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The purpose of this study was to systematically review the scientific literature about the effects of supplementation with Ashwagandha (Withania somnifera) on maximum oxygen consumption (VO2max), as well as to provide directions for clinical practice. A systematic search was conducted in three electronic databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA). The inclusion criteria were: (a) VO2max data, with means ± standard deviation before and after the supplement intervention, (b) the study was randomized controlled trial (RCT), (c) the article was written in English. The quality of evidence was evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A meta-analysis was performed to determine effect sizes. Five studies were selected in the systematic review (162 participants) and four were included in the meta-analysis (142 participants). Results showed a significant enhancement in VO2max in healthy adults and athletes (p = 0.04). The mean difference was 3.00 (95% CI from 0.18 to 5.82) with high heterogeneity. In conclusion, Ashwagandha supplementation might improve the VO2max in athlete and non-athlete people. However, further research is need to confirm this hypothesis since the number of studies is limited and the heterogeneity was high.
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Eects of Ashwagandha (Withania somnifera) on
VO2max: A Systematic Review and Meta-Analysis
Jorge Pérez-Gómez 1, Santos Villafaina 2,* , JoséCarmelo Adsuar 1,
Eugenio Merellano-Navarro 3and Daniel Collado-Mateo 4
1HEME Research Group, Faculty of Sport Sciences, University of Extremadura, 10003 Caceres, Spain; (J.P.-G.); (J.C.A.)
2Physical Activity and Quality of Life Research Group (AFYCAV), Faculty of Sport Science, University of
Extremadura, 10003 Cáceres, Spain
3Facultad de Educación, Universidad Autónoma de Chile, Talca 3460000, Chile;
4Centre for Sport Studies, Rey Juan Carlos University, Fuenlabrada, 28943 Madrid, Spain;
*Correspondence:; Tel.: +34-927-257-460
Received: 15 March 2020; Accepted: 14 April 2020; Published: 17 April 2020
The purpose of this study was to systematically review the scientific literature about the
eects of supplementation with Ashwagandha (Withania somnifera) on maximum oxygen consumption
), as well as to provide directions for clinical practice. A systematic search was conducted
in three electronic databases following the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses Guidelines (PRISMA). The inclusion criteria were: (a) VO
data, with
standard deviation before and after the supplement intervention, (b) the study was
randomized controlled trial (RCT), (c) the article was written in English. The quality of evidence was
evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation
(GRADE) approach. A meta-analysis was performed to determine eect sizes. Five studies were
selected in the systematic review (162 participants) and four were included in the meta-analysis
(142 participants). Results showed a significant enhancement in VO
in healthy adults and
athletes (p=0.04). The mean dierence was 3.00 (95% CI from 0.18 to 5.82) with high heterogeneity.
In conclusion, Ashwagandha supplementation might improve the VO
in athlete and non-athlete
people. However, further research is need to confirm this hypothesis since the number of studies is
limited and the heterogeneity was high.
Keywords: ergogenic aids; maximum oxygen consumption; performance sports; physical fitness
1. Introduction
Maximum oxygen consumption (VO
) is a physiological parameter that defines the aerobic
capacity of a person. It is an indicator of the cardiorespiratory fitness that describes health status [
] and
sport performance [
]. Focusing on competitive sports, the VO
, together with running economy
and the anaerobic threshold, is one of the main factors that determine success in endurance activities [
and also contributes to increase the team sports performance by increasing work intensity, distance
covered, and number of sprints completed [
]. However, from the point of view of the physical training,
there are still controversies about the best training intensity to enhance the VO2max [5,6].
Apart from sport performance, VO
has special interest in the field of health. Low values of
(<17.5 mL
) are associated with an increased risk of mortality and loss of independent
lifestyle in adults and elderly [
], while high values of cardiorespiratory fitness have been associated
with a reduced risk of cardiovascular diseases [
]. The VO
level is also important in children,
where a higher aerobic capacity is related to better quality of life [10].
Nutrients 2020,12, 1119; doi:10.3390/nu12041119
Nutrients 2020,12, 1119 2 of 11
Ashwagandha (Withania somnifera) is a plant in the Solanaceae family. The extract of the
Ashwagandha root has many biological implications due to its diverse phytochemicals [
], so it
has been used, singly or in combination with other natural plants, in many research studies for its
properties: anti-diabetic [
], anti-inflammatory [
], anti-microbial [
], anti-tumor [
], anti-stress [
cardioprotective [
], or neuroprotective [
]. It also displays enhanced endothelial function [
reduces reactive oxygen species [
], regulates apoptosis [
], and modulates mitochondrial
function [
], showing to be eective to treat aging eects [
], anxiety and stress [
], arthritis [
cognitive functions and memory [
], diabetes [
], epilepsy [
], fatigue [
], neurodegenerative
diseases [26], pain [27], thyroid function [28], and skin diseases [29].
In spite of the relevant benefits of supplementation with Ashwagandha, only four meta-analyses
have been carried out evaluating its ecacy on anti-inflammatory eects [
], on impotence and
infertility treatment [
], on neurobehavioral disorders [
] and anxiety [
]. However, there are no
meta-analyses that analyze the eect of Ashwagandha on physical performance. Therefore, the purpose
of this study was to systematically review the scientific literature about the eects of supplementation
with Ashwagandha on VO
and to provide practical recommendations. Besides, a meta-analysis
was carried out to determine the eect sizes of Ashwagandha on VO2max.
