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Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-optimal symptoms of physical and emotional health in young adults

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Purpose: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation, provide a dietary means of benefit. Methods: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three groups: placebo, 13 mg, or 27 mg / day total MCs. All parameters were assessed at baseline, 6 months, and 12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via questionnaire. Results: Significant baseline correlations were found between MPOD and Beck anxiety scores (r = -0.28; P = 0.032), MPOD and Brief Symptom Inventory scores (r = 0.27; P = 0.037), and serum cortisol and psychological stress scores (r = 0.46; P < 0.001). Supplementation for 6 months improved psychological stress, serum cortisol, and measures of emotional and physical health (P < 0.05 for all), versus placebo. These outcomes were either maintained or improved further at 12 months. Conclusions: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-optimal emotional and physical health. Determining the basis for these effects, whether systemic or a more central (i.e. brain) is a question that warrants further study.
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Nutritional Neuroscience
An International Journal on Nutrition, Diet and Nervous System
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Supplementation with macular carotenoids
reduces psychological stress, serum cortisol, and
sub-optimal symptoms of physical and emotional
health in young adults
Nicole Tressa Stringham, Philip V. Holmes & James M. Stringham
To cite this article: Nicole Tressa Stringham, Philip V. Holmes & James M. Stringham (2017):
Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and sub-
optimal symptoms of physical and emotional health in young adults, Nutritional Neuroscience, DOI:
10.1080/1028415X.2017.1286445
To link to this article: http://dx.doi.org/10.1080/1028415X.2017.1286445
Published online: 15 Feb 2017.
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Supplementation with macular carotenoids
reduces psychological stress, serum cortisol,
and sub-optimal symptoms of physical and
emotional health in young adults
Nicole Tressa Stringham 1,2, Philip V. Holmes1, 2, James M. Stringham 2
1
Interdisciplinary Neuroscience Program, Biomedical and Health Sciences Institute, University of Georgia,
Athens, GA 30602, USA,
2
Department of Psychology, University of Georgia, Athens, GA 30602, USA
Purpose: Oxidative stress and systemic inflammation are the root cause of several deleterious effects of
chronic psychological stress. We hypothesize that the antioxidant and anti-inflammatory capabilities of the
macular carotenoids (MCs) lutein, zeaxanthin, and meso-zeaxanthin could, via daily supplementation,
provide a dietary means of benefit.
Methods: A total of 59 young healthy subjects participated in a 12-month, double-blind, placebo-controlled
trial to evaluate the effects of MC supplementation on blood cortisol, psychological stress ratings, behavioural
measures of mood, and symptoms of sub-optimal health. Subjects were randomly assigned to one of three
groups: placebo, 13 mg, or 27 mg /day total MCs. All parameters were assessed at baseline, 6 months, and
12 months. Serum MCs were determined via HPLC, serum cortisol via ELISA, and macular pigment optical
density (MPOD) via customized heterochromatic flicker photometry. Behavioural data were obtained via
questionnaire.
Results: Significant baseline correlations were found between MPOD and Beck anxiety scores (r=0.28;
P=0.032), MPOD and Brief Symptom Inventory scores (r=0.27; P=0.037), and serum cortisol and
psychological stress scores (r=0.46; P<0.001). Supplementation for 6 months improved psychological
stress, serum cortisol, and measures of emotional and physical health (P<0.05 for all), versus placebo.
These outcomes were either maintained or improved further at 12 months.
Conclusions: Supplementation with the MCs significantly reduces stress, cortisol, and symptoms of sub-
optimal emotional and physical health. Determining the basis for these effects, whether systemic or a
more central (i.e. brain) is a question that warrants further study.
Keywords: Lutein, Zeaxanthin, Macular pigment, Stress, Cortisol, Anxiety, Depression, Health
Introduction
The basis for all stress responses is the disruption of
some homeostatic set point, be it physical, physiologi-
cal, or psychological.
1
Physiologically, stress is associ-
ated with activation of autonomic and endocrine
systems,
2,3
which involves limbic, hypothalamic,
and brainstem circuits.
4
Chronic activation of these
systems may manifest as anxiety disorders
4,5
or other
stress-related disorders, such as depression.
6
Indeed,
the link between anxiety and chronic activation of
the limbic structures, such as the amygdaloid
complex, has been well established.
7
Psychologically,
the basis of anxiety and depression may involve
heightened vulnerability to stress or the inability to
cope with life stressors
8
and appears to be mediated
by dysregulation in cortico-limbic circuitry.
9
The convergence of physiological, psychological,
and neurological data in the case of stress, anxiety,
and depression is compelling. In fact, the basis for the
Depression Anxiety Stress Scales 21 (DASS-21)
10
is
the tripartite model,in which anxiety and depression
are both related to psychological stress: Anxiety arises
out of physiological hyperarousal, whereas depression
arises from low positive affectivity, both being impacted
by the negative affect brought on by stress. It appears,
therefore, that although anxiety and depression are
somewhat discrete phenomena, they both share a
common root in psychological stress .
5,11
This idea is
further supported by comorbidity rates exceeding
50%.
12
Susceptibility to stress could, therefore, be
Correspondence to: Nicole Tressa Stringham, Interdisciplinary
Neuroscience Program, Biomedical and Health Sciences Institute and
Department of Psychology, University of Georgia, Athens, GA 30602, USA
Email: ntwood@uga.edu
©2017InformaUKLimited,tradingasTaylor&FrancisGroup
DOI 10.1080/1028415X.2017.1286445 Nutritional Neuroscience 2017 1
considered to be a risk factor for those conditions, such
as anxiety and depression, that appear to result from
excessive psychological stress.
It has been suggested that dietary differences could
modulate susceptibility to stress.
13
Benton
14
noted
that effects of minor nutritional deficiencies would
manifest first as sub-clinical disruption of brain func-
tion, given the complexity and metabolic demands of
the brain. In general support of this idea, there have
been recent human and animal studies that report
stress-reducing effects of supplementation of specific
nutrients, such as curcumin,
15
alpha tocopherol,
16
and docosahexaenoic acid (DHA).
17
In each case, sup-
plementation appears to lead to reduced psychological
stress and physiological parameters of stress (e.g.
blood cortisol). Additionally, Long and Benton
18
con-
ducted a meta-analysis of studies on the effects of
vitamin and mineral supplementation on stress and
mood in sub-clinical populations, and found a
general trend towards stress reduction and improve-
ment in mood.
A recent report by El Ansari et al.
19
on a large
(n=3706), generally healthy population of college-
aged adults examined, via survey, dietary patterns and
stress /depressive symptoms. They found a significant
relationship between consumption of healthy foods
(fresh fruits, salads, and cooked vegetables) and
reduced perceived psychological stress. Conversely,
consumption of junkfood was associated with
increased perceived psychological stress. Although
these findings were correlational, there is a physiologi-
cal rationale to account for how healthy foods may
reduce psychological stress: consumption of antioxi-
dants. It has been shown that systemic oxidative stress
is induced by psychological stress (e.g. in medical stu-
dents
20
), and it appears that reduction of systemic oxi-
dative stress significantly reduces indicators of
psychological stress (via alpha-tocopherol adminis-
tration;
21
and by lutein
22
). Of particular relevance to
the present study, Yajima et al.
22
reported that lutein
(L) supplementation produced an anxiolytic-like
effect in mice exposed to constant illumination stress.
Taken together, these findings suggest a role for
dietary antioxidants in reducing psychological stress.
