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

Authors:

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
REFERENCES
Adamska, M., & Lutomski, J. (1971). CFlavonoidglykoside In Den Samen
Von Trigonella foenumgraecum.Planta Medica,20(05), 224229.
Al-Wabel, N., Mousa, H., Omer, O., & Abdel-Salam, A. (2008). Biological
evaluation of aqueous herbal extracts and stirred yoghurt filtrate mix-
ture against alloxan-induced oxidative stress and diabetes in rats. Inter-
national Journal of Pharmacology,4, 135139.
Aswar, U., Bodhankar, S. L., Mohan, V., & Thakurdesai, P. A. (2010). Effect
of furostanol glycosides from Trigonella foenum-graecum on the repro-
ductive system of male albino rats. Phytotherapy Research,24(10),
14821488. https://doi.org/10.1002/ptr.3129
Aydogan, U., Eroglu, A., Akbulut, H., Yildiz, Y., Gok, D. E., Sonmez, A., . . .
Saglam, K. (2012). Evaluation of the isokinetic muscle strength, balance
and anaerobic performance in patients with young male hypogonadism.
Endocrine Journal,59(4), 321327.
Bahmani, M., Shirzad, H., Mirhosseini, M., Mesripour, A., & Rafieian-
Kopaei, M. (2016). A review on ethnobotanical and therapeutic uses of
fenugreek (Trigonella foenum-graceum L). Journal of evidence-based
complementary & alternative medicine,21(1), 5362.
Basualto-Alarcón, C., Jorquera, G., Altamirano, F., Jaimovich, E., &
Estrada, M. (2013). Testosterone signals through mTOR and androgen
receptor to induce muscle hypertrophy. Medicine and Science in Sports
and Exercise,45(9), 17121720.
Chatterjee, S., Variyar, P. S., & Sharma, A. (2009). Stability of lipid constitu-
ents in radiation processed fenugreek seeds and turmeric: Role of phe-
nolic antioxidants. Journal of Agricultural and Food Chemistry,57(19),
92269233.
Dandona, P., & Rosenberg, M. (2010). A practical guide to male hyp-
ogonadism in the primary care setting. International Journal of Clinical
Practice,64(6), 682696.
Fabbri, E., An, Y., Gonzalez-Freire, M., Zoli, M., Maggio, M.,
Studenski, S. A., . . . Ferrucci, L. (2016). Bioavailable testosterone line-
arly declines over a wide age spectrum in men and women from the
Baltimore Longitudinal Study of Aging. Journals of Gerontology Series A:
Biomedical Sciences and Medical Sciences, 71(9), 12021209.
Gong, J., Fang, K., Dong, H., Wang, D., Hu, M., & Lu, F. (2016). Effect of
fenugreek on hyperglycaemia and hyperlipidemia in diabetes and pre-
diabetes: A meta-analysis. Journal of Ethnopharmacology,194,
260268. https://doi.org/10.1016/j.jep.2016.08.003
Hamden, K., Jaouadi, B., Carreau, S., Aouidet, A., El-Fazaa, S., Gharbi, N., &
Elfeki, A. (2010). Potential protective effect on key steroidogenesis
and metabolic enzymes and sperm abnormalities by fenugreek steroids
in testis and epididymis of surviving diabetic rats. Archives of Physiol-
ogy and Biochemistry,116(3), 146155. https://doi.org/10.3109/
13813455.2010.486405
Heufelder, A. E., Saad, F., Bunck, M. C., & Gooren, L. (2009). Fifty-two
week treatment with diet and exercise plus transdermal testosterone
reverses the metabolic syndrome and improves glycemic control in
men with newly diagnosed type 2 diabetes and subnormal plasma tes-
tosterone. Journal of Andrology,30(6), 726733.
Kaufman, J. M., & Vermeulen, A. (2005). The decline of androgen levels in
elderly men and its clinical and therapeutic implications. Endocrine
Reviews,26(6), 833876.