2. Methods
The review was conducted following the statements of the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses Guidelines (PRISMA).
2.1. Literature Search
To find the studies reported in the meta-analysis, several electronic databases were screened:
PubMed (Medline), Web of Science (which includes other databases such as Current Contents Connect,
Derwent Innovations Index, Korean Journal Database, Medline, Russian Science Citation Index, and
Scielo Citation Index) and Google Scholar. The search was conducted in September 2019. The search
terms were: (a) the type of treatment (Ashwagandha or “withania somnifera”) and (b) the outcome
variable (“oxygen consumption” or “aerobic” or “VO
”). The search was conducted using the treatment
and the outcome variables, separated by the Boolean operator “and”.
2.2. Study Selection
The inclusion criteria were: (a) VO
data, with means
standard deviation (SD) before and
after the supplement intervention; (b) the study was a randomized controlled trial (RCT); (c) the article
was written in English. Two independent authors selected the potentially eligible articles from the
databases. There were no disagreements.
2.3. Quality of the Evidence and Risk of Bias
The quality of the evidence was categorized using the Grading of Recommendations, Assessment,
Development and Evaluation (GRADE) approach. The risk of bias was assessed by the Cochrane
Collaboration’s tool for assessing risk of bias. This tool classified the selection, performance, detection,
attrition, and reporting bias into low, high, or unclear risk of bias.
2.4. Data Collection
Two authors independently extracted data from the studies. The information included: participants,
interventions, comparisons, outcomes, and study design (PICOS), following the recommendations
from the PRISMA statement. Table 1shows age, sex, sample size, and condition of the participants.
Table 2presents intervention and the comparison groups, including type of supplementation with the
doses, duration of the study, and the daily frequency of the supplementation. Figure 3 displays results
for the dierent outcomes. Study design was not included in any table because all studies were RCT.
Nutrients 2020,12, 1119 3 of 11
Table 1. Characteristics of the sample.
RCT Weeks Groups,
Sample Size and Sex Age (Years) Country Population
Shenoy 2012 8 AS: 20 (M and F)
CG: 20 (M and F) 18–27 India Elite cyclists
Malik 2013 8 AS: 16 (M)
CG: 16 (M) 16–19 India Hockey players
Choudhary 2015 12 AS: 25 (M and F)
CG: 25 (M and F) 20–45 India Athletes
Tripathi 2016 2 AS: 10 (M)
CG: 10 (M) 18–45 India Healthy adults
Sandhu 2010 8 AS: 10 (M and F)
CG: 10 (M and F) 18–25 India Healthy adults
RCT: randomized controlled trial; AS: Ashwagandha group; M: males; F: females; CG: control group.
Table 2. Characteristics of the interventions.
Ashwagandha Group Control Group Dose
of the
Dose (g)
Type of
Type of
Shenoy 2012 Ashwagandha in
gelatin capsules
Capsules containing
starch powder 500 8 weeks twice 56
Malik 2013 Roots of WS
Sugar power was
filled in gelatin
500 8 weeks once 28
One capsule of KSM-66
Identical capsules
containing sucrose 300 12 weeks twice 50.4
Tripathi 2016
WS aqueous extract in
the capsule form Maize starch capsule 330 2 weeks once 4.62
Sandhu 2010 WS filled in gelatin
Capsules filled with
flour 500 8 weeks once 28
RCT: randomized controlled trial; KSM-66: commercial name of an Ashwagandha extract; WS: Withania Somnifera.
Total dose was calculated as: total dose (g) =(dose (mg) ×daily frequency ×study duration (days))/1000.
2.5. Statistical Analysis
The main outcome of this meta-analysis was VO
. The meta-analysis was conducted using
the Revision Manager (RevMan) software (version 5.3) obtained from Cochrane Collaboration web.
Post-intervention mean and SD were extracted and used for meta-analyses. All articles reported VO
max as mL/kg/min. Mean dierence was calculated using a random model. The heterogeneity between
the studies was calculated using Tau
, I
, and Chi
tests. Although there is no consensus about the
definition of “mild”, “moderate”, or “severe” heterogeneity, Higgins and Thompson [
] suggested
that values for I
higher than 56% would mean large heterogeneity while values lower than 31% would
be related to low heterogeneity.
3. Results
3.1. Study Selection
The PRISMA flow diagram is showed in Figure 1. A total of 129 records were identified, 9 of
which were removed because they were duplicated. Of the remaining 120 articles, 92 were excluded
because they were not related with the topic, 4 studies were not written in English, and 4 were reviews.
After reading the remaining 20 articles, another 15 studies did not meet the inclusion criteria and were
excluded. Therefore, 5 studies were included in the systematic review. However, the article by Sandhu
et al. [
] was excluded from meta-analysis due to the odd results. In this regard, they evaluated
healthy young males and females aged between 18 and 25 with body mass index between 18 and 25.
Their mean peak VO
was lower than 14mL/kg/min, which is so much lower than expected for
healthy young people and less than half the mean of the rest of the included studies (46.18 mL/kg/min).