Based on the idea that any form of homeostatic upset
will produce a similar stress response in the body,
1
it is
perhaps the case that a situation, favouring oxidative
stress within the body, may produce an alarm state,
which may ultimately be interpreted psychologically
as uneasiness, or stress. Although the specific neurophy-
siological mechanisms are undoubtedly complex, we
believe this general idea to be plausible, based on
what is known in the literature on the matter.
Carotenoids, such as L, comprise a fairly large pro-
portion of dietary antioxidants for humans with a
reasonably healthy diet that includes daily
consumption of fruits and vegetables.
23
Along with
L, two other yellow-orange carotenoids, zeaxanthin
(Z), and meso-zeaxanthin (MZ) are deposited in rich
concentration in the central retina, where they form
the macular pigment (MP).
24
MP is most dense in
the metabolically intense central retina (fovea),
where its powerful antioxidant
25
and high-energy
short-wave light filtration properties
26
appear to
protect the macula from acute damage,
27
protect
against cumulative damage resulting in age-related
macular disease,
28
and maintain visual sensitivity
over a lifetime.
29
MP is strictly derived via diet, and
so a persons level of MP is dependent upon his or
her consumption of foods that contain these caroten-
oids; for example, dark leafy-green vegetables, such
as kale and spinach, are excellent sources of L.
30
L
and Z also accumulate in the brain,
31,32
where they
may influence cognitive performance, especially in
aged individuals.
3335
In a manner apparently similar
to the retina, L and Z cross the bloodbrain barrier
and accumulate in the brain regions that maintain rela-
tively high metabolism (e.g. frontal and occipital
lobes, and hippocampus), and are therefore at higher
risk for oxidative stress and inflammation.
36
Importantly, MPOD has been shown to be signifi-
cantly correlated with brain levels of L and Z,
32
which suggests similar mechanisms of uptake, and
supports the idea that there is preferential deposition
of these powerful antioxidants /anti-inflammatories
in neural tissues that maintain high metabolism and
therefore concomitant oxygen tension and potential
for oxidative stress and inflammation.
There were two goals of the present study: (1) To
determine, in healthy young adults, the relationship
at baseline between MPOD and psychological stress
level, serum cortisol, and symptoms of sub-optimal
emotional and physical health, and (2) To determine
the effect of 12 monthsL, Z, and MZ supplemen-
tation on the aforementioned parameters. Once depos-
ited in retinal tissue, L and Z (the two primary dietary
components of macular pigment
37
) are quite stable in
the absence of high oxidative stress, e.g. such as that
brought on by smoking
38
or diabetes.
39
Therefore, a
persons macular pigment level is generally thought
to reflect his or her lifelong consumption of L and
Z. The baseline assessment of MPOD and psychologi-
cal stress, and physical /emotional health status
would thereby enable the analysis of potential cumu-
lative effects of diet on these outcome parameters. In
contrast, the 12-month supplementation trial enabled
the analysis of potential acute effects of MC
supplementation.
Methods
Fifty-nine subjects participated in this 12-month,
double-blind, randomized, placebo-controlled
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017
2
supplementation trial. Subjects were generally healthy,
college-aged (1825, mean =21.5 years; 27 males /32
female) non-smokers with a BMI <27. Subjects were
instructed to maintain their current diet; those who
were planning on changing their diet ( for whatever
reason) were excluded from consideration for the
trial. In consideration of macular pigment testing, all
subjects had uncorrected or contact lens-corrected
visual acuity of 20/20 or better in the test (right) eye,
and had no current or previous history of ocular path-
ology. Subjects were recruited from the population of
students at the University of Georgia in Athens,
Georgia. Informed consent was obtained from each
subject and the study adhered to the tenets of the
Declaration of Helsinki. The study was approved by
the Institutional Review Board of the University of
Georgia.
Several parameters were assessed over the course of
the study, including retinal status of MCs, serum cor-
tisol, serum lutein, serum zeaxanthin isomers.
Symptoms of sub-optimal health, psychological
health, and emotional health were assessed via ques-
tionnaire (see Table 1for a summary of questionnaires
used in the study and order of administration). All
measures were taken at baseline, 6 months, and 12
months. Laboratory visits included (in order): blood
draw, questionnaire completion, and vision testing.
Macular carotenoid supplementation
Subjects were randomly assigned to one of three
groups: placebo, n=10; 13 mg/day MC, n=24; or
27 mg/day MC. Pills were brown coloured, soft
gelatin capsules, with L, Z, and MZ suspended in saf-
flower oil. Independent analysis indicated that the
13 mg supplement contained 10.86 mg lutein /
2.27 mg zeaxanthin isomers, and the 27 mg sup-
plement contained 22.33 mg lutein /4.70 mg zeax-
anthin isomers. Placebos contained no L or Z
isomers, only safflower oil. Z and MZ were found in
roughly equal amounts in the active supplements. All
reported values were within ±5% variability.
Subjects were instructed to ingest one pill with a
meal ( preferably lunch or dinner) every day.
Compliance was ensured with weekly phone calls
and pill counts.
Measurement of macular pigment optical
density (MPOD)
The concentration of MCs in the central retina
(MPOD) was assessed with a non-invasive, perceptual
task called heterochromatic flicker photometry (HFP).
A densitometer (Macular Metrics Corp., Rehoboth,
MA) described by Wooten et al.
40
was used for this
purpose. The densitometer, detailed measurement pro-
cedures, and the principle of HFP have been fully
described in earlier publications.
41,42
Briefly, subjects
are presented with two superimposed lights that are
temporally alternated in square-wave counterphase.
This gives the subject an impression on a flickering
disc of light. The peak (550 nm) of the spectral compo-
sition of one of the lights is chosen to bypass the
absorption of MP, and the other (460 nm) is strongly
absorbed by MP. The subjects task is to adjust the
relative radiance of the two lights until a percept of
no flicker is achieved. All other factors being equal,
a subject that requires more short-wave (i.e. 460 nm)
relative to middle-wave (i.e. 550 nm) light to achieve
null flicker has higher MPOD. This task is performed
for the locations of interest within the fovea, which
presumably contain MP, and for a reference location
in the parafovea that does not (about 7° eccentricity).
To obtain a measure of MPOD at a given test locus,
the logarithmic ratio of short- to middle-wave radiance
(for null flicker) at the reference location is subtracted
from the corresponding logarithmic ratio found at the
test locus.
Blood collection
Fasting blood was collected between 9 am and 11 am,
by a licensed phlebotomist, at baseline, 6-month, and
12-month visits. Subjectswhole blood was collected
into a serum separator vacutainer tube (SST) via veni-
puncture. Blood was allowed to clot for 30 minutes at
room temperature before centrifugation for 15 minutes
at 1000 ×g. Serum was then removed and stored in
microvials at 20° C until analysis.
High-performance liquid chromatography
(HPLC)
Sample extractions and analyses were completed
under yellow light. Serum proteins were precipitated
with an equal volume of ethanol (1% BHT), contain-
ing the internal standard, trans-β-apo-8-carotenal.
After centrifugation, samples were extracted three
times with n-hexanes, mixing, and centrifugation.
Organic layers were pooled and evaporated to
dryness with nitrogen and re-suspended in the
mobile phase. An Agilent 1200 series HPLC system,
consisting of a quaternary pump with degasser, auto-
sampler, thermostated column compartment, UVvis
diode array detection (DAD) with standard flow
cell, and 3D ChemStation software (Agilent
Technologies, Santa Clara, CA, USA), was employed
for the chromatography. A reversed-phase YMC C30
column (4.6 ×250 mm, 5-μm particle size) was uti-
lized. A stepwise elution consisting of mobile phase
A (95% methanol) and mobile phase B (methyl tert-
butyl ether) from 15 to 85% B over a 27-minute
period at a flow rate of 1 mL/min was employed. A
volume of 100 μL was injected for each of the serum
samples. Detection wavelengths were λ=447 nm (L)
and 450 nm (Z isomers).