Kaviarasan, S., Ramamurty, N., Gunasekaran, P., Varalakshmi, E., &
Anuradha, C. V. (2006). Fenugreek (Trigonella foenum graecum) seed
extract prevents ethanol-induced toxicity and apoptosis in Chang liver
cells. Alcohol and Alcoholism,41(3), 267273.
Kenny, O., Smyth, T., Hewage, C., & Brunton, N. (2013). Antioxidant prop-
erties and quantitative UPLC-MS analysis of phenolic compounds
from extracts of fenugreek (Trigonella foenum-graecum) seeds and bit-
ter melon (Momordica charantia) fruit. Food Chemistry,141(4),
42954302.
Naidu, M. M., Shyamala, B., Naik, J. P., Sulochanamma, G., & Srinivas, P.
(2011). Chemical composition and antioxidant activity of the husk and
endosperm of fenugreek seeds. LWT-Food Science and technology,44
(2), 451456.
Nguyen, S. M., Ko Ko, N., Sattar, A. S., Gucuk Ipek, E., & Ali, S. (2017).
Pulmonary embolism secondary to testosterone-enhancing herbal
MANSOORI ET AL.5
supplement use. Cureus,9(8), e1545. https://doi.org/10.7759/cureus.
1545
Osman, N. A., Elhussein, S. A., & Albalawi, M. A. D. (2014). Variability in
the content of 25α-and 25β-steroidal sapogenins among thirty mor-
phologically different Sudanese seed accessions of fenugreek. Journal
of Life Sciences,8(9), 744757.
Pavin, N. F., Izaguirry, A. P., Soares, M. B., Spiazzi, C. C., Mendez, A. S. L.,
Leivas, F. G., . . . Cibin, F. W. S. (2018). Tribulus terrestris protects
against male reproductive damage induced by cyclophosphamide in
mice. Oxidative Medicine and Cellular Longevity, 2018, 5758191. doi:
https://doi.org/10.1155/2018/5758191, 9
Qing, X. R., Wan, C. C., Shang, X. J., Li, H. G., Xiong, C. L., Zhan, X. X., . . .
Zong, S. Y. (2017). Relative contributions of testosterone deficiency
and metabolism syndrome at the risk of reduced quality of life: A
cross-sectional study among Chinese mid-aged and elderly men.
Andrologia, 49(9). doi:https://doi.org/10.1111/and.12736
Raju, J., & Bird, R. (2006). Alleviation of hepatic steatosis accompanied by
modulation of plasma and liver TNF-αlevels by Trigonella foenum
graecum (fenugreek) seeds in Zucker obese (fa/fa) rats. International
Journal of Obesity,30(8), 12981307.
Rao, A., & Kale, R. (1992). Diosgenin--a growth stimulator of mammary
gland of ovariectomized mouse. Indian Journal of Experimental Biology,
30(5), 367370.
Salgado, R. M., Marques-Silva, M. H., Goncalves, E., Mathias, A. C.,
Aguiar, J. G., & Wolff, P. (2017). Effect of oral administration of
Tribulus terrestris extract on semen quality and body fat index of infer-
tile men. Andrologia,49(5). https://doi.org/10.1111/and.12655
Shang, M., Cai, S., Han, J., Li, J., Zhao, Y., Zheng, J., . . . Fan, W. (1998).
Studies on flavonoids from Fenugreek (Trigonella foenumgraecum L.).
Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi= China journal of
Chinese materia medica, 23(10), 614616, 639.
Wang, C., Swerdloff, R. S., Iranmanesh, A., Dobs, A., Snyder, P. J.,
Cunningham, G., . . . Berman the Testosterone Gel Study Group, N.
(2000). Transdermal testosterone gel improves sexual function, mood,
muscle strength, and body composition parameters in hypogonadal
men. The Journal of Clinical Endocrinology & Metabolism, 85(8),
28392853.
Wankhede, S., Mohan, V., & Thakurdesai, P. (2016). Beneficial effects of
fenugreek glycoside supplementation in male subjects during resis-
tance training: A randomized controlled pilot study. Journal of Sport
and Health Science,5(2), 176182.