Nutrients 2020,12, 1119 4 of 11
We tried to contact with the authors in order to obtain a reason for that, but at the time this article was
considered for publication, we did not receive a response. Considering that in the article authors did
not explain an incremental test to obtain the VO
, we believe that they measured the gas exchange
at rest, reporting the oxygen consumption (VO
). Therefore, this article was included in systematic
review but not in the meta-analysis.
Figure 1. Flow chart delineating the complete systematic review process.
3.2. Quality of Evidence and Risk of Bias
The evidence of the eects on VO
was initially classified as “high quality” due to all the
selected articles were RCT, but the evidence dropped twice because of the small sample size and due
to the high degree of heterogeneity. Therefore, the final quality of the evidence was low. The Cochrane
Collaboration’s tool for assessing risk of bias (Figure 2) showed that the poorer scores were obtained in
the performance and detection bias due to unclear reporting.
3.3. Study Characteristics
Study characteristics are summarized in Table 1. The total number of participants included in this
systematic review were 162. Of these, 81 belonged to the Ashwagandha group and 81 were the placebo
(control) group. The age ranged from 16 to 45 years old. The sample was comprised exclusively of
healthy adults and athletes.
Nutrients 2020,12, 1119 5 of 11
Figure 2. The Cochrane Collaboration’s tool for assessing risk of bias.
3.4. Interventions
The characteristics of the Ashwagandha supplementation and placebo group are displayed in
Table 2. The doses varied from 300 to 500 mg and the daily frequency intake was once or twice a day.
The total duration of the intervention varied from 2 to 12 weeks.
3.5. Outcome Measures
The study of Choudhary et al. [
] found a significant group*treatment interaction in the VO
The remaining four articles only found within-group improvement in VO
after the supplement
intervention [35,3739].
Regarding meta-analysis results, a significant (p=0.04) mean dierence was observed. Figure 3
showed a mean dierence of 3.00 (95% CI from 0.18 to 5.82). The heterogeneity level was large
according to the I
=84%. The quality of the evidence was low according to the GRADE classification.
Nutrients 2020,12, 1119 6 of 11
Figure 3. Meta-analysis results of the eects of Ashwagandha supplementation on VO2max.
Nutrients 2020,12, 1119 7 of 11
4. Discussion
The purpose of this study was to systematically review the scientific literature about the eects of
supplementation with Ashwagandha on VO
and to carry out a meta-analysis to determine the
overall eect. After 20 articles were assessed for eligibility, 15 articles were excluded since they did not
report VO
2 max
. A total of 5 articles were included in the systematic review [
]. However, one article
was excluded from the meta-analysis [
] since the reported mean VO
was abnormally low for
healthy young people and less than half the mean of the rest of the included studies (46.18 mL/kg/min),
which may indicate that they were not actually reporting VO
but VO
at rest. The results of this
meta-analysis showed that supplementation with Ashwagandha may be useful to improve VO
athletes [
] and healthy adults [
]. Table 2displayed the amount of Ashwagandha used in
each study, which varied from 330 up to 1000 mg/day, which is inside the limits, 750 to 1250 mg/day,
found to be well tolerated and safe [40]. In this regard, none of the five articles reported any relevant
side eect as a consequence of the treatment, achieving a high compliance with the treatment and very
low number of dropouts.
The two studies that achieved the highest treatment eect and eect size [
] were those with
the highest Ashwagandha intake (>50 g in the whole program). Therefore, it seems like the higher the
dose, the higher the improvement in VO
. However, the study by Tripathi, Shrivastava, Ahmad Mir,
Kumar, Govil, Vahedi, and Bisen [
] did not observe any significant dierence between the eects of a
330 mg intake and the eects of a 500 mg intake after 2 weeks. Therefore, further studies comparing
the eect of dierent doses, as well as studies with longer duration are needed.
In general terms, the overall eects were better in those studies with a sample comprised of
athletes [
] compared with the studies with healthy adults [
]. This is interesting since, as
expected, baseline levels were higher in athletes and, consequently, larger improvements were expected
in non-athlete healthy adults. It could be that the eects of supplementation with Ashwagandha might
be linked to the physical activity levels of the participants, promoting and increasing the physiological
adaptations to physical exercise. However, this hypothesis should be explored in future studies.
The VO
defines the body’s ability to transport and utilize oxygen, so this physiological parameter
is associated with endurance performance. Many factors contribute to the VO
values, including
genetic predisposition [
], enzymes [
], muscle fiber type [
], or training [
]. It is also known that
nutritional supplementation can improve the eects of training and reach higher performance [
Previous studies with Ashwagandha administration observed improvement in working capacity test
in rats by increasing the swimming endurance test [
]. As endurance performance is determined
by mitochondrial function, some reasons for the Ashwagandha to improve cardiorespiratory fitness
can be the significant eects observed on mitochondrial and energy levels, by reducing the succinate
dehydrogenase enzyme activity in the mitochondria and benefiting Mg-ATPase activity [
]. Previous
studies showed that Ashwagandha significantly enhanced the hemoglobin concentration and red blood
cells in animals [
] and also in humans [
], with the subsequent increase in the capacity to transport
oxygen to the muscles. Moreover, it should be considered that Ashwagandha has shown to have
anti-fatigue [
] and anti-stress [
] actions. This could be connected to the significant improvement
in the time to exhaustion of the experimental group that could be observed in the study of Shenoy,
Chaskar, Sandhu, and Paadhi [
]. Some of the chemical constituents of Whitania somnifera [
] such as
flavonoids, alkaloids, and steroidal lactones (withanolides) or the antioxidants (superoxide dismutase,
catalase, and glutathione peroxidase) could be behind the improvements of VO
. Therefore, further
studies are needed to explore which are the chemical constituents and mechanism that may explain
the potential improvement in the VO2max.