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017 3
Enzyme-linked immunosorbent assay (ELISA)
Serum was diluted and processed according to the
manufacturers instructions for the Parameter
Cortisol Human ELISA kit (KGE008, R&D
Systems, Minneapolis MN, USA). Wells were read at
450 nm (MiniReader MR590, Dynatech Instruments,
Inc, Santa Monica CA, USA), averaged across dupli-
cates, and a curve of best fit was used to calibrate to
standards. Cortisol concentration data are reported
as ng/mL. All coefficient of variability values were
under 10%.
Psychological stress measure
Subjectspsychological stress level was assessed via
questionnaire with the 9-item Psychological Stress
Measure (PSM-9).
43
Brief symptom inventory
Subjectscurrent psychological distress was assessed
with the Brief Symptom Inventory (BSI),
44
a 53-
item, self-report instrument developed from the
longer SCL-90-R.
Beck anxiety inventory
Subjectssymptoms of anxiety were assessed with the
Beck Anxiety Inventory (BAI),
45
a 21-item self-
report instrument that is validated for measuring the
severity of anxiety.
Beck depression inventory
Subjectssymptoms of depression were assessed with
the Beck Depression Inventory (BDI),
46
a 21-item
self-report instrument that is validated for measuring
the severity of depression.
General health status
The number of physical symptoms of sub-optimal
health was determined via self-report questionnaire,
using the 25-item Suboptimal Health Status
Questionnaire (SHSQ-25).
47
Statistical analysis
Graphs and statistical analysis, including descriptive
statistics, Pearson product-moment correlations,
dependent-samples t-tests, and Repeated-Measures
ANOVA were generated using Origin software
(Northampton, MA, USA). Statistical significance
was determined at the P=0.05 level. The number of
subjects required to detect effects (if present) was cal-
culated via power analysis, which was based on a
20% change in the composite outcome measure of
psychological stress /cortisol, and assumed a
placebo group with n=10.
Results
At baseline, significant correlations were determined
between MPOD and BAI scores (r=0.28; P=
0.032 see Table 2), MPOD and BSI scores
(r=0.27; P=0.037 see Table 2), and between
serum cortisol and PSM-9 scores (r=0.46; P<0.001
see Fig. 1). Although not statistically significant,
marginal correlations were determined at baseline for
MPOD and serum cortisol (r=0.202; P=0.124),
MPOD and psychological stress (r=0.218; P=
0.10), and MPOD and symptoms of sub-optimal
health (r=0.22; P=0.092). See Table 2for a
summary of baseline and supplementation effects for
all behavioural measures.
After 6 months of MC supplementation, repeated-
measures ANOVA revealed that there were no signifi-
cant beneficial changes from baseline in any parameter
for the placebo group. At 6 months, however, serum
cortisol was found to increase significantly from base-
line. This change did not persist, and returned to base-
line levels at 12 months (see Fig. 2). For the 13 mg/day
group however, we found that MPOD (P<0.001) was
significantly higher (see Fig. 2), and serum cortisol
(P<0.001 see Fig. 2), BSI scores (P=0.005), and
number of sub-optimal health symptoms (P=
0.0012) were significantly lower compared to baseline.
The 27 mg/day group was found to significantly
increase in MPOD (P<0.001 see Fig. 2), and
Table 1 Summary of self-report questionnaires used during the course of the study
Instrument Items Outcome measure
Range of
scores
Cronbachs
α
Test/retest
reliability Published Order
PSM-9 Psychological Stress
Measure 9
9 Stress in general
population
972 0.95 0.688 Lemyre et al.
43
5
BSI Brief Symptom
Inventory
53 Current
psychological
distress
0212 0.71-0.85 0.6891 Derogatis and
Melisaratos
44
1
BAI Beck Anxiety
Inventory
21 Severity of anxiety 063 0.92 0.75 Beck et al.
45
2
BDI Beck Depression
Inventory
21 Severity of
depression
063 0.86 0.93 Beck et al.
46
3
SHSQ-25 Suboptimal Health
Status
Questionnaire
25 Suboptimal Health
Status
25125 0.93 0.8998 Yan et al.
47
4
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017
4
Table 2 Relation of each self-report measure (PSM-9, BSI, BAI, and SHSQ-25) to MPOD at baseline, and descriptive statistics for each time point as a function of MC dose
Measure Psychological Stress Measure (PSM-9) Brief Symptom Inventory (BSI) Beck Anxiety Inventory (BAI)
Baseline relation to MPOD r=0.218; P=0.10 r=0.27; P=0.037 r=0.28; P=0.032
Time point Baseline 6 months 12 months Baseline 6 months 12 months Baseline 6 months 12 months
Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD
0mg/day MC 26.7 6.43 29.1 5.07 30.1 7.39 18.1 14.22 17.2 13.27 17.5 14.18 8.7 5.89 8.4 6.2 8.6 6.08
13 mg/day MC 31.83 7.38 31.38 6.64 26.96
a
5.25 23 11.07 17.96
a
11.34 12.92
a,b
9.74 7.54 5.36 6.54 4.89 4.33
a,b
3.69
27 mg/day MC 31.44 10.24 27.76
a
6.73 27.4
a
7.67 27.4 18 20.12
a
14.07 13.44
a,b
12.22 6.48 5.87 4.32
a
4.29 2.96
a,b
3.42
Measure Beck Depression Inventory (BDI) Suboptimal Health Status Questionnaire (SHSQ-25)
Baseline relation to MPOD r=0.078; P0.671 r=0.22; P=0.092
Time point Baseline 6 months 12 months Baseline 6 months 12 months
Mean SD Mean SD Mean SD Mean SD Mean SD Mean SD
0mg/day MC 5.3 8.01 5.2 11.77 5.2 13 30.3 7.93 29.9 4.89 30.4 7.82
13 mg/day MC 4.83 3.57 3.79 3.5 3.42 4.03 37.79 7.92 34
a
7.11 32.63
a,b
7.41
27 mg/day MC 4.2 4.03 3.36 3.32 2.4
a
3.18 37.76 10 34.64
a
9.23 33.28
a
7.49
a
P<0.05 compared to baseline.
b
P<0.05 compared to 6 months.
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017 5
decrease significantly for the BSI (P=0.009 see
Table 2), BAI scores (P<0.001 see Table 2), psycho-
logical stress (P=0.05 see Fig. 2), serum cortisol
(P=0.01 see Fig. 2), and number of sub-optimal
health symptoms (P<0.001 see Table 2).
There were no significant changes from baseline
determined for any measure in the placebo group at
12 months. For the 13 mg/day group, a significant
increase from 6 months to 12 months was found for
MPOD (P<0.001 see Fig. 2), and significant
decreases were determined for BSI scores (P=0.002
see Table 2), BAI scores (P=0.013 see Table 2),
psychological stress (P=0.018 see Fig. 2), serum
cortisol (P=0.0037 see Fig. 2), and number of
sub-optimal health symptoms (P=0.007 see
Table 2). Comparing 6- and 12-month measures, the
27 mg/day MC increased significantly in terms of
MPOD (P=0.0087 see Fig. 2), and decreased sig-
nificantly for the BSI (P=0.013see Table 2), the
BAI (P=0.038see Table 2), serum cortisol (P=
0.037 see Fig. 2), and symptoms of sub-optimal
health (P=0.041see Table 2). A significant decrease
in scores on the PSM-9 and BDI was determined at 12
months for the 27 mg/day MC group when compared
to baseline (P=0.05 and 0.025; see Fig. 2and Table 2,
respectively).
