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Short-Term Study on the Effects of Rosemary on Cognitive Function in an Elderly Population

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Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify investigation for a potential role in reducing widespread cognitive decline in the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures crossover study was conducted to investigate possible acute effects of dried rosemary leaf powder on cognitive performance. Twenty-eight older adults (mean age, 75 years) were tested using the Cognitive Drug Research computerized assessment system 1, 2.5, 4, and 6 hours following a placebo and four different doses of rosemary. Doses were counterbalanced, and there was a 7-day washout between visits. There was a biphasic dose-dependent effect in measures of speed of memory: the lowest dose (750 mg) of rosemary had a statistically significant beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000 mg) had a significant impairing effect (P<.01). There were significant deleterious effects on other measures of cognitive performance, although these were less consistent. Speed of memory is a potentially useful predictor of cognitive function during aging. The positive effect of the dose nearest normal culinary consumption points to the value of further work on effects of low doses over the longer term.
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Short-Term Study on the Effects of Rosemary on Cognitive Function
in an Elderly Population
Andrew Pengelly,
1
James Snow,
1
Simon Y. Mills,
1
Andrew Scholey,
2
Keith Wesnes,
2,3
and Leah Reeves Butler
1
1
Herbal Medicine Department, Tai Sophia Institute, Laurel, Maryland, USA.
2
NICM Centre for Neurocognition, Brain Sciences Institute, Swinburne University, Melbourne, Victoria, Australia.
3
United BioSource Corporation, Goring-on-Thames, United Kingdom.
ABSTRACT Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify investigation for a potential role in
reducing widespread cognitive decline in the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures cross-
over study was conducted to investigate possible acute effects of dried rosemary leaf powder on cognitive performance. Twenty-eight
older adults (mean age, 75 years) were tested using the Cognitive Drug Research computerized assessment system 1, 2.5, 4, and 6
hours following a placebo and four different doses of rosemary. Doses were counterbalanced, and there was a 7-day washout between
visits. There was a biphasic dose-dependent effect in measures of speed of memory: the lowest dose (750 mg) of rosemary had a
statistically significant beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000 mg) had a significant
impairing effect (P<.01). There were significant deleterious effects on other measures of cognitive performance, although these were
less consistent. Speed of memory is a potentially useful predictor of cognitive function during aging. The positive effect of the dose
nearest normal culinary consumption points to the value of further work on effects of low doses over the longer term.
KEY WORDS: acute effects clinical trial cognitive memory rosemary Rosmarinus
INTRODUCTION
Reduced cognitive faculties are a frequent conse-
quence of aging and a major threat to quality of life.
Anticholinesterase and other drug treatments are available
for cognitive decline;
1
however, their potential cognitive
benefits are not necessarily apparent in older subjects,
and some such drugs have been shown to promote nega-
tive neurocognitive effects in this age group.
1,2
Traditional plant-based remedies have long-standing
reputations for supporting healthy aging, and recent inves-
tigations have examined the potential for cognitive en-
hancement of such medicines.
3–9
A recent meta-analysis of
13 randomized controlled trials into herbal interventions for
dementia concluded that herbal medicines were more ef-
fective than placebo and at least equivalent to conventional
therapies on common cognitive performance outcome
measures.
10
Additional studies have focused on cognitive
changes brought about by herbal intervention in healthy older
adults (e.g., for Bacopa monnieri,
11
Ginkgo biloba,
12–14
Centella asiatica,
15
and cranberry juice
16
). Several investi-
gations have been conducted into members of the mint
family (Lamiaceae),
17
including lemon balm (Melissa offi-
cinalis),
18,19
sage (Salvia officinalis,Salvia lavandulaefo-
lia),
20–22
lavender (Lavandula angustifolia),
23
and rosemary
(Rosmarinus officinalis).
23
Rosemary (R. officinalis L., Family Lamiaceae) is native
to the Mediterranean region, where the ancient Greeks re-
vered it for stimulating the brain and assisting memory;
24
Dioscorides wrote of rosemary: ‘‘the eating of its flower in a
preserve comforts the brain, the heart and the stomach;
sharpens understanding, restores lost memory, awakens the
mind, and in sum is a healthy remedy for various cold ail-
ments of the head and the stomach.’’ Rosemary has Gen-
erally Recognized as Safe status in the United States and is
widely used as a culinary herb. Extracts of rosemary and its
dried leaf are also available as ‘‘dietary supplements.’
Rosemary contains an essential oil (0.6–2%) of varying
composition (three main chemotypes are found growing in
Europe). The major constituents of the essential oil are 1,8-
cineole, a-pinene, camphor, borneol, and carvacrol, but the
exact composition can vary between individual samples and
time of harvest.
25–27
Other constituents include phenolic
diterpenes, flavones, the caffeic acid derivative rosmarinic
acid, and the triterpene ursolic acid.
28,29
In experimental studies, rosemary extracts were shown to
possess potent radical scavenging activity.
26,30
The di-
terpenes carnosol and carnosic acid are thought to be the
major antioxidant components,
26,27
although antioxidant
properties have also been reported for several other
Manuscript received 7 January 2011. Revision accepted 15 June 2011.
