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Maca (Lepidium meyenii Walp.)
on semen quality parameters: A
systematic review and
meta-analysis
Hye Won Lee
1
, Myeong Soo Lee
2
*, Fan Qu
3
, Je-Won Lee
4
and
Eunseop Kim
5
1
KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea,
2
KM
Science Research Division, Korea Institute of Oriental Medicine, Daejeon, South Korea,
3
Women’s
Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China,
4
BM Internal Korean
Medicine Clinic, Daegu, South Korea,
5
You and Green Korean Medicine Clinic, Daejeon, South Korea
Background: This study aimed to examine the evidence for the effect of
Lepidium meyenii Walp. [Brassicaceae] (L. meyenii W.), known as maca, on
improving semen quality.
Methods: Nine databases were searched for randomized controlled trials
(RCTs) that examined the parameters for improvements in semen quality,
regardless of the type of L. meyenii W. The risk of bias (ROB) among the
studies was evaluated according to the Cochrane ROB tool.
Results: Five RCTs met all of the inclusion criteria. Three RCTs showed mixed
efficacy of maca in improving semen quality parameters, including sperm
concentration and sperm motility, in men experiencing infertility. The meta-
analysis also failed to show the efficacy of maca in increasing the sperm
concentration compared to the placebo (weighted mean difference, 2.22,
95% confidence interval −2.94 to 7.37, p= 0.4). Two other RCTs also
showed mixed effects of maca on several semen quality parameters in
healthy men.
Conclusion: The evidence from the included studies suggests unclear effects of
maca on semen quality parameters in both men experiencing infertility and
healthy men. However, the total number of RCTs and the total sample size were
too small to draw firm conclusions.
KEYWORDS
maca, Lepidium meyenii W., semen, infertility, herbal medicine
OPEN ACCESS
EDITED BY
Yue Liu,
Cardiovascular Diseases Center, Xiyuan
Hospital, China
REVIEWED BY
Francesca Ciani,
University of Naples Federico II, Italy
Mehran Rahimlou,
Zanjan University of Medical
Sciences, Iran
*CORRESPONDENCE
Myeong Soo Lee,
drmslee@gmail.com
SPECIALTY SECTION
This article was submitted to
Ethnopharmacology,
a section of the journal
Frontiers in Pharmacology
RECEIVED 03 May 2022
ACCEPTED 03 August 2022
PUBLISHED 30 August 2022
CITATION
Lee HW, Lee MS, Qu F, Lee J-W and
Kim E (2022), Maca (Lepidium meyenii
Walp.) on semen quality parameters: A
systematic review and meta-analysis.
Front. Pharmacol. 13:934740.
doi: 10.3389/fphar.2022.934740
COPYRIGHT
© 2022 Lee, Lee, Qu, Lee and Kim. This
is an open-access article distributed
under the terms of the Creative
Commons Attribution License (CC BY).
The use, distribution or reproduction in
other forums is permitted, provided the
original author(s) and the copyright
owner(s) are credited and that the
original publication in this journal is
cited, in accordance with accepted
academic practice. No use, distribution
or reproduction is permitted which does
not comply with these terms.
Abbreviation: CAM, complementary and alternative medicine; CIs, confidence intervals; CONSORT,
CONsolidated Standards Of Reporting Trials; L. meyenii,Lepidium meyenii; RCT, randomized
controlled trial; ROB, risk of bias; WMD, weighted mean difference.
Frontiers in Pharmacology frontiersin.org01
TYPE Systematic Review
PUBLISHED 30 August 2022
DOI 10.3389/fphar.2022.934740
1 Introduction
Male-specific elements are one of the primary underlying
causes of infertility (Sharlip et al., 2002). In this context, semen
analysis is a key indicator of challenges that lead to this ailment
(Fields et al., 2013). Couples frequently explore complementary
and alternative medicine (CAM) to resolve their fertility issues
(Bardaweel, 2014;FatemehGhaedi et al., 2020;Choi et al., 2021;
Sönmez et al., 2021). According to a recent study, approximately
one-fourth of infertile couples seek assistance with at least one
form of CAM (Sönmez et al., 2021), particularly herbal products.
Another study showed that over 70% of participants used CAM
products, among which herbal medicines were the most
commonly used (Bardaweel, 2014). One review provides
evidence suggesting the efficacy of herbal medicine as a
treatment for infertility (Lee et al., 2021).
