 788 White men and women aged 30-96 years with excellent representation of old and oldest old, who reported not taking medications known to interfere with testosterone. Longitudinal data were included when available. TT, mBT, and SHBG were assayed. Age-related trajectories of mBT were compared with those obtained using calculated bioavailable testosterone (cBT). Generalized least square models were performed to describe age-related trajectories of TT, mBT, and SHBG in men and women. Results: mBT linearly declines over the life span and even at older ages in both sexes. In men, TT remains quite stable until the age of 70 years and then declines at older ages, whereas in women TT progressively declines in premenopausal years and slightly increases at older ages. Differences in age-related trajectories between total and bioavailable testosterone are only partially explained by age changes in SHBG, whose levels increases at accelerated rates in old persons. Noteworthy, although mBT and cBT highly correlated with one another, mBT is a much stronger correlate of chronological age than cBT. Conclusion: In both men and women, mBT linearly declines over the life span and even at old ages. Its relationship with age-related phenotypes should be further investigated.