Wilborn, C., Taylor, L., Poole, C., Foster, C., Willoughby, D., & Kreider, R.
(2010a). Effects of a purported aromatase and 5 α-reductase inhibitor
on hormone profiles in college-age men. International Journal of Sport
Nutrition and Exercise Metabolism,20(6), 457465. https://doi.org/10.
1123/ijsnem.20.6.457
Wilborn, C., Taylor, L., Poole, C., Foster, C., Willoughby, D., & Kreider, R.
(2010b). Effects of a purported aromatase and 5alpha-reductase inhib-
itor on hormone profiles in college-age men. International Journal of
Sport Nutrition and Exercise Metabolism,20(6), 457465.
Wu, F. C., Tajar, A., Beynon, J. M., Pye, S. R., Silman, A. J., Finn, J. D., . . .
Forti, G. (2010). Identification of late-onset hypogonadism in middle-
aged and elderly men. New England Journal of Medicine, 363(2),
123135.
Yadav, U. C., & Baquer, N. Z. (2014). Pharmacological effects of Trigonella
foenum-graecum L. in health and disease. Pharmaceutical Biology,52(2),
243254.
Zitzmann, M., Faber, S., & Nieschlag, E. (2006). Association of specific
symptoms and metabolic risks with serum testosterone in older men.
The Journal of Clinical Endocrinology & Metabolism,91(11), 43354343.
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.
... Testosterone is the main sex hormone in men responsible for the development of male sexual characteristics and anabolic function in men. 1 Testosterone plays a crucial role in adult male health including reproductive health, 2,3,4 sexual function, 2 stimulation of Sertoli cell function and spermato-genesis, 5 reduction in pain, 3 well-being,3 cardiovascular function, 3,4 bone density and health, 2,4,5 erythropoiesis, 5 fat metabolism, 2,3 cognitive function, 4,5 metabolic activity, 4 lean body mass, 4 muscle growth, 2,3,5 and strength. 1,2 With nearly 12 million men in the United States suffering from erectile dysfunction, many turn to ways to increase testosterone levels as they age. ...
... Testosterone is the main sex hormone in men responsible for the development of male sexual characteristics and anabolic function in men. 1 Testosterone plays a crucial role in adult male health including reproductive health, 2,3,4 sexual function, 2 stimulation of Sertoli cell function and spermato-genesis, 5 reduction in pain, 3 well-being,3 cardiovascular function, 3,4 bone density and health, 2,4,5 erythropoiesis, 5 fat metabolism, 2,3 cognitive function, 4,5 metabolic activity, 4 lean body mass, 4 muscle growth, 2,3,5 and strength. 1,2 With nearly 12 million men in the United States suffering from erectile dysfunction, many turn to ways to increase testosterone levels as they age. 6 Leydig cells of the testes are responsible for synthesizing nearly 95% of serum testosterone levels in males and are under the influence of the luteinizing hormone secreted by the pituitary gland. ...
... Estimates suggest that by 2050, nearly 87 million Americans will suffer from male hypogonadism. both sexual and nonsexual symptoms: decreased sexual desire, 1,2,7,9,10,13,15,16 erectile dysfunction, 1,2,7,9,13,15 infertility, 13 decreased spontaneous and nocturnal erections, 2,7,13 reduced testicular size, 2,7,13 gynecomastia, 2,7,9,13 loss of body hair including pubic hair and facial hair, 2,7,9,10,13 reduced bone mass, 1,2,7,9,13,28 fatigue, 1,2,7,9,10,15 weakness, 9,16 reduced physical performance, 7,16 depression, 2 anxiety, 9 decreased mood, 1,2,7,16 impaired memory, 7,16 hot flashes, 2 anemia, 2,7,9 decreased lean body mass, 1,2,7,9,10 reduced strength, 2,16 and increased body fat. 1,2,7,9,16 Making the diagnosis of hypogonadism can be challenging for providers. ...