Between 1,300 and 2,000 years ago, the Andean population
appreciated the maca (Lepidium meyenii Walp [Brassicaceae]) plant
for its nutritional and therapeutic properties and its positive effect on
male and female reproductive functions, sexual functions,
osteoporosis, depression, anxiety, and energy (Tafuri et al., 2019).
One such popular herbal medicine that is used to improve semen
quality and treat infertility in general is the maca plant, and most of
the experimental data in the literature mainly report the effects of the
red, yellow and black hypocotyl types (Gonzales et al., 2004;
Gonzales et al., 2006a). Notably, this plant from Peru has long
been utilized to enhance sexual functions (Shin et al., 2010;Lee et al.,
2011). According to numerous in vivo studies, maca is replete with
spermatogenic features, which, in turn, positively affect sexual
behavior and sperm parameters (Gonzales et al., 2001;Gonzales
et al., 2004;Chung et al., 2005;Bogani et al., 2006;Lentz et al., 2006;
Rubio et al., 2006;Clémentetal.,2010;Clement et al., 2012). One
systematic review of the effects of maca on improving semen quality
has been published (Lee et al., 2016), and the review includes three
randomized controlled trials (RCTs) and 2 uncontrolled clinical
trials with several types of controls used for comparisons. This
review suggested that maca may be beneficial for improving semen
quality. However, this review is now outdated.
Therefore, this article aimed to critically assess the evidence
from RCTs on the efficacy of maca to improve semen quality.
2 Methods
This protocol is registered at reviewregistry1335 (Lee et al.,
2022).
2.1 Search of databases
The following databases were searched from inception to
April 2022: The Cochrane Central Register of Controlled Trials,
EMBASE, PubMed, Virtual Health Library, AMED, KoreaMed,
Korean Studies Information, Research Information Service
System, and China National Knowledge Infrastructure
(CNKI). The strategy related to the search comprised a
combination of thesaurus terms and free text. The search
terms included “maca OR Lepidium”AND “hyposperm OR
sperm OR subfertility”. The details of the search strategies for
the DBs were given in Supplementary Material. A manual search
was conducted of all retrieved articles to ensure their relevance.
The search strategy was devoid of any restrictions on language.
2.2 Criteria for considering studies
2.2.1 Study design and participants
RCTs that included both infertile and healthy men were
included.
2.2.2 Types of interventions and controls
Trials assessing the effects of all maca preparation types,
irrespective of their origins, and trials using only maca as the
mode of treatment compared to any type of control were
included. However, trials that compared varied maca types
and any trials with maca as a part of a complex intervention
were excluded from the study. Additionally, placebo-controlled
trials were included.
2.2.3 Type of outcome measures
Sperm motility and sperm concentration were the primary
outcomes. The secondary outcomes were sperm morphology,
volume, and counts.
2.3 Data extraction and risk-of-bias
assessment
The full texts of hard copies of all articles were read. Data were
extracted by two independent reviewers according to preset criteria
that included methods (comprising the study design, blinding, and
follow-up duration), samples (e.g., disease duration, age, size,
conditions, and size of population), control treatment,
intervention and outcome measures. In addition, the Cochrane
risk-of-bias tool was implemented to examine the quality of the
included trials (Higgins et al., 2011). Disagreements among
reviewers, if any, were resolved through discussion. We assessed
the ROB of the included studies, regardless of the publication status.
For unpublished reports and abstracts, we used available
information or contacted the original authors.
2.4 Synthesis of data
Cochrane Collaboration software Review Manager (v.5.4.1) for
Windows was used to conduct statistical assessments. An
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assessment of categorical data was conducted by calculating risk
ratios to examine clinical efficacy. Additionally, the mean difference
(MD) was calculated to assess continuous data. Continuous and
categorical variables were articulated as values of efficacy with 95%
confidence intervals (CIs). For instances of varied scales for outcome
variables, a decision was made to use the standardized MD over
weighted MD (WMD). When heterogeneity (p<0.1 according to
thechi-squaretestandHigginsI
2
≥50%) was observed, we
performed subgroup analyses to ascertain the factor underlying
the clinical heterogeneity. Publication bias was assessed using the
Egger regression method and by constructing funnel plots. In cases
of missing data, incomplete or missing information was sought from
the authors of the main study. Albatross plots were also created
using STATA/SE v.16.1 (StataCorp LLC, College Station, TX,
United States) to visualize the effects of direction on primary and
secondary outcomes.