Repeated-measures ANOVA determined that serum
L and Z isomers increased significantly after 6 months
of supplementation for both active supplement groups
(P<0.001; see Figs 3and 4, respectively) versus
placebo, and maintained an apparent steady-state
Figure 1 Baseline correlation between serum cortisol (ng/
mL) and PSM-9 scores. Dotted line least-squares fit to data.
Figure 2 MPOD, Serum cortisol, and PSM-9 scores for all groups, as a function of time in the study. Reported as percent change
from baseline. Means ±SEM plotted for baseline, 6- month, and 12- month measures.
Figure 3 Serum lutein concentration as a function of time in
the study, for all groups. Means ±SEM for baseline, 6-month,
and 12- month measures.
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017
6
level at 12 months. As can be seen in Fig. 3, the steady-
state L serum level was found to be roughly 2.25 μg/
mL for the 13 mg/day MC group, and 3.25 μg/mL
for the 27 mg/day MC group. The placebo group
remained at a concentration of approximately
0.25 μg/mL throughout the 12-month study period.
The change in serum concentration of Z isomers was
also found to be significant at 6 months (P<0.001)
and, as in the case of L, maintained the 6-month
level through 12 months (see Fig. 4). From Fig. 4,it
can be seen that the Z isomer steady-state level for
the 13 mg/day MC group was 0.37 μg/mL, and
0.47 μg/mL for the 27 mg/day MC group. The
placebo group remained at a concentration of
roughly 0.10 μg/mL throughout the study.
As noted above, MPOD increased significantly
from baseline at 6 months, and from 6 months to 12
months in both 13- and 27- mg/day MC groups (see
Fig. 2). Despite double the amount of carotenoid in
the 27 mg/day MC groups supplement (27 mg vs.
13 mg), retinal response across the study period was
virtually identical for both groups.
In terms of change in measures over the 12-month
study period, the relationship between increases in
MPOD and decreases in serum cortisol was found to
be significant (r=0.454; P<0.001; see Fig. 5).
This same relationship was found for psychological
stress, where increases in MPOD were significantly
related to reduced PSM-9 scores (r=0.398; P=
0.002 see Fig. 6). This kind of relationship with
change in MPOD was not found for the other behav-
ioural measures. There were, however, nearly signifi-
cant relationships determined between the change in
symptoms of sub-optimal health and psychological
stress (P=0.08), and cortisol (P=0.07), respectively.
The finding of a relationship between cortisol and
sub-optimal health symptoms was also determined
by Yan et al.,
48
using the same scale (SHSQ-25) as
the present study.
Discussion
Given the results of this study, it appears that there is a
significant role for diet, specifically the MCs, in redu-
cing stress and improving symptoms of both physical
and emotional health. Although similar improvements
were determined for all outcome measures over the
course of the study in both active supplement groups,
measures of stress (serum cortisol and PSM-9) were
the only measures that were related directly to increases
in MPOD. The mechanism for the stress reduction
effects appears, therefore, to be related to the accumu-
lation of the MCs in the retina (and presumably the
brain). Given the biochemical properties of the MCs,
a plausible mechanism for this finding may involve
the direct antioxidant and anti-inflammatory action
within specific neural tissues that ultimately leads to
production of stress-related hormones. Additionally
(as suggested in the Introduction section), it could be
that the presumed reduction of systemic or local
neural oxidative stress via L, Z, and MZ supplemen-
tation effectively produced lower physiological stress,
which led to reduced psychological stress. As for the
measures related to mood (BAI, BDI, BSI) and physical
health (SHSQ-25), there was a clear benefit of sup-
plementation with the MCs, but the improvements
were not directly related to the change in MPOD. If
retinal /brain deposition of L, Z, and MZ, does not
account for the improvements in physical /emotional
health symptoms, then it would seem plausible that
changes in systemic (i.e. serum) carotenoid levels
could explain the effects. But changes in serum caroten-
oid levels were not directly related to changes in
physical /emotional health symptoms. There are
several possible reasons for this. It may be that differ-
ences in systemic oxidative stress and inflammation
among participants served to modify serum carotenoid
levels in such a way as to mask any relationship
between mood /health scales and serum carotenoid
Figure 4 Serum zeaxanthin concentration as a function of
time in the study, for all groups. Means ±SEM for baseline,
6-month, and 12- month measures
Figure 5 Change in serum cortisol over the 12-month study
period as a function of change in MPOD over the same time
period. Dotted line least-squares fit to data.
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017 7
concentration. Alternatively, retinal and brain caroten-
oid transport efficiency differs substantially between
individuals,
24
and this may have impacted serum
levels in a non-systematic way. Additionally, serum
carotenoid concentrations for a supplementation trial,
such as the present study, tend to saturate by about 12
weeks of daily supplementation.
49,50
Therefore, corre-
lations involving analysis of change would be limited,
due to the fact that our subjects probably reached
serum saturation long before their second measure (6
months). Lastly, and perhaps most parsimoniously,
the reduced psychological stress levels seen in our treat-
ment groups may have served to reduce symptoms of
anxiety, depression, and sub-optimal health symptoms
in a manner that is not related to our serum measures
of either cortisol or carotenoids. Whatever the case,
the effects found in our study are consistent with
either systemic or neural tissue elevation of MCs.
Based on our supplementation data for serum and
MPOD, it appears that deposition in neural tissues
requires a consistent, relatively elevated serum concen-
tration of L, Z, and MZ that the placebo group
(which did not exhibit improvements in any outcome
parameter) did not increase in either serum or MPOD
speaks convincingly to this point.
MPOD response to supplementation in both active
supplement groups was very similar, despite the
higher dose supplement containing roughly double
the amount of carotenoids. Serum response was
about 30% higher for the 27 mg/day MC group,
which indicates that the additional carotenoids either
remained higher in serum, or were deposited in other
tissues, such as skin or adipose tissue. Another possi-
bility is that, despite random assignment, participants
assigned to 13 mg/day MC group tended to (overall)
respond more favourably in the retina, compared to
those in 27 mg/day MC group. Variability in retinal
response to supplementation with retinal carotenoids
has been shown previously.
24
Moreover, retinal
response typically is found to increase somewhat line-
arly with increased dose.
24,50
Although the results of
these previous studies are difficult to reconcile with
the present results, retinal response was nevertheless
robust in both active supplement groups.
Taken together, the cross-sectional and supplemen-
tation-trial data make a strong case for the involve-
ment of L, Z, and MZ in psychological stress levels
and physical /emotional health symptoms. In terms
of stress and physical health, given the well-established
relationship between psychological stress and compro-
mised immune function, it is quite possible that the
reduction in sub-optimal health symptoms over the
period of the study is an effect subsequent to the
reduction in stress seen with supplementation.
Support for this possibility is provided by the baseline
relationship between psychological stress level and
number of sub-optimal health symptoms (r=0.415;
P=0.0011 see Fig. 7). The nearly significant
relationships between change in symptoms of sub-
optimal health and change in both serum cortisol
(r=0.24; P=0.07), and change in psychological
stress (P=0.08) over the study period is further evi-
dence for this idea.
Cortisol is the effector hormone of the hypothala-
mic-pituitary-adrenal (HPA) axis (the stressaxis),
and widely considered to be an excellent physiological
marker for psychological stress.
2
We determined a
marginally significant relationship between MPOD
and serum cortisol at baseline (P=0.124), and a
strongly significant relationship between change in
MPOD and change in serum cortisol for all subjects
over the study period (r=0.454; P<0.001). As
noted above, however, the effect of cortisol reduction
was not related to serum carotenoid response. In
other words, a subjects blood response was somewhat
Figure 6 Change in PSM-9 score over the 12-month study
period, as a function of change in MPOD over the same time
period. Dotted line least-squares fit to data.