Although all mechanisms by which Ashwagandha can improve the VO
have not been
described yet and future studies are needed to elucidate that improvement, it is known that
Ashwagandha exhibits little or no associated toxicity [
], so it seems that this Ayurvedic herb
“Ashwagandha” (Withania somnifera) can be safely used for improving cardiovascular fitness in healthy
Nutrients 2020,12, 1119 8 of 11
adults and also in athletes, oering an additional alternative as a nutritional supplement to enhance
Some limitations in the present meta-analysis can be mentioned. The first one is related to the
search strategy, only articles published in English were included and a few databases were used.
Another limitation can be the large heterogeneity in the included articles. Dierent doses, levels of
physical activity, or the inclusion of both women and men in the protocols make it very dicult
to achieve a high level of evidence. In addition, the systematic review and meta-analysis was not
prospectively registered in any public database. Furthermore, in order to have a better understanding
of long-term ergogenic benefit and potential side eects from Ashwagandha root extract, longer
duration studies are needed.
5. Conclusions
Ashwagandha supplementation might improve the VO
in athlete and non-athlete people.
The analyzed studies used oral administration of Ashwagandha which varied between 2 and 12
weeks with intakes between 300 to 1000 mg/day. Due to the limited number of studies included in
this systematic review and meta-analysis, further research is needed to confirm the eects and the
recommended dose.
Author Contributions:
Conceptualization, J.P.-G., J.C.A. and D.C.-M.; methodology, J.P.-G., S.V., E.M.-N. and
D.C.-M.; software, J.C.A., and D.C.-M.; formal analysis, J.P.-G., S.V., J.C.A., E.M.-N., and D.C.-M.; investigation,
J.P.-G., S.V., J.C.A., E.M.-N., and D.C.-M.; data curation, J.P.-G., J.C.A. and S.V.; writing—original draft preparation,
J.P.-G., S.V. and D.C.-M.; writing—review and editing, J.P.-G., S.V., J.C.A., E.M.-N. and D.C.-M.; supervision, J.P.-G.,
S.V., J.C.A., E.M.-N. and D.C.-M. All authors have read and agreed to the published version of the manuscript.
S.V. is supported by a grant from the regional Department of Economy and Infrastructure of the
Government of Extremadura and European Social Fund (PD16008).
Conflicts of Interest: The authors declare no conflict of interest.
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... Clinical trials have demonstrated various effects of ashwagandha, such as improved sleep quality [75][76][77]; improved cognitive performance [78], quality of life, and mental alertness [76] in elderly subjects; decreased HAM-A scores in subjects with anxiety [79,80] and high stress [81]; increased VO 2max in healthy adults and athletes [82,83]; decreased Perceived Stress Scale scores and serum cortisol in stressed adults [78,82,84]; and improved depression and anxiety scores [85] and Perceived Stress Scale scores [86] in individuals with schizophrenia or schizoaffective disorder. Due to its stress-reducing effects, ashwagandha is considered an adaptogen, a substance that helps the body respond and adapt to stress and environmental changes [84]. ...
... Clinical trials have demonstrated various effects of ashwagandha, such as improved sleep quality [75][76][77]; improved cognitive performance [78], quality of life, and mental alertness [76] in elderly subjects; decreased HAM-A scores in subjects with anxiety [79,80] and high stress [81]; increased VO 2max in healthy adults and athletes [82,83]; decreased Perceived Stress Scale scores and serum cortisol in stressed adults [78,82,84]; and improved depression and anxiety scores [85] and Perceived Stress Scale scores [86] in individuals with schizophrenia or schizoaffective disorder. Due to its stress-reducing effects, ashwagandha is considered an adaptogen, a substance that helps the body respond and adapt to stress and environmental changes [84]. ...
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Herbal and dietary supplement (HDS) use has grown exponentially in the United States. Unfortunately, the incidence of HDS-related liver injury has proportionally increased. Despite the potential for certain HDSs to cause clinically significant liver injury, they are not regulated by the Food and Drug Administration. Recent efforts have been made to regulate HDSs but are far removed from the scrutiny of prescription medications. Scant literature exists on HDSs and their risks of causing liver injury. In this comprehensive review, we examine trends of HDS use in the United States and the pathophysiologic mechanisms of drug-induced liver injury (DILI) of certain HDSs. Finally, we review usage rates; benefits, if any; purported pathophysiology of DILI; and propensity for progression to fulminant hepatic failure of nine HDSs linked to clinically significant DILI.
... It is further reported to boost the immune system, increase the production of vital fluids, lymph blood, semen, cells, memory power and possesses immunomodulatory, hemopoietic, rejuvenation and antineoplastic effects [13]. W. somnifera enhances human physical performance, including strength and oxygen use during exercise [14][15][16]. The food supplements comprising extracts of this plant have been shown to increase male fertility by increasing testosterone level, sperm concentration, semen volume, and sperm motility [17,18]. ...