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Methods An initial review of the literature published in the last ten years was performed using the databases PubMed and GoogleScholar with search terms including "Testosterone and Ashwagandha" or "Testosterone and Withania som-nifera", "Testosterone and DHEA", Testosterone and Fenugreek", etc. Results Studies have demonstrated the potential benefits of using herbal and nutritional supplements such as Ashwagandha (Withania somnifera), Fenugreek (Trigonella foenum-grae-cum), Tongkat Ali (Eurycoma longifolia Jack), Zinc, and Vitamin D to increase levels of testosterone in men. Conclusions The use of herbal and nutritional supplementation to increase testosterone levels in men with suboptimal levels have shown benefits to both increasing free and total testos-terone levels, but also show added value in improving semen and sperm parameters such as increased sperm concentration, sperm and semen volume, sperm count, sperm motility, and morning erections, with added benefits in reducing body fat, improving strength and muscle mass, improved mood, and decreasing cortisol levels.
... [17] In terms of toxicity, S. xanthocarpum is generally considered safe for human use at therapeutic doses. [18] The alcoholic fruit-extract of the plant has shown no cytotoxic effect on primary chondrocytes at concentrations ranging from 25 to 500 μg/mL. [16] During in-vivo acute oral toxicity assessment of the fruit extract, no mortality was reported at doses up to 2000 mg/kg in mice. ...
... The FRAP assay measures the reduction of the Fe 3 + / ferricyanide complex to the Fe 2 + /ferrous form in the presence of antioxidants within the extract, [18] was depicted in Figure 1a. The extract's reducing ability showed a significant increase with higher concentrations (10-1000 μg/mL), consistent with the observations made by Jalali Ghassam et al. (2014). ...
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Solanum xanthocarpum, a perennial herb native to India, contains steroidal glycoalkaloids with notable anticancer properties. This study investigated the antioxidant and antiproliferative effects of methanolic fruit extract of S. xanthocarpum on human breast cancer cells (MDA-MB-231). Phytochemical screening and LC-HRMS analysis confirmed presence of various primary and secondary metabolites. Antioxidant activity was assessed through DPPH, ABTS radical scavenging, reducing power, and phosphomolybdate assays. The extract demonstrated significant antioxidant potential with EC50 values of 60.10 ± 0.88 µg/mL (DPPH) and 392.29 ± 3.93 µg/mL (ABTS). Cytotoxicity against MDA-MB-231 cells was evaluated via morphological analysis, MTT assays, and IC50 determination (24.19 ± 0.56 µg/L). Apoptosis was confirmed using dual staining techniques (AO/EB, Hoechst 33342/PI, DAPI), revealing condensed nuclei, apoptotic bodies, and reduced mitochondrial membrane potential, as indicated by Rhodamine staining. Additionally, increased reactive oxygen species (ROS) levels were observed using H2-DCF-DA staining. The total phenolic and flavonoid contents of the extract were 127.78 ± 3.547 mg GAE/g and 98.06 ± 4.289 mg QE/g, respectively. These findings suggest that the methanolic fruit extract of S. xanthocarpum possesses strong antioxidant and anticancer activities, indicating its potential role in cancer treatment. Further studies are warranted to explore its bioactive compounds for developing novel anticancer therapies.
... Five out of six intervention groups show a positive trend for the effect of FEN. These observations are confirmed by previous reviews [50]. However, similar to the meta-analysis considered here, the authors found a large heterogeneity of the included studies [50]. ...
... These observations are confirmed by previous reviews [50]. However, similar to the meta-analysis considered here, the authors found a large heterogeneity of the included studies [50]. Two of the included studies show a moderate effect for FEN [39,41]). ...