Figure 7 Baseline SHSQ-25 scores (higher scores=greater
number of sub-optimal health symptoms), as a function of
baseline PSM-9 scores. Dotted line least-squares fit to data.
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017
8
independent of cortisol reduction over the study
period. This apparent discrepancy could be explained
by the fact that the effect of stress reduction is driven
by the neural (presumably brain) deposition of these
carotenoids, and that this deposition may lead to
modulation of the HPA axis. The mechanism for this
could involve a local reduction of inflammation,
which has been previously shown to be closely linked
with stress.
51
Additionally, corticosteroids generated
from the stress response decrease the effectiveness of
endogenous antioxidant systems.
52
Because dietary
antioxidants, such as L and Z, supplement endogen-
ous antioxidant systems, such as glutathione and
superoxide dismutase,
53
it could be that local
reduction of both oxidation and inflammation (via L
and Z) plays a role in the cortisol and stress reduction
effects found in our study.
Serum cortisol concentration increased signifi-
cantly from baseline in the placebo group at
6months,andthenreturnedtobaselinelevelsat
12 months (see Fig. 2). This may be due to a seasonal
effect of variation in serum cortisol,
54
as the 6-month
measure fell within the months when cortisol is
reportedly elevated in healthy subjects. Nevertheless,
both supplementation groupsserum cortisol
decreased at both 6 and 12 months, suggesting an
overall long-term effect of L, Z, and MZ supplemen-
tation on serum cortisol.
That such specific nutrients are able to confer sub-
stantial and meaningful effects over a relatively short
time period could be interpreted in several ways.
First, it could be that human beings were meant to
consume significantly more foods (e.g. leafy-green veg-
etables) that contain these carotenoids than is cur-
rently the case.
55
Our serum data from the baseline
measure of our entire sample are indicative of low
intake (overall) of L, Z, and MZ. Indeed, data from
the National Health and Nutrition Examination
Survey (NHANES, 2003, as cited in Johnson
et al.
55
) indicate that Americans in the age range
(1930 years.) corresponding to our subjectsgeneral
age range consume a paltry 1.5 mg of L and Z daily.
At such low levels of consumption, the body may
use any available carotenoid for more immediate, sys-
temic purposes (e.g. inflammation, or oxidative stress)
rather than depositing it in tissues such as the retina or
brain (where our data suggest stress-reducing effects).
Perhaps, our intervention simply brought serum
MCs, MPOD (and brain carotenoid) levels up to a
point that facilitated relatively normalfunction. In
terms of psychological stress and cortisol, this point
can be argued not only from the standpoint of the
intervention but also from the cross-sectional analysis,
where subjects with higher levels of MPOD were found
to have marginally significantly lower psychological
stress levels and serum cortisol (see Table 2).
In addition to low baseline dietary intake of L, Z,
and MZ, another consideration for our findings is
the level of stress experienced by the study partici-
pants. Our subjects were young and healthy, but never-
theless experienced relatively high levels of
psychological stress, and reported a fair number of
sub-optimal physical and emotional health symptoms.
Stressful situations most often noted by subjects were
struggles with coursework (e.g. worrying about
grades), relationship problems, and worrying about
money. It may be the case that college students experi-
ence higher-than-average stress (and subsequent nega-
tive health symptoms) than the overall population. If
the MCs serve a function of reducing serum cortisol
and stress, then it follows logically that supplemen-
tation in individuals experiencing relatively high
levels of stress would produce acute benefits.
As with any study, caution should be exercised
before extending these results to other populations.
Although there are advantages in terms of experimen-
tal control to studying a fairly homogeneous group, it
can limit external validity. Our subjects were similar
along many dimensions, including age, BMI, edu-
cation level, and current life status (i.e. college
student); our findings may therefore hold true for
this group, but may not extend to others.
Additionally, it may be tempting to interpret the be-
havioural data (BAI, BDI, and BSI) as evidence for
the ability of MC supplementation to reduce anxiety
or depression. None of our subjects were diagnosed
with depression or an anxiety disorder. Our results
simply suggest that supplementation with the MCs
can reduce symptoms (however few) of anxiety and /
or depression. In order to address other populations
(e.g. clinically anxious or depressed individuals),
additional studies would need to be conducted. In
the future, we hope to investigate the effects character-
ized in the present study in subjects with different life-
style and dietary habits, in different age groups, and
different socioeconomic backgrounds.
Disclaimer statement
Contributors Author N.T.S. contributed to experimen-
tal design, data collection, blood collection and analy-
sis, data analysis, and writing of the manuscript.
Author P.V.H. contributed to experimental design
and manuscript writing. Author J.M.S. contributed
to experimental design, data collection, data analysis,
and writing of the manuscript.
Funding Omniactive Health Technologies, Inc.
Conflict of interest None.
Ethics approval The study was approved by the
Institutional Review Board of the University of
Georgia.
Stringham et al. Macular carotenoids and stress
Nutritional Neuroscience 2017 9
ORCID
Nicole Tressa Stringham http://orcid.org/0000-
0003-1721-7882
James M. Stringham http:// orcid.org/0000-0002-
1476-1084
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... However, alterations in macular pigment status have been posited as a surrogate for visual performance in both healthy and diseased states [231,269]. Maintaining greater MPOD levels have been shown to improve several functional outcomes that likely correspond with symptoms of asthenopia, including: light sensitivity (photophobia) [270,271], glare disability [269,272,273], and photostress recovery [269,[272][273][274], along with visual temporal resolution [275][276][277] and contrast sensitivity [269,[278][279][280][281]. Baseline correlations from available reports indicate MPOD was significantly associated with eye strain frequency, as well as psychological stress scores, in addition to these visual outcome measures [268,282,283]. Therefore, evidence from preliminary trials wherein carotenoid vitamin therapy is found to enhance macular pigment concentrations with concomitant benefits in visual performance, may be clinically relevant for treating individuals with digital eye strain (Table 3). ...
... Following a repeated-exposure measure to emulate the dynamics of photostress recovery, substantially faster and more consistent visual recovery performance was observed among those with greater MPOD [282]. Hence, the therapeutic potential for carotenoid vitamin therapy in digital eye strain to augment macular pigment concentrations appear to facilitate an optimal state of visual adaptation under exceedingly bright light conditions (i.e., LED displays) [268,278,282,283,293,295,311]. ...
... Furthermore, therapeutic strategies aimed at enhancing macular xanthophyll concentrations are thought to play an important role in alleviating psychological stress as well as promoting both physical and mental well-being. Following long-term supplementation with all three macular carotenoids, clinical studies observed remarkable benefits in serum cortisol, reduced anxiety scores, and improvement in overall sleep quality among healthy young adults [268,283]. Researchers suggest the observed effect on cortisol reduction following carotenoid vitamin therapy may involve anti-inflammatory actions within local neurosensory tissues thereby counteracting the physiological implications associated with the stress response [283,312]. For example, previous reports have reported marked inhibition of the endogenous antioxidant system in consequence of stress-induced corticosteroid production [312,313]. ...