... Although melanin pig- Tousif et al. Process Biochemistry xxx (xxxx) [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] ment protects the mammalian skin from harmful UV radiations, [53] but over production of melanin leads to hyperpigmentation and causes melasma, freckles, age spots, or senile lentigines [54]. Tyrosinase is a copper-containing enzyme that catalyzes melanin synthesis and is held responsible for hyperpigmentation in human skin [55][56][57]. ...
Withania somnifera (L.) Dunal has been identified as a miracle herb, thus the present study was carried out to investigate W. somnifera growing in Cholistan Desert for its secondary metabolic profile and various biological activities. The WS-C fraction of methanolic extract (WS-M) of W. somnifera was found rich in phenolics (39.96±0.90 mg GAE/g extract), and it exhibited significant DPPH (30.69±0.78 mg TE/g extract) and ABTS (113.60±2.41 mg TE/g extract) free radical inhibitory activities, cupric (Cu⁺²) and ferric (Fe⁺³) reducing potential as 157.51±2.10 and 124.60±0.34 mg TE/g extract. The same fraction also exhibited strong total antioxidant capacity (1.39±0.01 mmol TE/g extract) in phosphomolybdenum assay. Other fractions displayed relatively lower potential. In metal-chelating assay, WS-M, WS-E and WS-B showed nearly equal potential with values of 22.35±0.62, 20.96±0.12 and 22.10±0.75 mg EDTAE/g of the extract, while in AChE, BChE and tyrosinase inhibitory assay, again WS-C fraction was most active (7.50±0.21, 8.01±0.53 mg GALAE/g extract and 36.81±0.20 mg KAE/g extract, respectively). In α-amylase and α-glucosidase inhibitory assay, WS-C showed significant potential with values as 0.74±0.01 and 1.14±0.004 mmol ACAE/g extract, respectively. UHPLC-MS analysis of WS-C fraction leads to identify 100 secondary metabolites of phenolic, withanolide, terpenoid, steroid, lignin, flavonoid and limonoid classes of compounds. This profile makes W. somnifera a fascinating plant. These findings were validated by computational studies, which revealed that selected compounds exhibited high binding free energy and inhibition constants with the enzymes tested. Pearson correlation analysis clearly established that the phenols in the tested extracts were the main players as antioxidants and enzyme inhibitors, which was also substantiated through Principal Component Analysis (PCA). These results suggest that chloroform might be suitable for preparing further applications with W. somnifera extracts, and this plant can be placed in the list of top-selling herbs, and may become source of commercial assets.
... Pérez-Gómez et al.(2020) [7] worked on the study entitled "Effects of Ashwagandha (Withania somnifera) on VO 2max : A Systematic Review and Meta-Analysis." During their work, they concluded that its supplementation might improve maximum oxygen consumption (VO 2 max) in athletes and non-athletes[7].Balkrishna et al. (2020) [8] have worked on "Withanone from Withania somnifera may inhibit Novel Coronavirus (COVID-19) Entry by disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor" and based on their study, they concluded that this herb may be helpful in controlling the infection of COVID-19[8].Ng et al. ...
... Pérez-Gómez et al.(2020) [7] worked on the study entitled "Effects of Ashwagandha (Withania somnifera) on VO 2max : A Systematic Review and Meta-Analysis." During their work, they concluded that its supplementation might improve maximum oxygen consumption (VO 2 max) in athletes and non-athletes[7].Balkrishna et al. (2020) [8] have worked on "Withanone from Withania somnifera may inhibit Novel Coronavirus (COVID-19) Entry by disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor" and based on their study, they concluded that this herb may be helpful in controlling the infection of COVID-19[8].Ng et al. ...
In the present pandemic, demands for natural herbs and spices have been surprisingly enhanced, and the reason behind enhancements in the demands of these spices and herbs are genuine because they have super immunity boosting capability, and they strengthen the human body against various diseases and pathogenic microbes. In this direction, Withania somnifera, also popularly known as ‘Ashwagandha,’ is one of the popular herbs known for its different medicinal values and various biological functions. This Ayurvedic herb is known for its potential anti-inflammatory properties, fatigue reduction, stress reduction, anticancer properties, and it is also helpful for diabetic patients, arthritis pain, and others. Due to lack of research and scientific evidence, there is no concrete information on the direct medicinal importance and use of this plant, but it has a historical pharmaceutical role in Ayurveda as traditional Indian medicine, and its medicinal impacts have now been proved via various pieces of research. This chapter concisely describes the various recent clinical aspects and pieces of research on this medicinally valuable herb.
... A systematic review and meta-analysis of four RCTs reported that ASW significantly increased maximum oxygen consumption in healthy adults [97]. Rahman et al. [98] examined the potential for renal toxicity of ASW in albino rats. ...