3 Results
3.1 Study description
In our search, 352 articles were identified, and five of these
met the criteria for inclusion (Kim, 2011;Poveda et al., 2013;
Melnikovova et al., 2015;Alcalde and Rabasa, 2020;Melnikovova
et al., 2021)(Figure 1;Table 1). Among these, one RCT each was
conducted in Spain (Alcalde and Rabasa, 2020), Korea (Kim,
2011), and Panama (Poveda et al., 2013), and two RCTs were
conducted in the Czech Republic (Melnikovova et al., 2015;
Melnikovova et al., 2021). Across all five studies, maca (1–5g)
was administered orally to the participants. The treatment
duration ranged from twelve to 16 weeks. In two studies, the
male participants were healthy (Kim, 2011;Melnikovova et al.,
2015), while the participants in other studies had problems
FIGURE 1
Study flow chart. A flowchart of the patient selection process.
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Lee et al. 10.3389/fphar.2022.934740
related to fertility (Poveda et al., 2013;Alcalde and Rabasa, 2020;
Melnikovova et al., 2021). Table 2 shows the composition,
concentration, use, source, and quality control of maca in the
included studies.
3.2 Risk of bias
Three RCTs reported random sequence generation methods
and employed allocation concealment (Melnikovova et al., 2015;
Alcalde and Rabasa, 2020;Melnikovova et al., 2021)(Figure 2). The
double-blind design was used in all five studies, but the baseline
between the three groups was significantly different (Melnikovova
et al., 2015;Alcalde and Rabasa, 2020;Melnikovova et al., 2021).
Notably, one RCT was published in the form of an abstract, and
mostofthedomainswereunclear(Poveda et al., 2013). Additionally,
the other RCT was a report that remained unpublished, and the
majority of domains were unclear (Kim, 2011).
3.3 Effects of interventions
3.3.1 Men with infertility
Among the three aforementioned studies (Poveda et al., 2013;
Alcalde and Rabasa, 2020;Melnikovova et al., 2021), one RCT
indicated that maca exerted a positive effect on the sperm
concentration, but the other two studies did not report a
similar outcome (Poveda et al., 2013;Melnikovova et al.,
2021). The meta-analysis also failed to show the efficacy of
maca in increasing the sperm concentration compared to the
TABLE 1 Summary of the characteristics of the included studies.
First author
(year)
location
Design
Sample
size/
condition
age
(years)
Intervention
(regimen)
Control intervention
(regimen)
Main outcome
measures
Results
Melnikovova
(2015) Czech
20 healthy men (A) L. meyenii Walp. (1.75 g/d,
for 12 weeks, n= 11)
(B) Placebo (milled apple
fiber, n=7)
1) Sperm
concentration
1) MD, −12.48 [−23.13, −1.83], p=
0.02 in favor of B
2) Total sperm count 2) MD, −22.97 [−102.79, 56.85], NS
3) Progressively
motile sperm count
3) MD, −9.51 [−18.76, −0.26], p=
0.04 in favor of B
4) Motile sperm
count
4) MD, −8.55 [−18.35, 1.25], NS
5) Normal sperm
morphology
5) MD, 5.15 [1.13, 7.17], p= 0.007 in
favor of A
6) Semen volume 6) MD, 0.55 [0.04, 1.06], p= 0.03 in
favor of A
Kim (2010) Korea 45 healthy men
30–60
(A) L. meyenii Walp. (5 g/d,
for 12 weeks, n= 15)
(C) Placebo (5 pills/d, n = 15) Motile sperm count A + B vs. C, p<0.05 in favor of A + B
(B) Fermented maca (5 g/d for
12 weeks, n= 15)
A vs. C, NS; B vs. C, p= 0.03 in favor
of B
Poveda (2013)
Panama
60 infertile
men NR
(A) L. meyenii Walp. (1 g/12 h,
n=15)
(B) Placebo tablets (1 pill/
12 h, n = 15)
1) Sperm
concentration
1) NS
(C) L-Carnitine (1 pill/12 h,
n = 15)
2) Sperm motility 2) p<0.05 in favor of A
(D) Spermotrend (1 pill/8 h,
n = 15)
3) Sperm morphology 3) NS
Melnikovova
(2021) Czech
50 infertile men
28–52
(A) L. meyenii Walp. (2.8 g/d,
for 16 weeks, n= 25)
(B) Placebo (milled apple
fiber + sucrose, n= 25)
1) Sperm
concentration
1) MD, -0.38 [-2.35, 1.59], NS
2) Total sperm count 2) MD, -11.81 [-19.02, -4.60], p=
0.001 in favor of B
Alcalde (2020)
Spain
69 infertile men
20–40
(A) L. meyenii Walp. (2 g/d for
12 weeks, n= 33)
(B) Placebo (same color and
capsule, n=32)
1) Sperm
concentration
1) MD, 4.88 [2.60, 7.16], p<0.0001 in
favor of A
2) Sperm motility 2) MD, -0.33 [-2.07, 1.41], NS
3) Sperm morphology 3) MD, 0.85 [-0.17, 1.87], NS
4) Semen volume 4) MD, 0.05 [-0.20, 0.30], NS
MD: mean difference; NA: not available; NR: not reported; NS: not significant. The italicized parts were not considered in the analysis. Maca; L. meyenii Walp. [Brassicaceae].
