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Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers

Authors:
International Journal of Complementary & Alternative Medicine
Effects of an Adaptogen-Based Supplement on Stress
Parameters in Healthy Volunteers
Submit Manuscript | http://medcraveonline.com
Introduction
According to the American Institute of Stress, over 70 %
of people regularly experience physical and/or psychological
symptoms caused by stress. The primary causes of stress
in decreasing order of occurrence are: job pressure, money,
health, relationships, poor nutrition, media overload, and sleep
deprivation [1]. Persistent stress leads to fatigue, irritability,
insomnia, weakened immune system, and increased susceptibility
various diseases including cardiovascular diseases. Annual cost to
employers associated with missed work and stress-related health
care in the USA is estimated to be over three billion dollars [1].
       
in cardiovascular disease is well known [2]. Biomarkers of
       
for cardiovascular disease [3], although there is not a single
biomarker that can estimate absolute risk of future events.
Biomarkers exist for assessing oxidative stress, antioxidant levels,
    
chemokines [3].
Oral nutrition in the form of dietary supplements is consumed
by70 % of the general population on a daily basis, including the
use of supplements for the management of stress. Studies indicate
that approximately 70-90 % of health care professionals including
physicians and nurses recommend dietary supplements [4,5],
while 64-69% of the general population use dietary supplements
[6].

increase tolerance to stressors, enhance attention and mental
endurance, increase tolerance to mental fatigue and physical
exhaustion, and reduce stress-induced disorders related to the
immune and neuro-endocrine systems [7-9]. Examples of plants
that have been studied for their anti-stress activities include
Rhodiola, Schizandra, Eleutherococcus, Withania, Emblica and
Glycyrrhiza [7,9-13].
Historically, the term “adaptogen” was introduced into the
   
       
resistance”. For detailed historical reviews see Panossian and
       
used for their adaptogenic properties vary widely, combinations
of plant extracts are commonly used in the preparation of
adaptogenic products [9,14,15]. The purpose of this study was to
evaluate the effects of an adaptogen/vitamin-based supplement
on stress perception and stress indicators in healthy volunteers
after 28 days of supplementation vs. placebo.
Volume 10 Issue 1 - 2017
1Faculty of Pharmacy, Jordan University of Science and
Technology, Jordan
2Creighton University Medical Center, USA
*Corresponding author: Mohd Shara, Department of
Clinical Pharmacy, Chair, King Abdullah University Hospital
and Clinics, Jordan University of Science and Technology, P.O.
Box 3030, Iribd 22110, Tel: Cell: 962-79-753-7770;
Email:
Received:| Published: December 12,
2017
Research Article
Int J Complement Alt Med 2017, 10(1): 00321
Abstract
The effects of an adaptogen-based dietary supplement on stress indicators and
stress perception were evaluated in health volunteers using a double-bind,
placebo-controlled protocol. Seventy-seven healthy 24-60 year old male and
female participants were enrolled, with 74 completing the study. Participants
were given a 28-day supply of the supplement or the corresponding placebo and
instructed to take 1 oz each morning 30 min. before breakfast. The supplement
was a proprietary blend of 10 adaptogens including Eleurtherococcus,
Schizandra and Rhodiola extracts, plus B vitamins. On the morning of enrollment,
the participants completed a stress perception survey, had blood samples drawn
for a highly sensitive C-reactive protein (HS-CRP), cortisol and homocysteine,
and returned to the clinic after 28 days to repeat the stress perception survey
and blood tests. A 40% reduction (p <0.05) in the number of participants with
abnormally elevated HS-CRP in the supplement group compared to the placebo
group was observed. Furthermore, there was a 30% reduction in levels of HS-
CRP in the supplemented group relative to the placebo group. Only one of the 5
subjects (20%) with abnormal (elevated) serum homocysteine levels remained
elevated after 4 weeks of supplementation. In contrast, 4 of the 6 (66%) subjects
in the control group remained elevated after 4 weeks. Five stress perception
parameters were significantly reduced (10-20%) in the supplemented group
compared to two parameters in the placebo group. The results of this study
indicate that the adaptogen/vitamin blend is effective at reducing subjective
(perception survey) and objective (HS-CRP) stress measures compared to the
placebo.
Keywords: Adaptogens; Stress; C-reactive protein; Homocysteine; B vitamins
Citation: Shara M, Kakish E, Stohs SJ (2017) Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers. Int J Complement
Alt Med 10(1): 00321. DOI: 10.15406/ijcam.2017.10.00321
Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers 2/5
Copyright:
©2017 Shara et al.
Materials and Methods
The study was double-blinded and placebo-controlled. A total
of 77 healthy 24-60 year old male and female participants were
enrolled of which 74 completed the study. The protocol was
approved by the Creighton University Institutional Review Board,
       
advertisements in the local paper and on the Creighton University
campus.
The supplement consisted of a liquid formula composed of B
vitamins, betaine, and a proprietary water/ethanol extract blend
derived from 10 adaptogenic plants including Eleutherococcus
sensicosus, Schizandra chinensis, Rhodiola rosea, Glycyrrhiza
uralensis, Crataegus oxyacantha and Aralia manchurica (AdvoCare
International, Plano, TX). A one ounce serving of the extract
contained 2 grams of the extract standardized for its total
polyphenolic content. The composition of the formulation is
presented in Table 1. The placebo contained the same appearance,
        