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Digital eye strain is a complex, multifactorial condition that can be caused by excessive screen time exposure to various electronic devices such as smartphones, tablets, e-readers, and computers. Current literature suggests oxidative damage concomitant with a chronic pro-inflammatory state represent significant etiopathogenic mechanisms. The present review aims to discuss the potential dietary role for micronutrients with nutraceutical properties to ameliorate various ocular and vision-related symptoms associated with digital eye strain. For ocular surface dysfunction, enhanced anti-inflammatory benefits with omega-3 polyunsaturated fatty acids have been well documented for treatment of dry eye disease. The anti-oxidative and immunosuppressive properties of anthocyanin phytochemicals may also confer protective effects against visually induced cognitive stress and digital asthenopia. Meanwhile, nutraceutical strategies involving xanthophyll macular carotenoids demonstrate enhanced cognitive functioning and overall visual performance that aids digital eye strain. Collectively, preliminary findings seem to offer a strong line of evidence to substantiate the need for additional randomized controlled trials aimed at treating digital eye strain with adjunctive nutraceutical strategies. Further RCT and comparisons on commercially available nutritional supplements are needed to quantify the clinical benefits.
... Our review expands the scope of this review by including dietary sources of lutein and/or zeaxanthin, including other study designs in addition to randomized controlled trials (RCTs), and evaluating additional subgroups. Additionally, several new studies have been published in recent years, particularly studies with a longer duration of follow-up or larger sample sizes (7)(8)(9)(10)(11)(12). ...
... Supplemental Tables 2 and 3 detail the trial and participant characteristics of the RCT and nonrandomized studies, respectively. Six studies evaluated dietary interventions (25)(26)(27)(28)(29)(30), 38 evaluated supplements (7)(8)(9)(10)(11)(12), and 2 compared a dietary intervention with a supplement (63, 64) ( Table 1). Study duration ranged from 5 wk to 24 mo. ...
... Seven randomized placebo-controlled trials were not included in the meta-analysis because they did not report sufficient information (8,12,35,37,44) or because they used autofluorescence to measure MPOD (9,34). Results from these studies are generally consistent with the conclusion that intake of lutein/zeaxanthin, especially at higher doses, increases MPOD in the fovea (Supplemental Table 5). ...
Article
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Lutein, zeaxanthin, and meso-zeaxanthin are the only carotenoids found in the human macula and may have a role in visual function. These carotenoids are reported to protect the retina, and thus vision, as antioxidants and by acting as a blue light filter. Our objective was to determine a minimum concentration of lutein/zeaxanthin intake that is associated with a statistically significant and/or clinically important change in macular pigment optical density (MPOD) among adults with healthy eyes. We searched Ovid MEDLINE, CENTRAL, and the Commonwealth of Agriculture Bureau for English-language studies through to July 2020. Two reviewers screened results to identify studies that evaluated supplements or dietary sources of lutein/zeaxanthin on MPOD among adults with healthy eyes. One reviewer extracted data and assessed strength of evidence, which was confirmed by a second reviewer. Two independent reviewers assessed the risk of bias. Meta-analyses were stratified by total lutein/zeaxanthin dose. We included 46 studies (N = 3189 participants; mean age = 43 y; 42% male). There was no statistically significant change in MPOD among studies evaluating <5 mg/d of total lutein/zeaxanthin intake which primarily assessed dietary interventions for 3–6 mo (pooled mean difference, 0.02; 95% CI: –0.01 to 0.05). The pooled mean increase in MPOD was 0.04 units (95% CI: 0.02 to 0.07) among studies evaluating 5 to <20 mg/d of lutein/zeaxanthin and was 0.11 units (95% CI: 0.06 to 0.16) among studies evaluating ≥20 mg/d of lutein/zeaxanthin for 3–12 mo. MPOD increased with lutein/zeaxanthin intake, particularly at higher doses, among adults with healthy eyes. The effects of lutein/zeaxanthin intake at doses <5 mg/d or from dietary sources is less clear. Increased lutein/zeaxanthin intake can help with maintaining ocular health. Future research is needed to determine the minimum dose and duration of lutein/zeaxanthin intake that is associated with a clinically important change in MPOD or visual function.
... Diet, as a modifiable environmental factor, plays an important role in modulating psychological stress and preventing stress-related disease [41]. In general support of this idea, there have been recent human and animal studies reporting stress-reducing effects of specific nutrients, or dietary patterns [42]. In animal experiments, calorie restriction, Mediterranean diet, and diets containing prebiotics and/or glycoprotein lactoferrin were proven to reduce psychological stress or enhance stress resilience [43][44][45]. ...
... In animal experiments, calorie restriction, Mediterranean diet, and diets containing prebiotics and/or glycoprotein lactoferrin were proven to reduce psychological stress or enhance stress resilience [43][44][45]. Regarding human research, dietary supplementation with specific nutrients, such as macular carotenoids [42], omega-3 [46], omega-6 [46], Eicosatetraenoic-Acid-enriched phospholipids [47], bioactive components [48], probiotics [49] and B group vitamins [50], was found to reduce psychological distress and mental-disease symptoms, through mechanisms possibly related to neuroinflammation and apoptosis [47]. Moreover, diet pattern was reported to influence psychological distress and stress-induced disorders. ...
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Specific nutrients or dietary patterns influence an individual’s psychological stress. As a major aspect of a healthy diet, the influence of dietary diversity on psychological stress remains uncertain. Within these contexts, we aimed to examine the association between the dietary diversity score and psychological stress, using prospective data from the China Health and Nutrition Survey (CHNS). We included 7434 adult participants, with complete dietary information, in the 2011 wave, and followed-up with perceived stress scale (PSS-14) in the 2015 wave. The dietary intake of foods was coded into 29 food groups, using the DQQ for China, and the dietary diversity scores were obtained, using DQQ, by calculating the number of food groups consumed during one 24-h dietary recall. The univariate analysis, and logistic regression model were used to examine the relationship between psychological stress and diet diversity. Approximately half of the participants (4204, 56.55%) perceived a higher level of stress (PSS-14 total score > 25). Dietary diversity was lower in the higher-stress group (p for trend <0.0001). Unconditional multivariate logistic regression demonstrated that participants with higher daily dietary diversity were less likely to experience higher-level psychological stress, compared with participants with lower daily dietary diversity (ORs range: 0.480–0.809). Dietary diversity was found to be inversely associated with psychological stress, in this prospective analysis of a national population. Further studies are required to figure out the mechanism and effectiveness of dietary diversity on psychological stress.
... Carotenoids have also shown beneficial effects in the management of stress [43,45]. Kell et al. evaluated the therapeutic benefits of saffron, particularly the crocin (carotenoid) it contains, in the management of mood, stress, and anxiety disorders [45]. ...
... After 4 weeks of treatment with 28 mg/day of saffron, subjects saw their stress and anxiety levels decrease and their mood improve significantly compared with placebo. Another study conducted by Stringham et al. sought to demonstrate the value of long-term carotenoid supplementation in the management of stress [43]. Carotenoids or placebo were administered for 12 months and the level of stress associated with cortisol levels was assessed. ...
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Phytonutrients comprise many different chemicals, including carotenoids, indoles, glucosinolates, organosulfur compounds, phytosterols, polyphenols, and saponins. This review focuses on the human healthcare benefits of seven phytochemical families and highlights the significant potential contribution of phytonutrients in the prevention and management of pathologies and symptoms in the field of family health. The structure and function of these phytochemical families and their dietary sources are presented, along with an overview of their potential activities across different health and therapeutic targets. This evaluation has enabled complementary effects of the different families of phytonutrients in the same area of health to be recognized.
... The relationship of plasma concentrations of cortisol and DHEA has been proposed when elevated, as a marker of morbidity and mortality [53]. In fact, lifestyle strategies that can reduce the first and increase the second hormone, such as physical exercise [54,55] or dietary supplementation [56,57], have been proposed as suitable for a better health maintenance. In the present study, sleeping for two months in the HOGO bed decreases significantly the cortisol/ DHEA ratio thus playing in the right direction. ...