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The use of plant steroids to improve physical health and performance is becoming increasingly popular. One of these plant steroids is diosgenin, which is mainly available in fenugreek. As a result, some studies have been conducted to improve physical health. Fenugreek extracts are also becoming increasingly popular in the context of athletic performance. Based on these assumptions, a systematic review with meta-analysis was conducted to evaluate the promoting effects of fenugreek on strength performance, body composition, and hormone concentration. Four databases were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The current version of ReviewManager (RevMan) was used for the statistical evaluation. Seven studies with 449 participants (378 male, 71 female) met the inclusion criteria. A small effect of fenugreek was detected for total testosterone (standard mean difference (SMD): 0.32; 95% confidence interval (CI): 0.09 0.55), free testosterone (SMD: 0.24; 95% CI: −0.04, 0.52), lean body mass (SMD: 0.19; 95% CI: −0.10, 0.49), fat mass (SMD: −0.19; 95% CI: −0.44, 0.05), and leg press performance (SMD: 0.22; 95% CI: −0.02, 0.47), in male athletes. The meta-analysis shows that chronic application of fenugreek has performance-enhancing and anabolic effects in male athletes, but no statements can be made for female athletes.
... improved cognitive functions and Parkinson's symptoms and showed antianxiety, antidepressant, and neuroprotective properties [15,16]. A recent study has reported the beneficial effects of fenugreek and its extract on hormonal-related statuses, such as galactagogue in lactating women and male impotence [17]. ...
... Further, previous studies reported that fenugreek improved cognitive functions and Parkinson's symptoms and showed antianxiety, antidepressant, and neuroprotective properties [15,16]. A recent study has reported the beneficial effects of fenugreek and its extract on hormonal-related statuses, such as galactagogue in lactating women and male impotence [17]. ...
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Fenugreek extracts possess promising physiological and pharmacological properties in human and animal models. This review aims to provide a scientific and comprehensive analysis of the literature on the effects of fenugreek extracts on muscle performance. An extensive online search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. The main medical and scientific engines were searched for articles from May 1981 to May 2021 to capture all scientific studies focused on the effect of fenugreek on muscle and exercise or sport. Out of 81 studies acquired, six eligible randomized controlled trials (RCTs) were included in the qualitative analysis. Four RCTs observed that fenugreek supplementation had significantly improved muscle strength, repetitions to failure (muscle endurance), submaximal performance index, lean body mass, and reduced body fat. Among the remaining two trials, one reported the significant effect of fenugreek extracts on the rate of muscle glycogen resynthesis during post-exercise recovery; however, the other failed to do so. Those two trials were weak, with a minimal sample size (<10). Further, fenugreek glycoside supplementation with sapogenins and saponins reported substantial anabolic and androgenic activity, influencing testosterone levels and muscle performance. It was useful during eight weeks of resistance training without any clinical side effects. Fenugreek with creatine supplementation improved creatine uptake without the necessity of high carbohydrate intake. Hence, fenugreek extracts can be a helpful natural supplement and ergogenic aid for athletes. However, it is better to be aware of doping and liver and kidney damage before using the fenugreek supplement.
... The general chemical structures of steroidal saponins and triterpene saponins are shown in Fig. 7. [3] In particular, diosgenin may be an important precursor for testosterone synthesis. [106] Additionally, steroidal saponins from fenugreek has been suggested to increase testosterone levels through aromatase and 5α reductase inhibition. [107] Fenugreek is considered one of the most effective TB components. ...
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Testosterone boosters (TB) are multi-ingredient dietary supplements that have gained popularity among athletes and the general population. However, certain ingredients in TB are associated with adverse events. The aim of the present study was to analyze dietary TB supplements available for sale online on shop.bodybuilding.com and amazon.com in ten distribution area markets. We evaluated the top five best-selling TB and the most frequently used ingredients of 50 selected TB and the evidence for their efficacy and safety, as well as legislation, statements in the European Union (EU) and sports organizations such as International Olympic Committee (IOC), International Society of Sports Nutrition (ISSN), Australian Institute of Sport (AIS) and World Anti- Doping Agency (WADA). Among 50 TB, 361 components and 98 ingredients were identified. The following ingredients were included in the final review: fenugreek, D- aspartic acid (DAA), 3,3′-diindolylmethane (DIM) or indole-3-carbinol (I3C), Eurycoma longifolia, Cordyceps spp., and ecdysteroids. In EU an authorized health claims refer to few ingredients in TB, mainly minerals, vitamins. Some ingredients were recognized by international sports organizations such as the ISSN, AIS, and WADA and some were identified as unauthorized ingredients/novel food in the EU. Selected ingredients can possibly increase the risk of endocrine system dysregulation.