Introduction Ashwagandha (ASW) is the extract of the plant Withania somnifera. It is widely used in complementary, alternative and integrative medicine (CAIM) but is little discussed in mainstream modern medical literature. Areas covered We performed a review of potential pharmacotherapeutic properties of ASW. Studies were sourced from relevant online and offline databases. In animal models, ASW displays antioxidant activity. It has GABAergic and other neurotransmitter modulatory effects. It reduces apoptosis and promotes synaptic plasticity. It improves cognition and reverses induced cognitive deficits. It attenuates indices of stress. In human subjects, ASW enhances adaptogenesis in healthy adults. It modestly benefits generalized anxiety disorder and obsessive-compulsive disorder, and symptom severity in schizophrenia, substance use disorders, and attention deficit hyperactivity disorder. It improves sleep quality. Expert opinion ASW may confer modest benefit in certain neuropsychiatric conditions. Its benefits may arise from induction of neuroplasticity, antioxidant and anti-inflammatory effects, and modulation of GABA and glutamate as well as other neurotransmitters. The antioxidant and anti-inflammatory actions may also benefit neurodegenerative states. Reports of clinical benefit with ASW must be interpreted with caution, given the paucity of randomized clinical trials (RCTs). Greater methodological rigor is necessary before clinical recommendations on ASW can be confidently made.
... Sandhu et al. conducted a double-blind placebo-controlled study of W. somnifera with various parameters, such as increased power, velocity, VO 2 max, and augmented VO 2 max, and observed a significant reduction in the resting systolic blood pressure [94] In this study, normal healthy subjects received standardized WSREt in the form of capsules with a proper dose for a particular period and were evaluated for cardiovascular protection and cardiorespiratory endurance. Results confirmed that W. somnifera showed a prominent effect as a cardioprotective [95]. ...
... During aerobic exercise, VO2Max is very important to determine and track a person's cardiorespiratory physiological fitness 14,15 .The higher a person's VO2Max, the better the level of cardiorespiratory fitness, so it has the potential to increase performance in the world of sports [16][17][18] . The ability to predict VO2Max with the development of a test instrument based on sensor technology has the potential to provide an opportunity to obtain valuable information about cardiorespiratory fitness more effectively. ...
... Gómez et al. (2020) [7] worked on the study entitled "Effects of Ashwagandha (Withania somnifera) on VO 2max : A Systematic Review and Meta-Analysis." During their work, they concluded that its supplementation might improve maximum oxygen consumption (VO 2 max) in athletes and non-athletes[7].Balkrishna et al. (2020) [8] have worked on "Withanone from Withania somnifera may inhibit Novel Coronavirus (COVID-19) Entry by disrupting Interactions between Viral S-Protein Receptor Binding Domain and Host ACE2 Receptor" and based on their study, they concluded that this herb may be helpful in controlling the infection of COVID-19[8].Ng et al. (2020) presented a systematic review on the clinical use of W. somnifera(Ashwagandha) to ameliorate cognitive dysfunction[9].Khanchandani et al. (2019) ...
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin. Audience: This book is an ideal resource for scholars (in life sciences, phytomedicine and natural product chemistry) and general readers who want to understand the importance of herbs, spices and traditional medicine in pharmaceutical and clinical research.
Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused Coronavirus disease 2019 (COVID-19) and the patients with COVID-19 might be managed with traditional medicine like Ayurveda alone or in combination with standard allopathic treatment as Ayurveda is one of the oldest traditional medicinal systems followed by millions around the globe. Methods The literature was searched in databases such as LitCOVID, Google Scholar, Science Direct, EBSCO, Scopus, Web of science, EMBASE, and reference lists to identify articles relevant to the use of Ayurvedic medicines in the management of COVID-19. Results Several clinical studies have determined the efficacy of Ayurvedic medicines and formulations in the management of patients with COVID-19. Conclusion The Ayurvedic medicines and formulations having antiviral, antioxidant, anti-inflammatory, and immunomodulatory properties could be used along with standard allopathic medicines to assist in the earlier clearance of virus, speedy recovery of patients with COVID-19, faster discharge from hospitals, and the prevention of further deterioration.
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The most recent pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged the health systems around the world. Currently, there is no definite treatment for COVID-19 and researchers are exploring herbal plant species. Withania Somnifera (WS) and its active ingredients may have potential benefits against COVID-19 activity and related cytokine storm. COVID-19 manifestations are not limited to the respiratory system and extend to vital body organs, a syndrome called multiple organ failure. WS also showed protective effects in different organs such as the lung, heart, liver, and kidneys. In this review, we aimed to summarize the pharmacological effects and underlying mechanisms of WS against COVID-19 and related complications. WS showed anti-inflammatory, antioxidant, hepatoprotective, cardioprotective, antifibrotic, anticancer, and immunomodulatory effects, mainly by downregulating NF-κB and related pathways. The Review Article suggested clinical benefits of WS for COVID-19 were investigated by clarifying their underlying mechanisms in this review.