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Background The electromagnetic fields (EMFs) emitted by the technologies affect the homeostatic systems (nervous, endocrine, and immune systems) and consequently the health. In a previous work, we observed that men and women, after 2 months of using a bed with a registered HOGO system, that prevents and drain EMFs, improved their immunity, redox and inflammatory states and rejuvenated their rate of aging or biological age. Since, EMFs can act as a chronic stressor stimulus, and affect the sleep quality. The objective of this work was to study in men and women (23–73 years old) the effect of sleeping for 2 months on that bed in the blood concentrations of several hormones related to stress response and sleep quality as well as to corroborate the rejuvenation of their biological age. Methods In 18 men and women, plasma concentration of cortisol, dehydroepiandrosterone (DHEA), catecholamines (epinephrine, norepinephrine and dopamine), serotonin, oxytocin and melatonin were analyzed before and after 2 months of using the HOGO beds. A group of 10 people was used as placebo control. In another cohort of 25 men (20 experimental and 5 placebo), the effects of rest on the HOGO system on the concentration of cortisol and testosterone in plasma were studied. In all these volunteers, the biological age was analyzed using the Immunity Clock model. Results There is a significant increase in plasma concentration of DHEA, norepinephrine, serotonin, oxytocin, and melatonin as well as in testosterone, after resting for 2 months in that bed with the EMFs avoiding system. In addition, decreases in Cortisol/DHEA and Testosterone/cortisol ratio and plasma dopamine concentration were observed. No differences were found in placebo groups. In all participants that slept on HOGO beds, the biological age was reduced. Conclusions Sleeping in a bed that isolates from EMFs and drain them can be a possible strategy to improve the secretion of hormones related to a better response to stress and sleep quality, which means a better endocrine system, and consequently better homeostasis and maintenance of health. This fact was confirmed with the slowdown in the rate of aging checked with a rejuvenation of the biological age.
... In green leaves and leafy vegetables which contain higher amounts of chlorophyll, the color of carotenoids is masked despite its significant content [64]. Due to their antioxidant properties, carotenoids have been associated with the prevention of several types of cancer development [65], cardiovascular and neurodegenerative diseases [66], chronic psychological stress [67], inflammation, as well as macular degeneration [68][69][70][71]. ...
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The present study was carried out to evaluate and compare in vitro antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC), and ferric reducing antioxidant power (FRAP)), antimicrobial, anticancer activities, and the individual carotenoids and anthocyanins content of methanol extracts of the Cyclamen genotypes: Persian cyclamen accessions (Cyclamen persicum Mill.), sowbread (C. mirabile Hildebr.), and ivy-leaved cyclamen (C. hederifolium Mill.) aerial parts. The HPLC-PDA analysis revealed the presence of five individual carotenoids (i.e., neoxanthin, violaxanthin, lutein, β-carotene, and cis-β-carotene) as the main compounds in Cyclamen leaves, and the presence of seven individual anthocycanins (i.e., cyanidin 3,5-di-O-glucoside, peonidin-rutinoside, peonidin 3,5-di-O-glucoside, peonidin 3-O-glucoside, malvidin 3-O-glucoside, malvidin 3,5-di-O-glucoside, and malvidin-rutinoside) in Cyclamen flowers reported, hereby, for the first time. The highest phenolic content was found in the leaves of LC6, C. mirabile (46.32 ± 0.14 mg/g gallic acid equivalents [GAE]), and in the flowers of C. persicum Merengue Magenta (FC15) (58.63 ± 0.17 mg/g GAE), whereas the highest flavonoid content was reported in C. persicum Halios Falbala leaves, namely LC9 (54.90 ± 0.27 mg/g quercetin equivalents [QE]) and in flowers of C. persicum Victora (FC2) (77.87 ± 0.25 mg/g QE). The highest antioxidant activity in DPPH and FRAP assays was reported in C. persicum Dark Violet (LC1) and Victoria (LC2), whereas C. mirabile (LC6) had the highest activity in the TEAC assay. In flowers, high antioxidant activities in DPPH and TEAC were noticed in C. persicum Superserie Red (FC7) and Dark Violet (FC1), respectively, and Halios Falbala (FC9) exhibited the highest activity in the TEAC assay. Additionally, FC9 exhibited the highest antibacterial activity in almost all tested bacteria compared with the leaves extracts. Furthermore, the highest in vitro citotoxicity in MDA-MB-231 cells was noticed in C. hederifolium LC18 (56.71–69.35%) and FC18 (40.07–41.43%), with a lower effect against BJ cells demonstrating selective toxicity. The above findings, highlight the potential use of the Cyclamen flower and leaf extracts as significant anticancer agents along with their antioxidant and antimicrobial properties.
... Lutein and zeaxanthin are also found in the macula of the human eye, which is a cluster of cones responsible for color (daytime) vision [36]. In addition to research on the protective effect of lutein and zeaxanthin on eye structures, previous scientific reports have indicated that supplementation with carotenoid pigments improves cognitive functions, reduces the level of cortisol and stress symptoms in young and adult people, and induces antioxidant effects [36][37][38]. ...
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Cordyceps spp. mushrooms have a long tradition of use as a natural raw material in Asian ethnomedicine because of their adaptogenic, tonic effects and their ability to reduce fatigue and stimulate the immune system in humans. This review aims to present the chemical composition and medicinal properties of Cordyceps militaris fruiting bodies and mycelium, as well as mycelium from in vitro cultures. The analytical results of the composition of C. militaris grown in culture media show the bioactive components such as cordycepin, polysaccharides, -aminobutyric acid (GABA), ergothioneine and others described in the review. To summarize, based on the presence of several bioactive compounds that contribute to biological activity, C. militaris mushrooms definitely deserve to be considered as functional foods and also have great potential for medicinal use. Recent scientific reports indicate the potential of cordycepin in antiviral activity, particularly against COVID-19.
... Provitamin A and non-provitamin A pigments present other equally relevant biological activities. In this sense, carotenoids were recently associated to the improvement in health conditions such as ocular diseases (Giannaccare et al., 2020), cardiovascular disease (Petyaev et al., 2018), fatty liver disease (Gao et al., 2019), cancer (Gong, Smith, Swanson, & Rubin, 2018), liver fibrosis (Algandaby, 2018), chronic psychological stress (Stringham, Holmes, & Stringham, 2018) and neurodegenerative diseases (Cho, Shin, Kim, & Lee, 2018). ...
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Carotenoids are natural pigments that present several bioactive properties, including antioxidant, anticarcinogenic and provitamin A activities. However, these compounds are susceptible to degradation when exposed to a number of conditions (e.g. light, heat, oxygen), leading to loss of benefits and hampering their application in food products. Their hydrophobicity also makes incorporation into water-based foods more difficult. Microencapsulation techniques have been applied for decades to provide stability to carotenoid-rich extracts under typical conditions of processing and storage of foods, besides offering several other advantages to the use and application of these materials. This work reviews the recent advances in the microencapsulation of carotenoid-rich extracts, oils and oleoresins from varying sources, evidencing the technologies applied to encapsulate these materials, the effects of encapsulation on the obtained particles, and the impact of such processes on the bioaccessibility and release profile of carotenoids from microparticles. Moreover, recent applications of carotenoid-rich microparticles in food products are discussed. Most of the applied processes were effective in improving different aspects of the encapsulated materials, especially the stability of carotenoids during storage, resulting in microparticles with promising properties for future applications in food products. However, the lack of information about the effects of microencapsulation on carotenoids during processing of model foods, the sensory acceptance of enriched food products and the bioaccessibility and bioavailability of microencapsulated carotenoids reveals gaps that should be explored in the future.