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placebo (WMD, 2.22, 95% CI -2.94 to 7.37, p= 0.4, I
2
= 91%,
Figure 3). The effects of maca on sperm motility were evaluated
in two RCTs. One study showed favorable effects of maca, but the
other one did not. Regarding sperm morphology, no major
difference was observed between the placebo and the herb.
3.3.2 Healthy men
The effect of maca on semen quality in healthy men was
assessed in two RCTs and compared to a placebo (Kim, 2011;
Melnikovova et al., 2015). One RCT did not report any positive
effects of the herb on either sperm concentration or motile/total
sperm count (Melnikovova et al., 2015). The other study
suggested a mixed effect of maca on sperm motility (Kim, 2011).
3.3.3 Adverse events
One RCT listed the reason for withdrawal due to adverse
events (Melnikovova et al., 2021). However, no trial tried to
examine the adverse effects of maca.
3.4 Albatross plot
The albatross plot showing the effects of direction and size
range by pvalue and a particular sample size was generated for
each included study (Figure 4, different outcome groups are
shown in different colors). The points for the subjective data were
scattered across the contour lines (Figure 4). All points were on
the side of a positive association, indicating that maca exerts a
positive effect on semen quality parameters.
4 Discussion
4.1 Summary of findings
Few trials examining the effects of maca on semen quality
parameters have been conducted. The majority of trials that have
been conducted have yet to reveal any positive effect of the herb
on the aforementioned issue. Three of the five trials suggested
that the efficacy of maca in improving semen quality parameters
in infertile men was mixed (Poveda et al., 2013;Alcalde and
Rabasa, 2020;Melnikovova et al., 2021). The same findings were
evident even among healthy men in two other RCTs (Kim, 2011;
Melnikovova et al., 2015)[19,20]. Overall, the evidence indicates
the ambiguous effect of maca on semen quality parameters
among both healthy and infertile men.
One of the five RCTs assessed in the systematic review was
published as an abstract (Poveda et al., 2013), while another
TABLE 2 Compositions, concentration, usage, source, and quality control of maca.
First
author
(year)
Name of
preparation
Concentration Source Quality
control
Chemical
analysis
Components
Melnikovova
(2015)
Gelatinized yellow
maca (L. meyenii
Walp.)
1.75 g/d Peruvian company
Andean Roots, Ltd.
(harvested in the
Peruvian Andes)
Hospital
Preparation
HPLC-DAD
analytical
system
Macamides (methoxy-n-benzyl-
(9Z.12Z.15Z)-octadecatrienamide,
n-benzyl-(9Z.12Z.15Z)-
octadecatrienamide, methoxy-n-benzyl-
(9Z.12Z)-octadecadienamide, n-benzyl-
(9Z.12Z)-octadecadienamide,
n-benzylhexadecanamide, and n-benzyl-
(9Z)-octadecanamide)
Kim (2010) Gelatinized yellow
maca (L. meyenii
Walp.)
5 g/d Cabex S.A. Prepared according
to the Ministry of
Food and Drug
Safety
HPLC-DAD
analytical
system
n-benzyl-hexadecanamide
Poveda (2013) Maca (L. meyenii
Walp.) extracts
1 g/12 h Nature’sWay
Product, Inc
NR NR NR
Melnikovova
(2021)
Gelatinized yellow
maca (L. meyenii
Walp.)