... Another RCT found that 5 ml/day of Nigella sativa seed oil, a phytonutrientrich food, increased sperm concentration (16.7 million/ ml), normal morphology (9.6%), and motility (6.3%) [265]. The literature on testosterone is more limited; nevertheless, a meta-analysis of four RCTs reported that fenugreek extract supplements increased TT, indicating that glycoside phytochemicals may modulate testosterone levels [266]. These studies show links between certain phytonutrients and MRH, while observational research points to dietary phytonutrient intake possibly playing a significant role in male infertility. ...
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Over the twentieth century, male reproductive health has suffered a substantial decline, as evidenced by decreases in sperm counts and testosterone levels and increases in reproductive pathologies. At the same time, the prevalence of chronic diseases such as obesity, diabetes, and metabolic syndrome has risen dramatically. Metabolic and reproductive health are highly interconnected, suggesting that their respective trends are intertwined and, given the timeframe of such trends, environmental and not genetic factors are most likely to be the primary causes. Industrialization, which began in Europe in the mid-eighteenth century, has resulted in profound changes to our diet, lifestyle, and environment, many of which are causal factors in the rise in chronic diseases. Industrialization results in a nutrition transition from an agricultural unprocessed to a modern processed diet, incorporating increases in sugar, vegetable oils, ultra-processed foods, linoleic acid, trans-fats, and total energy. This dietary shift has incurred numerous adverse effects on metabolic and reproductive health, characterized by chronic inflammation, oxidative stress, and insulin resistance. Moreover, these effects appear to multiply across subsequent generations via epigenetic inheritance. Men’s fertility is markedly affected by obesity and diabetes, with an increase in total energy via processed food intake arguably being the key factor driving the diabesity pandemic. In contrast, wholefoods rich in micronutrients and phytonutrients support male fertility and a healthy body weight. Therefore, men wanting to maximize their fertility should consider making positive dietary changes, such as replacing processed foods with unprocessed foods that support metabolic and reproductive health.
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Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w / w ). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 β -HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.
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Decreased testosterone levels in men are often a normal sign of aging. Testosterone replacement therapy (TRT) is a well-established option for those with symptomatic hypogonadism related to low testosterone levels. Conversely, designer herbal supplements in the context of testosterone supplementation are poorly studied, yet remain popular among aging men who seek the well-known, often enhancing, effects of testosterone that involve muscle mass and sexual function/drive. In 2014, the Food and Drug Administration (FDA) issued a warning about the significant risk of venous clots secondary to testosterone product use. Testosterone-induced polycythemia is one of the proposed mechanisms for this increased clotting propensity. Increased thromboxane A2 receptor density on platelets and increased platelet aggregation have also been linked to testosterone treatment in men. Fenugreek extract is a common active ingredient in commercially available herbal supplements that are often marketed as testosterone enhancers. It is thought that certain fenugreek compounds inhibit aromatase and 5-alpha-reductase activity, leading to diminished testosterone breakdown. However, the efficacy and safety profile of this agent in its use for boosting testosterone levels are unclear. In this case report, we present a patient with new-onset, bilateral pulmonary embolism possibly associated with the daily use of fenugreek-containing testosterone supplements.