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Background New research supports an integrated approach to treating depression, and lifestyle modifications should be a regular component of both preventative and treatment programs. Therefore, in order to investigate the relationship between various antioxidant supplements and depressive status, we carried out a meta-analysis of randomized controlled trials (RCT). Methods We thoroughly searched PubMed, Medline, Scopus, and Web of Science databases to screen publications focusing on the effects of antioxidant supplements on depression status. The meta-analysis mainly compared depression scores between groups that received antioxidant supplements and controls. We also pooled studies reporting changes in anxiety status as a secondary outcome. Results 52 studies with 4049 participants were eventually identified. The meta-analysis found that the positive effect of antioxidant supplementation, such as magnesium (SMD = 0.16, p = 0.03), zinc (SMD = 0.59, p = 0.01), selenium (SMD = 0.33, p = 0.009), CoQ10 (SMD = 0.97, p = 0.05), tea and coffee (SMD = 1.15, p = 0.001) and crocin (MD = 6.04, p < 0.00001), on depressive status were all significant. And antioxidant supplementation also showed significant improvement in anxiety (SMD = 0.40, p < 0.00001). Subgroup analysis by scale types and countries were performed, and antioxidant supplementation's positive effects on depressive and anxiety states remained significant. Limitations This study did not limit the characteristics of the included population, and the diversity of scales also contributed to the heterogeneity. Conclusion Intake of antioxidant supplements is associated with improved depression and anxiety states, further affirms the therapeutic potential of antioxidant supplements as adjunctive therapy to conventional antidepressants.
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The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease.
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Oxidative stress has gained attention recently in behavioral medicine and has been reported to be associated with various psychological disturbances and their prognoses. Study aims to evaluate the oxidative stress (malonylaldehyde (MDA) levels) and its relation with psychological factors (dimensions of personality, levels of anxiety, stress, and depression) among medical/paramedical students of 1(st) and 3(rd) year). A total of 150 students; 75 from 1(st) year (2010-2011) and75 from 3(rd) year (2009-2010); of medical and paramedical background were assessed on level of MDA (oxidative stress) and personality variables, that is, level of anxiety, stress, and depression. These psychological variables were correlated with the level of their oxidative stress. Findings revealed that both groups are influenced by oxidative stress and their psychological variables are also compatible in order to confirm their vulnerabilities to stress. Stress in 3(rd) year students was significantly higher and it was noted that it adversely affects the psychological parameters. Hence, special attention on mental health aspect in these students may be given.
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Abstract Suboptimal health status (SHS) has become a new public health challenge in China. This study investigated whether high SHS is associated with psychosocial stress, changes in cortisol level and/or glucocorticoid receptor (GR) isoform expression. Three hundred and eighty-six workers employed in three companies in Beijing were recruited. The SHS score was derived from data collection in the SHS questionnaire (SHSQ-25). The short standard version of the Copenhagen Psychosocial Questionnaire (COPSOQ) was used to assess job-related psychosocial stress. The mean value of the five scales of COPSOQ and distribution of plasma cortisol and mRNA expression of GRα/GRβ between the high level of SHS group and the low level of SHS group were compared using a general linear model procedure. Multiple linear regression analysis was used to analyze the effect of psychosocial stress on SHS. We identified three factors which were predictive of SHS, including 'demands at work', 'interpersonal relations and leadership' and 'insecurity at work'. Significantly higher levels of plasma cortisol and GRβ/GRα mRNA ratio were observed among the high SHS group. High level of SHS is associated with decreased mRNA expression of GRα. The present study confirmed the association between chronic psychosocial stress and SHS, indicating that improving the psychosocial work environment may reduce SHS and then prevent chronic diseases effectively.
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Endurance exercise induces IL-6 production from myocytes that is thought to impair intracellular defence mechanisms. Curcumin inhibits NF-κB and activator protein 1, responsible for cytokine transcription, in cell lines. The aim of this study was to investigate the effect of curcumin supplementation on the cytokine and stress responses following 2 h of cycling. Eleven male recreational athletes (35.5 ± 5.7 years; Wmax 275 ± 6 W; 87.2 ± 10.3 kg) consuming a low carbohydrate diet of 2.3 ± 0.2 g/kg/day underwent three double blind trials with curcumin supplementation, placebo supplementation, and no supplementation (control) to observe the response of serum interleukins (IL-6, IL1-RA, IL-10), cortisol, c-reactive protein (CRP), and subjective assessment of training stress. Exercise was set at 95% lactate threshold (54 ± 7% Wmax) to ensure that all athletes completed the trial protocol. The trial protocol elicted a rise in IL-6 and IL1-RA, but not IL-10. The supplementation regimen failed to produce statistically significant results when compared to placebo and control. IL-6 serum concentrations one hour following exercise were (Median (IQR): 2.0 (1.8-3.6) Curcumin; 4.8 (2.1-7.3) Placebo; 3.5 (1.9-7.7) Control). Differences between supplementation and placebo failed to reach statistical significance (p = 0.18) with the median test. Repeated measures ANOVA time-trial interaction was at p = 0.06 between curcumin supplementation and placebo. A positive correlation (p = 0.02) between absolute exercise intensity and 1 h post-exercise for IL-6 concentration was observed. Participants reported "better than usual" scores in the subjective assessment of psychological stress when supplementing with curcumin, indicating that they felt less stressed during training days (p = 0.04) compared to placebo even though there was no difference in RPE during any of the training days or trials. The limitations of the current regimen and trial involved a number of factors including sample size, mode of exercise, intensity of exercise, and dose of curcumin. Nevertheless these results provide insight for future studies with larger samples, and multiple curcumin dosages to investigate if different curcumin regimens can lead to statistically different interleukin levels when compared to a control and placebo.
Stress is common for all organisms either in the form of eustress (beneficial) or as distress (harmful). Stress is highly diverse in present world and its effects in organisms are well studied. This study is a comparative effect of stress in the generation of reactive oxygen species in albino Wistar rats, which are seldom reported. Here animals were grouped into four and the test animals of each group were administered with any one of the following stress, namely forced swimming induced stress (FS), and noise induced stress (NS), immobilization stress (IS) and overcrowding stress (OS). After stress administration, serum cortisol was estimated as a bio marker of stress in the albino rats, and the liver homogenate were used to estimate superoxide dismutase (SOD) by using rat Elisa kit in the spectrophotometer. The data were processed with unpaired 't' test. The cortisol levels were found to be increased in a highly significant level (P < 0.001) in all the groups as compared to the normal control. And the stress level was found to be maximum in the FS group in comparison with other groups. The mean cortisol level in different stress groups such as FS, NS, IS and OS were found to be 4.15, 3.7, 3.63, 3.62 μ gm/dl respectively. Among all the stressed groups, the SOD level in the FS group were found to be increased in a highly significant level (P < 0.001) in comparison with normal control group. The SOD level in FS group was (30.75 U/mgm. protein) followed by OS (28.96), noise (28.88) and IS (28.77).
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The difficulties inherent in obtaining consistent and adequate diagnoses for the purposes of research and therapy have been pointed out by a number of authors. Pasamanick12 in a recent article viewed the low interclinician agreement on diagnosis as an indictment of the present state of psychiatry and called for "the development of objective, measurable and verifiable criteria of classification based not on personal or parochial considerations, but on behavioral and other objectively measurable manifestations."Attempts by other investigators to subject clinical observations and judgments to objective measurement have resulted in a wide variety of psychiatric rating scales.4,15 These have been well summarized in a review article by Lorr11 on "Rating Scales and Check Lists for the Evaluation of Psychopathology." In the area of psychological testing, a variety of paper-and-pencil tests have been devised for the purpose of measuring specific