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Introduction Unhealthy lifestyle and inadequate diet could influence the development of future cardiometabolic disease. The main aim of this study was to determine the association between aerobic fitness and cardiometabolic risk factors in adults, whether this relation is depends of adherence to Mediterranean diet (MD). A secondary aim was to study the combined effect of aerobic capacity and adherence to MD on global cardiometabolic risk score (CMRS). Method A total of 79 adults (38% women) enrolled between 18–40 year from Cádiz. We measured adiposity indicators, blood pressure, triglycerides, glucose and inflammatory profile (interleukin-6 and tumor necrosis factor) and was computed (CMRS). Aerobic fitness was measured by maximal oxygen comsuption through an incremental stress test by cycleergometer. The MD patterns was measured using the questionnaire of adherence to MD. The association between aerobic fitness and cardiometabolic risk factors was examined using a lineal regression and it was adjusted for different confounders. CMRS on the lifestyle was analyzed using the ANOVA test, with statistical significance level of p < 0.05 in Bonferroni. Results Linear regression showed inverse association between aerobic fitness and cardiometabolic risk factors (all p ≤ 0.05) in the model without adjustment. Blood pressure and triglycerides lost the association after adjust model for sex, age, and adherence to MD. Participants with high aerobic fitness and high adherence to MD show a lowest CMRS (−1.083 ± 2.325 vs. 2.802 ± 1.759). Conclusions Aerobic fitness was inversely associated with fatness risk factors, that relationship is independent to adherence to MD. A high adherence to MD could modulate blood pressure. A combination of high aerobic capacity and high adherence to MD could reduce the adverse consecuence of a low adherencie to MD.
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Background: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. Methods: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. Results: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). Conclusions: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings.
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Background Accumulating evidence shows that a propensity towards a pro-inflammatory status in the brain plays an important role in schizophrenia. Anti-inflammatory drugs might compensate this propensity. This study provides an update regarding the efficacy of agents with some anti-inflammatory actions for schizophrenia symptoms tested in randomized controlled trials (RCTs). Methods PubMed, Embase, the National Institutes of Health website ( ), and the Cochrane Database of Systematic Reviews were systematically searched for RCTs that investigated clinical outcomes. Results Our search yielded 56 studies that provided information on the efficacy of the following components on symptom severity: aspirin, bexarotene, celecoxib, davunetide, dextromethorphan, estrogens, fatty acids, melatonin, minocycline, N-acetylcysteine (NAC), pioglitazone, piracetam, pregnenolone, statins, varenicline, and withania somnifera extract. The results of aspirin [mean weighted effect size (ES): 0.30; n = 270; 95% CI (CI) 0.06–0.54], estrogens (ES: 0.78; n = 723; CI 0.36–1.19), minocycline (ES: 0.40; n = 946; CI 0.11–0.68), and NAC (ES: 1.00; n = 442; CI 0.60–1.41) were significant in meta-analysis of at least two studies. Subgroup analysis yielded larger positive effects for first-episode psychosis (FEP) or early-phase schizophrenia studies. Bexarotene, celecoxib, davunetide, dextromethorphan, fatty acids, pregnenolone, statins, and varenicline showed no significant effect. Conclusions Some, but not all agents with anti-inflammatory properties showed efficacy. Effective agents were aspirin, estrogens, minocycline, and NAC. We observed greater beneficial results on symptom severity in FEP or early-phase schizophrenia.
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Maximal oxygen uptake (V̇O2max) and muscle mass decreases with age. The loss of cardiorespiratory fitness and muscle strength is accelerated with physical inactivity and has well‐documented consequences for morbidity and all‐cause mortality. Participation in exercise training programs will improve one or more of the cardio‐metabolic risk factors, but the long‐term effect of such programs are questionable. Here we re‐examined 25 old (72 ± 4 yr.) men and women who considered him/her‐self as “success‐full agers” and were participants in a 3‐month alpine skiing training program six years earlier. The program focused on healthy aging and included health questionnaires, measurement of lipids and glycemic parameters in blood and a VO2max test. Thirteen and twelve subjects were in the intervention (IG) and the control group (CG), respectively. In response to the training program, subjects improved their cardio‐metabolic risk factors. However, after six years all positive effects had disappeared. Approximately 80% of the subjects had total cholesterol and LDL cholesterol above and HDL cholesterol below the recommended values, but these subjects remained the most metabolically deteriorated, including an increase in fasting glucose concentrations. We conclude that people seem to follow their individual trajectory in terms of cardio‐metabolic risk factors, and participation in a relatively short lasting exercise training program with emphasis on healthy aging does not change that. Long‐lasting change of lifestyle probably requires a continued attentional focus, goal setting and feedback. This article is protected by copyright. All rights reserved.
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Background: Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti-inflammatory, and immunomodulatory properties. Objective: The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. Methods: To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. Results: Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. Conclusion: From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.