2.8 g/d Peruvian company
Andean Roots, Ltd
Hospital
Preparation
HPLC-DAD
analytical
system
Macamides (unknown macamide, linolenic
acid, n-benzyl-(9Z, 12Z, 15Z)-
octadecatrienamide, linoleic acid,
n-benzyl-(9Z, 12Z)-octadecadienamide,
n-benzylpentadecanamide, n-(3-
methoxybenzyl)-hexadecanamide,
n-benzylhexadecanamide, n-benzyl-(9Z)-
octadecenamide,
n-benzylheptadecanamide,
n-benzyloctadecanamide, methoxy-
derivatives)
Alcalde (2020) Gelatinized maca
(L. meyenii Walp.)
2 g/d NR NR NR NR
HPLC-DAD, high-performance liquid chromatography with a diode-array detection; NR, not reported.
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Lee et al. 10.3389/fphar.2022.934740
one was an unpublished report (Kim, 2011), and both studies
had not undergone peer review. Both studies were also lacking
in details of reporting. We contacted the authors and
interviewed them but were unable to retrieve the full
reports. One RCT was related to a commercial company,
and hidden conflicts of interest regarding their results may
be present (Kim, 2011). In three RCTs, significant differences
in the baseline values of some semen parameters were
reported (Melnikovova et al., 2015;Alcalde and Rabasa,
2020;Melnikovova et al., 2021).
4.2 Differences from previous reviews
The aim of our review was to furtherincreasetheexistingbodyof
evidence by adding new RCTs of maca for improving semen quality.
FIGURE 2
(A) Risk-of-bias graph and (B) risk-of-bias summary: the present authors’judgments about the risk of bias for each item in all included studies.
FIGURE 3
Forest plot of the effect of maca on the semen concentration.
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Unlike prior studies, this study was able to identify two novel RCTs
with low bias-related risks (Alcalde and Rabasa, 2020;Melnikovova
et al., 2021), thus updating the evidence. The results of our review are
slightly different from one previous review showing that maca may be
beneficial for improving semen quality.
4.3 Experimental evidence from in vivo
and in vitro studies
Possible mechanisms of action might assume significance
based on the assumption that maca helped improve semen
quality parameters. Maca products, such as raw materials and
their extracts, have frequently been investigated in sperm
production models and have produced beneficial effects in
preclinical studies. According to multiple studies involving
rodents and horses, among other models, maca intake affected
the reproductive health of males, especially in terms of
spermatogenesis disorders and quantitative sperm
parameters.
Quantitative sperm parameters refer to the analysis of the
sperm volume, concentration, total count, motility, and strict
morphology, regardless of whether abnormalities are present in
the sperm. Several experimental studies have investigated the
potential effects of maca on increasing sperm production. Semen
samples collected from stallions during breeding that were
treated with yellow maca food supplementation indicated a
positive effect on the following parameters: ejaculate volumes,
sperm concentration, total and progressive motility, acrosome
integrity, elongation of the spermatozoa head, and the percentage
of spermatozoa with fragmented DNA (Tafuri et al., 2019;
D’Anza et al., 2021;Del Prete et al., 2018). Several studies of
rodent models found that maca and its extracts improved the
acrosome reaction, sperm motility, and count through the
increased structural and functional preservation of Leydig
cells, which produce testosterone (Valdivia Cuya et al., 2016;
Onaolapo et al., 2018;Aoki et al., 2019). The potential benefits of
maca are related to its androgen-like effects on counteracting
CYP-induced changes in the male reproductive system
(Onaolapo et al., 2018).
Spermatogenesis describes the development of haploid
spermatozoa from germ cells in the seminiferous tubules of
the testes (Ray et al., 2014). According to one study, the oral
administration of maca to rodent models increased spermiation
stages (VII-VIII), germ cell mitosis (IX-XI), the epididymal
sperm count, and daily sperm production (Gonzales et al.,
FIGURE 4
Albatross plot of the main outcomes.
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Lee et al. 10.3389/fphar.2022.934740
2013). In particular, black maca is proposed to be more helpful in
terms of increasing epididymal sperm motility (stages II-VI and
VIII) and total sperm count, while the duration of stage VIII was
reported to increase after the administration of red and yellow
maca (Gonzales et al., 2006a;Gonzales et al., 2006b). Maca
increased the length of stages VII-VIII in the seminiferous
tubules; on the other hand, the cauda epididymal sperm
count, sperm motility, and serum estradiol level were not
affected by any of the doses studied (Chung et al., 2005). The
progression of spermatogenesis in those who received maca had a
longer duration of stages IX-XI for sperm epithelium, and the
duration of stages XII-XIV, which are related to sperm
epithelium, were also increased (Gonzales et al., 2003).