adaptogen blend.
Table 1:
Amount
Per Serving % DV
Calories 15
Total Carbohydrates 3g 1 %
Sugars 3g
 3.4mg 200%
 40mg 200%
Vitamin B6 (as pyridoxine HCl) 4mg 200%
Folic acid 800mcg 200%
Vitamin B12 (as cyanocobalamin) 500mcg 8333%
Pantothenic acid (as calcium pantothenate) 20mg 200%
Betaine 100mg
Proprietary blend of Eleutherococcus
senticosus
(leaf, stem, root), Schisandra chinensis
(seed),

oxyacantha
(leaf), Viburnum sargenti (leaf, berry),
Glycyrrhiza
uralensis (root), Rhaponticum
carthamoides (root),

(whole
plant), Iconotus obliquus (root)


acid, glycerin, potassium sorbate (as
preservative), sodium benzoate (as
preservative), xanthan gum, and sucralose.
2g
All participants completed a stress perception survey (Table
2) on the morning of enrollment and blood samples were drawn
for highly sensitive C-reactive protein (HS-CRP), cortisol and
homocysteine. The analyses of these biomarkers were conducted
      
       
groups, and were given a 28-day supply of the supplement labeled
either A or B, and instructed to take one ounce of the product each
morning 30 min before breakfast. After 28 days, the participants
completed the same survey and provided blood samples for the
same three analytical tests.
Table 2: Stress level survey.
1 Things must be perfect 1 2 3 4 5
2 I must do it myself 1 2 3 4 5
3 I feel more isolated from my family or close friends 1 2 3 4 5
4 I feel that people should listen better 1 2 3 4 5
5 I am not where I want to be in life 1 2 3 4 5
6 I must not fail 1 2 3 4 5
7When overworked, I cannot say “no” to new
demands without guilt 1 2 3 4 5
8 I avoid being alone 1 2 3 4 5
9 I feel increasingly cynical and disenchanted 1 2 3 4 5
10 I am unable to laugh at a joke about myself 1 2 3 4 5
11 I avoid speaking my mind 1 2 3 4 5
12 I have trouble getting to sleep 1 2 3 4 5
13 I automatically express negative attitudes 1 2 3 4 5
14 I seem further behind at the end of the day than
when I started 1 2 3 4 5
15 I forget deadlines, appointments and personal
possessions 1 2 3 4 5
16 I am irritable, short-tempered, disappointed in the
people around me 1 2 3 4 5
17 Sex seems like more trouble than it’s worth 1 2 3 4 5
18 I consider myself exploited 1 2 3 4 5
19  1 2 3 4 5
20 I feel unrested. 1 2 3 4 5
       
the groups receiving the placebo versus the adaptogen/vitamin
supplement for 28 days using a paired 2-tailed t-test. Data are
expressed as the mean with the standard deviation. Differences

Results
The effects of 28 day supplementation with the adaptogen/
vitamin formulation on blood levels of HS-CRP, homocysteine
and cortisol are presented in Table 3. Daily supplementation for
2/5
Citation: Shara M, Kakish E, Stohs SJ (2017) Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers. Int J Complement
Alt Med 10(1): 00321. DOI: 10.15406/ijcam.2017.10.00321
Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers 3/5
Copyright:
©2017 Shara et al.
       
% as compared to the placebo control group. Daily use of the
      
% decrease in blood homocysteine levels and no effect on blood
cortisol.
Table 3: Effect of 28 day adaptogen/vitamin supplement vs placebo on
blood HS-CRP, homocysteine and cortisol levels.
Group HS-CRP Homocysteine Cortisol
Treated
Pre- 4.81±7.56 8.87+2.40 11.71±5.13
Post- 3.40±5.42 8.16±1.97 14.64 ±4.91
% Change Post-
30%
8%
25%
Placebo
Placebo 4.81±7.56 8.87+2.40 11.71±5.13
Post- 5.70±8.21 9.15±3.18 13.48±4.42
% Change Post-
18%
3.2%
15%
The data are also expressed based on the change in the number
of participants with abnormal laboratory values before and after
28 day treatment with the supplement or placebo control. As can
be seen in Table 4, a 40 % decrease occurred in the number of
participants with elevated HS-CRP after treatment as compared to
pre-treatment with the adaptogen/vitamin formulation. An 80 %
decrease occurred in the number of treated subjects with elevated
homocysteine after 28 days of treatment while a 33 % decrease

of participants with elevated blood cortisol after treatment with
the adaptogen/vitamin supplement or in the placebo group.
Table 4: Effect of 28 day adaptogen/vitamin supplementation on number
of participants with elevated lab values.
Number of Elevated/Abnormal Laboratory Values
Group HS-CRP Homocysteine Cortisol
Treated
Pre- 10 5 2
Post- 6 1 2
% Decrease Post- 40% 80% 0%
Placebo
Pre- 17 6 1
Post- 16 4 1
% Decrease Post- 5.90% 33% 0%
A stress perception questionnaire was administered on day 0
and day 28 of the study (Table 5). Five stress perception scores