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The present study examined the effects of exercise utilising traditional resistance training (leg press) or 'cardio' exercise (recumbent cycle ergometry) modalities upon acute physiological responses. Nine healthy males underwent a within session randomised crossover design where they completed both the leg press and recumbent cycle ergometer conditions. Conditions were approximately matched for effort and duration (leg press: 4 × 12RM using a 2 s concentric and 3 s eccentric repetition duration controlled with a metronome, thus each set lasted 60 s; recumbent cycle ergometer: 4 × 60 s bouts using a resistance level permitting 80-100 rpm but culminating with being unable to sustain the minimum cadence for the final 5-10 s). Measurements included VO 2 , respiratory exchange ratio (RER), blood lactate, energy expenditure, muscle swelling, and electromyography. Perceived effort was similar between conditions and thus both were well matched with respect to effort. There were no significant effects by 'condition' in any of the physiological responses examined (all p > 0.05). The present study shows that, when both effort and duration are matched, resistance training (leg press) and 'cardio' exercise (recumbent cycle ergometry) may produce largely similar responses in VO 2 , RER, blood lactate, energy expenditure, muscle swelling, and electromyography. It therefore seems reasonable to suggest that both may offer a similar stimulus to produce chronic physiological adaptations in outcomes such as cardiorespiratory fitness, strength, and hypertrophy. Future work should look to both replicate the study conducted here with respect to the same, and additional physiological measures, and rigorously test the comparative efficacy of effort and duration matched exercise of differing modalities with respect to chronic improvements in physiological fitness
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Objective To evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line. Methods After treating HepG2cells with Ashwagandha water extract (ASH-WX; 6.25 mg/ml–100 mg/ml), cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Antioxidant activities (total antioxidant, glutathione S-transferase and glutathione reductase), Fas-ligand level, tumour necrosis factor-α (TNF-α) level and caspase-3, -8, and -9 activities were measured. Molecular modelling assessed the binding-free energies of Ashwagandha in the cyclin D1 receptor. Results The MTT assay demonstrated increased cytotoxicity following treatment of HepG2 cells with ASH-WX compared with control untreated cells and theIC50was 5% (approximately 5.0 mg/ml). Antioxidant activities, Fas-ligand levels and caspase-3, -8 and -9 activities significantly increased, while TNF-α level significantly decreased following ASH-WX treatment compared with control untreated cells. Molecular docking analysis revealed a good prediction of binding between cyclin D1 and Ashwagandha. There was significant accumulation of ASH-WX-treated HepG2cells in the G0/G1 and G2/M phases compared with the control untreated cells. Conclusion Ashwagandha could be a powerful antioxidant and a promising anticancer agent against HCC.
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Temporal Lobe Epilepsy involves a sequence of events which can lead to neurotransmitter signalling alterations. Many herbal extracts are considered as alternative therapeutic method for epilepsy management. In the present study, we investigated the effect of Withania somnifera (WS) root extract and Withanolide A (WA) in the management of Temporal Lobe Epilepsy. Confocal imaging of TOPRO-3 stained cortical sections showed severe damage in epileptic brain. We also observed a reduced antioxidant potential and increased peroxide level in epileptic group. Oxidative stress resulted in the down regulation of CREB, NF-κB and TNF-α with an up regulation of the apoptotic factors Caspase 8, 3 and bax in epileptic group. Epileptic condition also resulted in an increased muscarinic receptor binding and mRNA expression in the cerebral cortex. Withania somnifera and Withanolide A significantly reversed the altered muscarinic receptor expression and reversed the oxidative stress and resultant derailment in cell signalling. Thus our studies suggest that Withania somnifera and Withanolide A play an important role in central muscarinic receptor functional balance and activation of antioxidant system in the cerebral cortex of temporal lobe epileptic condition. These findings can be of immense therapeutic significance for epileptic management.
Despite the recent successes of targeted cancer immuno-therapies, drug resistance and disease relapse remain a huge burden in cancer patient treatment. This has fueled renewed interest in natural product discovery to identify new pharmacophores for innovative cancer drug development. Reverse pharmacology approaches of Withania somnifera leaves and roots (alternatively also called Ashwagandha or Indian ginseng in traditional Ayurvedic and Unani folk medicine) have identified Withaferin A (WA) as the most bioactive compound for treatment of inflammatory ailments, supporting traditional use of their corresponding extracts in indigenous medicine. In this review we summarize preclinical in vivo evidence for therapeutic cancer applications of WA and provide a biochemical framework of its polypharmaceutical effects against cancer hallmarks.
Ethnopharmacological relevance: Diabetes and hypertension are pathophysiologically related diseases that co-exist with a wider complex of metabolic diseases having similar set of risk factors. There are numerous ethnopharmacological evidences on the anti-diabetic and/or anti-hypertensive properties of medicinal plants from various parts of the world, which are used as therapies to concomitantly manage diabetes and hypertension. Aim of the review: This article reviewed findings on medicinal plants with both anti-diabetic and anti-hypertensive effects reported in same experimental study to facilitate the development of dual-acting therapies against diabetes and hypertension. Materials and methods: A literature search was carried out on different scientific search engines including, but not limited to “PubMed”, “Google Scholar”, “Scopus” and ScienceDirect to identify published data in which plants in same experimental studies were reported to possess both anti-hyperglycemic and anti-hypertensive effects. Subsequently, the anti-diabetic/anti-hypertensive potency ratio (ψ) of the medicinal plants was computed. Results: Sixty-four studies with 102 plant species matched the selection criteria. Members of the Fabaceae family were the most investigated plants, while the ψ greatly varied across the plants, with only 11 plants having a ψ ≃ 1. Withania somnifera Dunal was the only plant reported to show blood glucose-lowering and diuretic effects in humans, comparable to daonil. Caffeic acid, chlorogenic acid, caftaric acid, cichoric acid, verbascoside, leucosceptoside A, isoacteoside, fucoxanthin and nicotinamide were the reported dual acting anti-diabetic and anti-hypertensive compounds identified and/or isolated in the plants. Conclusions: This review suggests that medicinal plants possess varied therapeutic dynamics against hypertension and diabetes that could be exploited for the discovery of therapeutic preparation(s) or agent(s) for treating the two diseases.