4.4 The gap between clinical and
experimental results
The results of animal studies revealed positive effects of maca
on semen quality, but our review obtained limited evidence for
the effectiveness of maca in infertility. This difference is because
humans and rodent models are fundamentally different in body
structure and metabolism. Although many factors are controlled
in animal studies, they are conducted without fully considering
important aspects of disease development, such as diet, lifestyle,
environmental factors, stress, and psychological/social factors.
Even if the genes of an animal are similar to that of a human, its
physiological functions may differ due to differences in base
sequence, amino acid and protein structure, and responses to
drug metabolism may also be different in humans.
4.5 Limitations
This study is not free from some limitations. For example,
although our extensive searches included Korean/Chinese/
English databases, the selection of all relevant articles cannot
be guaranteed. In particular, manufacturers of maca supported
several studies, which may have resulted in inherent bias. Most
industry-sponsored studies yielded positive results. Each of the
studies included in this review obtained the powder from a
company associated with a particular maca product. In
addition, standardization of herbal medicines, including
maca, is a limited process because the composition of the
phytocomplex depends on several factors, such as cultivation
methods, environmental and weather conditions, place of
cultivation, ecotype considered, preparation methods and
preservation of the herbal supplement. In addition, the
included studies used different treatment doses and courses.
These differences would lead to large heterogeneity, and the
results should be interpreted with caution. The lack of primary
data and their less than optimal quality were other limitations
of this study.
One might wonder why the data from only two studies
should be pooled. The main reasons for performing meta-
analyses are to increase power, improve precision, answer
questions that were not answered by individual studies,
resolve controversies due to conflicting results, and develop
new hypotheses (Deeks et al., 2019). A meta-analysis can be
performed by combining 2 or more studies. However, the use of
statistics does not guarantee that the results are valid. Therefore,
in our case, the conclusions must remain tentative.
One argument for including a publication presented as only
an abstract and an unpublished report is that obtaining and
including data from unpublished studies seems to be an obvious
method to avoid publication bias, but including data from
unpublished studies may itself lead to bias (Sterne et al.,
2008). Another issue is the willingness of researchers of
unpublished studies to provide data (Sterne et al., 2008). We
tried to obtain complete information by contacting, interviewing
or calling the investigators (Kim, 2011). However, we were
unable to obtain this information. In the case of the
unpublished study, we called the investigators and KFDA to
obtain the full report but did not receive the results. We also met
with the CEO of the company manufacturing this product, but he
was unwilling to provide us with full reports. This lack of
information may reduce the strength of the conclusions of
this study.
4.6 Implications for future research
In the future, more stringent methods and standards of
testing must be incorporated to better understand how maca
affects the parameters of semen quality. Factors such as sample
size, standardization of product, and optimal dosage of
treatment, among others, must be considered thoroughly.
CONSORT guidelines must be followed during the process of
conducting clinical trials in future studies.
5 Conclusion
The current systematic review did not provide overwhelming
evidence for the efficacy of maca in improving the parameters of
semen quality in both infertile and healthy men. Nevertheless, a
better informed conclusion can be drawn only after increasing the
sample size, improving the methodological quality of the primary
studies, and conducting more rigorous RCTs in the future.
Data-availability statement
The original contributions presented in the study are
included in the article/Supplementary Material, further
inquiries can be directed to the corresponding author.
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Lee et al. 10.3389/fphar.2022.934740
Author contributions
Conceptualization: HWL, MSL. Data curation: FQ,
J-WL Formal analysis: HWL, MSL, EK. Investigation:
HWL,FQ.Methodology:HWL,MSL.Project
administration:HWL.Resources:J-WL,FQ.Software:
HWL. Supervision: MSL. Writing—original draft: HWL,
MSL. Writing—review and editing: FQ, J-WL, EK. All
authors have read and agreed to the published version of
the manuscript. All authors read and approved the final
version of the manuscript.
Funding
HWL and MSL were supported by the Korea Institute
of Oriental Medicine, Korea (KSN2022240). The funder
had no role in the study design, data collection and
analysis, decision to publish, or preparation of the
manuscript.
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Publisher’s note
All claims expressed in this article are solely those of the
authors and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.
Supplementary material
The Supplementary Material for this article can be found
online at: https://www.frontiersin.org/articles/10.3389/fphar.
2022.934740/full#supplementary-material
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