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Fenugreek with the scientific name of Trigonella foenum-graceum L and with leaves consisting of 3 small obovate to oblong leaflets is an annual herbaceous plant of the Fabaceae family. It is native to the eastern Mediterranean but is cultivated worldwide. This plant has medicinal alkaloids, steroid compounds, and sapogenins and many uses have been mentioned for this plant in traditional medicine. This plant has been used to ease childbirth, to aid digestion, and as a general tonic to improve metabolism. Trigonelline is considered as the most important metabolite of fenugreek, which is very effective in treating diabetes and decreasing blood cholesterol. Diaszhenin is another important compound in seeds of this plant, which is used in producing medicinal steroids like contraceptive pills. Many studies have been performed on the therapeutic effects and identification of chemical compounds of this plant. In this article, the most important biological effects and reported compounds about fenugreek seed are re...
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Purpose: To evaluate the efficacy and safety of the glycoside fraction of fenugreek (Trigonella foenum-graecum) seeds (Fenu-FG) on physiological parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design. Methods: Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG (1 capsule of 300 mg, twice per day) or the matching placebo at a 1:1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment (baseline) and at the end of the treatment (8 weeks). The efficacy outcome included serum testosterone (total and free) levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity (serum creatinine and blood urea nitrogen), and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed. Results: Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplementation was found to be safe and well-tolerated. Conclusion: Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.
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Ethnopharmacological relevance: Fenugreek is a widely used herb for the treatment of diabetes mellitus (DM) but the effects in randomized controlled trials (RCTs) were controversial. Therefore, a meta-analysis was conducted to estimate the overall effects of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes. Materials and methods: PubMed, EMBASE, web of science, Chinese Biomedical Literature database (CBM), the Cochrane library, China Doctor Dissertations Full-text Database (CDFD), Wan Fang medical database, China Proceedings of Conference Full-text Database (CPCD), China national knowledge internet (CNKI) and China Master's Theses Full-text Database (CMFD) were searched to find the available literatures. RCTs with regard to the efficacy and safety of fenugreek on prediabetes or DM were included. The data of fasting blood glucose (FBG), postprandial 2h blood glucose (2hBG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and high density lipoprotein cholesterol (HDL-c) were extracted to appraise the net change with fixed or randomized effect model. Results: A total of 10 articles (12 studies) were included in the analysis. Pooled results showed fenugreek significantly decreased the levels of FBG (MD -0.84mmol/L; 95% CI -1.38 to -0.31; p=0.002), 2hBG (MD -1.30mmol/L; 95% CI -1.78 to -0.83; p < 0.0001), HbA1c (MD -1.16; 95% CI -1.23 to -1.09; p < 0.00001) and TC (MD -0.30mmol/L; 95% CI-0.56 to -0.03; p=0.03). In spite of the reductive trends in the TG or LDL-c levels and incremental trends of HDL-c, these results were not statistically significant or need further verification for fenugreek in the treatment of DM and prediabetes. Some studies were of low quality. No liver and kidney toxicity were found in all included studies, and the main side effects were gastrointestinal discomfort. Conclusions: The results suggest fenugreek has the hypoglycaemic and TC-lowering efficacy; however, the effects on TG, LDL-c and HDL-c need further confirmations.
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Male fertility can be evaluated through complete semen analysis. Plants belonging to the Tribulus genus are known for their role in enhancing sex hormone levels and semen quality. The aim of this study was to evaluate the effects of T. terrestris on semen quality and physiological parameters. Sixty-five men with abnormal semen evaluation were included in this study, in which they were prescribed with oral administration of Androsten(®) (250 mg of Tribulus terrestris dried extract per capsule). Body fat percentage, lean muscle mass gain, fluctuation in steroid hormone levels and all semen parameters were analysed during the period of treatment. The results demonstrated that decrease in the percentage of body fat and increase in lean mass were significant, as well as increase in dihydrotestosterone levels. Complete semen analysis evaluated at the end of treatment showed significant enhancement in sperm concentration, motility and liquefaction time. Protodioscin, the main phytochemical agent of the Tribulus genus, acts on sertoli cells, germ cell proliferation and growth of seminiferous tubules. This component is known to convert testosterone into dihydrotestosterone, which plays important roles in male attributes. Our results indicate the therapeutic use of Tribulus terrestris by men presenting altered semen parameters, and/or undergoing infertility treatment.
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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.