Address correspondence to: Andrew Pengelly, Herbal Medicine Department, Tai Sophia
Institute, 7750 Montpelier Road, Laurel, MD 20723, USA, E-mail: apengelly@tai.edu
JOURNAL OF MEDICINAL FOOD
J Med Food 15 (1) 2012, 10–17
#Mary Ann Liebert, Inc. and Korean Society of Food Science and Nutrition
DOI: 10.1089/jmf.2011.0005
10
constituents, including rosmarinic acid.
31–34
In vitro studies
with rosemary extracts have demonstrated acetylcholines-
terase inhibition,
8,35
butyrylcholinesterase inhibition,
36
and
a protective effect on dopaminergic neurons.
37
Using mouse models an antidepressant effect of rosemary
has been identified, apparently mediated by an interaction
with the monoaminergic system.
38
There are antinociceptive
effects in animals
39
inhibited by naloxone pretreatment
40
suggesting interaction with the endogenous endorphin system,
as well as antispasmodic effects on tracheal smooth muscle.
41
There are few clinical studies on the effects of rosemary.
In a randomized study of 140 healthy young adults, inha-
lation of rosemary oil enhanced feeling of alertness and
cognitive functions as evaluated using the Cognitive Drug
Research (CDR) test battery used in the current study.
22
In a
separate study the aroma of rosemary oil increased perfor-
mance in exam students while increasing free radical
scavenging activity and reducing cortisol levels.
42
However,
to date there are no clinical studies on cognitive perfor-
mance following ingestion of rosemary.
MATERIALS AND METHODS
The current study was a randomized, placebo-controlled,
double-blinded, repeated-measures, crossover study inves-
tigating acute effects of dried rosemary (R. officinalis L.)
leaves on cognitive performance in older adults, using a
battery of tests provided by the CDR.
43
Because the acute
effects of rosemary were being explored, doses higher than
normally consumed in the diet were applied. Additionally,
the crude rosemary powder was used in a dietary formula-
tion rather than a pharmaceutical extract to retain the
pharmacokinetic profile of ordinary culinary consumption.
Subjects
Twenty-eight subjects (eight men, 20 women) were re-
cruited via local media and networking. They were non-
smokers between 65 and 90 years (mean, 75 years) in a stable
state of health with no confounding medications and able to
complete the computerized battery tests on laptop computers.
Ethical approval was obtained from the Institutional Review
Board of Tai Sophia Institute (Laurel, MD, USA). This study
complied with current guidelines for Good Clinical Practice
guidance issued by the U.S. Food and Drug Administration to
protect human subjects of research and the Ethical Principles
for Medical Research Involving Human Subjects adopted in
the World Medical Association Declaration of Helsinki.
Treatments
The test substance consisted of 100% powdered rosemary
(R. officinalis L.) originating from Turkey and supplied by
McCormick & Co. (Hunt Valley, MD, USA). Authentication
was performed by Dr. Arthur Tucker at Delaware State Uni-
versity (Dover, DE, USA) based on macro- and microscopic
features. Seven constituents were characterized and quantified
applying gas chromatographic and mass spectrometric meth-
ods modified from those of Razbors
ˇek et al.
44
Hydrodistillation
of the rosemary sample yielded 1.4% volatile oil, consisting of
1,8-cineole (0.57%), borneol (0.14%), and a-pinene (0.13%) as
the major components. In addition, key nonvolatile compounds
were quantified, including rosmarinic acid (1.45% wt/wt),
carnosic acid (1.73%), and ursolic acid (2.89%).
The powdered rosemary was added to a commercial to-
mato juice (Campbell’s [Camden, NJ, USA] low sodium).
Subjects on each study day received a single 16-ounce
(458-mL) drink of reduced sodium tomato juice containing
(in decreasing order of weight) water, tomato concentrate,
potassium chloride, vitamin C (ascorbic acid), citric acid, salt,
flavoring, and malic acid. Total oxygen radical absorbance
capacity per serving was calculated as 10,782 lmol of Trolox
equivalents, and the content of total phenolics was 299 mg of
gallic acid equivalents. Each 458 mL of juice additionally
contained one of the following doses of rosemary: (1) no
rosemary (placebo; see below); (2) 750mg of dried rosemary;
(3) 1,500mg of dried rosemary; (4) 3,000 mg of dried rose-
mary; or (5) 6,000 mg of dried rosemary. A third party pre-
pared, codified, and delivered the treatments to participants.
Masking was achieved by the use of opaque containers with
black drinking straws and by chilling the drink.
Placebo consisted of the tomato juice as described above.
To confound distinction further between the treated and
untreated tomato juice, each dose was co-administered with
colored methylcellulose-filled capsules. Subjects were in-
formed that these capsules could be part of the treatment.
Cognitive measures
A battery of tasks from the CDR System was adminis-
tered. Parallel forms of the tasks were performed at different
sessions to reduce practice effect on repeated assessment.
The information in all tasks was presented on the screen of a
notebook computer, and with the exception of the written
word recall tasks the responses were recorded via a response
module containing ‘‘NO’’ and ‘‘YES’’ buttons. The battery
took about 25 minutes to perform (Table 1 contains brief
descriptions [see, for example, Tildesley et al.