%) in the participants supplemented with the adaptogen/vitamin
 
placebo group (questions 6 and 10).
Table 5: Effects of 28 day adaptogen/vitamin supplement vs. placebo on
stress survey.
Survey Parameter Mean Score
Group Q3 Q6 Q7 Q9 Q10
Treated
Pre- 2.6 3.7 3.4 2.9 2.5
Post- 2.2* 3.3* 2.9* 2.3* 2.0*
% Decrease Post- 15.4% 10.8% 14.7% 20.7% 20.0%
Placebo
Pre- 2.3 3.7 3.7 2.9 2.5
Post- 2.2 3.3* 3.2 2.5 2.0*
% Decrease Post- 4.30% 10.8% 13.5% 13.8% 20.0%
Discussion
          
reduction in HS-CRP blood levels in response to adaptogen/
vitamin ingestion for 28 days relative to the placebo control
(Tables 3), while a 40 % decrease occurred in the number of
treated subjects with elevated HS-CRP (Table 4). Furthermore,
       
preparation reduced stress perceptions to a greater extent than
the corresponding placebo (Table 5). Elevated HS-CRP is strongly
associated with an increased incidence of heart attack, stroke,
type 2 diabetes and metabolic syndrome [2,12,16-19], and the
       
these levels.
Hyperhomocysteinemia is associated with an increased risk
of cardiovascular disease, diabetes, osteoporosis, Alzheimer’s
disease, other dementias, and is also believed to be a marker
of pathological oxidant stress [20]. The administration of the
      
in blood homocysteine levels (Table 3), although the number
of subjects with elevated homocysteine levels at the start of
treatment decreased by 80 % after 28 days of product ingestion
(Table 4). Ingestion of B vitamins as vitamin B12, folate and
vitamin B6 (pyridoxine) as present in the product used in this
study have been shown to result in decreased blood homocysteine
levels [21]. As a consequence, it is not clear whether the decrease
in homocysteine in the current study was due to the B vitamins or
the adaptogen blend.
Cortisol levels are another indicator of stress [22], and
decreases in serum cortisol are believed to be produced by at least
some adaptogens [23]. For example, the adaptogen ashwagandha

decreased serum cortisol levels after 60 days of treatment [24].
The reason for the lack of an effect of the adaptogen/vitamin
product on cortisol levels after 28 days of treatment is not known.
The product did not contain ashwagandha.
A rapidly growing body of research literature supports the
   
Citation: Shara M, Kakish E, Stohs SJ (2017) Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers. Int J Complement
Alt Med 10(1): 00321. DOI: 10.15406/ijcam.2017.10.00321
Effects of an Adaptogen-Based Supplement on Stress Parameters in Healthy Volunteers 4/5
Copyright:
©2017 Shara et al.
     
and stress protective effects of adaptogens are believed to be
associated with the homeostatic regulation of several different
pathways and mechanisms including the hypothalamic-pituitary-
adrenal axis, the neuro-endocrine-immune complex, and key
stress response mediators [11,23,26]. The pharmacological
        
Wagner [9].
Up-regulation of the stress sensor heat shock protein (Hsp)
70 by adaptogenic substances results in the inhibition of the
       
enhancing mitochondrial antioxidant activity, glutathione
synthesis, and ATP generation [23,26]. Hsp 70 also interacts
directly with glucocorticoid receptors and controls key mediators
         
transcription factor forkhead box O (FOXO). A more recent
study by Panossian et al. [15] has shown that an adaptogenic
blend of extracts from Eleutherococcus, Shizandra and Rhodiola,
constituents present in the adaptogenic blend used in this study,
stimulated the expression of the stress hormone neuroprotein
           
these mechanistic effects is an increase in mental and physical
performance and possibly longevity [11,23,26]. The chemical
substances believed to be responsible for adaptogenic properties
include phenylpropanoids, phenethylamines and tetracyclic
triterpenoids [9,11]. Because of the widely diverse chemical nature
of adaptogens and their equally wide distribution throughout the
plant kingdom, combinations of adaptogenic plant extracts (Table
1) are commonly used in order to ensure a broad incorporation of
active constituents [9,11,14,15].
Conclusion
The use of the adaptogen/vitamin product for 28 days resulted


numbers of subjects with elevated HS-CRP and homocysteine.
      
observed in response to the adaptogen/vitamin blend based on
a perception survey.
Acknowledgment

Conict of Interest
This study was supported by a grant from AdvoCare
International, Plano, TX. SJS has served as a consultant for

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... The beneficial effects of Phytocee™ could be attributed to the collective effect of its individual ingredients viz E. officinalis, O. sanctum and W. somnifera which are rich in polyphenols, withanolides and triterpenoids. These phytochemical constituents are earlier proven to be responsible for antistress/adaptogenic effect [37][38][39][40] . These results also confirmed that Phytocee™ supplementation improves the resistance and endurance of shrimps through improving the energy status and immunity of shrimps as whole, hence results in better protection and survival as they are better prepared to face challenges. ...
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