20
for de-
tails]). The individual task outcomes from the battery were
collapsed into five cognitive ‘‘factors,’’ as recommended by
CDR following their derivation by factor analysis
43
(Fig. 1).
Two of these factors concern attention: ‘‘power of atten-
tion’’ (sometimes called ‘‘speed of attention’’) reflects the
ability to focus attention, whereas continuity of attention (or
‘‘accuracy of attention’’) reflects the ability to sustain at-
tention. ‘‘Quality of working memory’’ reflects the ability to
successfully hold numeric and spatial information tempo-
rarily in working memory, whereas ‘‘quality of episodic
memory’’ reflects the ability to store, hold, and subsequently
retrieve verbal and non-verbal information in long-term
(episodic) memory. ‘‘Speed of memory’’ reflects the time
taken to successfully retrieve information from both work-
ing and episodic memory.
Mood measures
Mood was assessed using the Bond–Lader visual analog
scales.
45
These consist of 16 100-mm lines anchored by
ROSEMARY COGNITION STUDY 11
antonyms (e.g., ‘‘clearheaded–muzzy’’), which are com-
bined to derive three mood factors of alert, calm, and con-
tent. The Bond–Lader Visual Analogue Scales were
presented by computer.
Procedure
The tests were performed under experimenter supervision
on five separate 1-day treatment sessions every week for 5
weeks following a practice day. The order of intervention on
the five study visits was determined by random allocation.
Each study day comprised five identical testing sessions: a
pre-dose testing session to establish baseline performance
for that day, followed immediately by the allocated inter-
vention and assessments at 1, 2.5, 4, and 6 hours following
consumption. Subjects were asked to refrain from alcohol at
least 12 hours prior to assessments on these days.
Data treatment and statistics
Changes from baseline scores for the treatments were
computed for each cognitive measure, at each time point.
These data were subjected to a general linear mixed-model
analysis of covariance with terms fitted to the model for
treatment (6,000 mg, 3,000 mg, 1,500 mg, 750 mg, 0 mg),
day (Day 1, Day 2, Day 3, Day 4, and Day 5), visit (diff 1,
diff 2, diff 4, diff 6), treatment ·visit, and participant. A
‘‘repeated-measures’’ analysis of covariance was conducted
using SAS PROC MIXED (SAS Institute, Cary, NC, USA).
Using the baseline on each study day as a covariate allowed
control for differences between subjects. Statistical signifi-
cance was set at a value of P<.05, whereas P<.01 was set
as highly significant.
RESULTS
Of the total 28 participants who began the study, one was
asked to leave because of concerns about a preexisting
medical condition. There were no other dropouts.
There was a main effect of treatment for ‘‘speed of
memory’’ measures (F
4,96
=7.19, P<.0001) that was dose-
specific. At 750 mg there was a significant improvement
(P=.01), and at 6,000 mg there was a significant impairment
(P<.01), compared with placebo. All treatments including
placebo showed a significant impairment compared with
baseline except the 750-mg dose, which showed negligible
difference from baseline.
‘‘Continuity of attention’’ was significantly impaired at
1,500 (P<.001), 3,000 (P=.04), and 6,000 mg (P<.001)
doses, and ‘‘quality of working memory’’ was significantly
impaired at 750 (P=.02), 1,500 (P=.01), and 6,000 mg
(P=.01), in both cases compared with placebo. However, the
differences are much smaller when compared with baseline.
There were no effects for the ‘‘power of attention’’ and
‘‘quality of episodic secondary memory’’ scores (Fig. 2 and
Table 2).
For the self-ratings of mood and alertness, all scores in-
cluding placebo were reduced from baseline as the testing
day progressed. Of note was a significant improvement at
Table 1. Cognitive Drug Research Tests
Tests were administered in the following order:
Word Presentation: A list of words is presented for the subject to remember.
Immediate Word Recall: Immediately after the last word is presented, the subject is given 1 minute to write as many of the words as
possible on a sheet of paper.
Picture Presentation: A series of pictures for the subject to remember is presented.
Simple Reaction Time: The subject is instructed to press the ‘‘YES’’ response button, as quickly as possible, every time the word ‘‘YES’
is presented.
Digit Vigilance: A target digit is pseudo-randomly selected and constantly displayed to the right of the screen. A series of digits is then
presented in the center of the screen. The subject is required to press the ‘‘YES’’ button as quickly as possible every time a digit in the
series matches the target digit.
Choice Reaction Time: The subject is required to respond to the words ‘‘YES’’ and ‘‘NO’’ as they appear by pressing the corresponding
button as quickly as possible.
Spatial Working Memory: A picture of a house is presented on the screen with four of the nine windows lit. The subject is asked to memorize
the position of the lit windows. For each of the subsequent presentations of the house, the subject is asked to decide whether or not the
single window that is lit had been lit in the original presentation. The subject responds by pressing the corresponding ‘‘YES’’ or ‘‘NO’’
button, as appropriate, as quickly as possible.
Numeric Working Memory: A series of digits is presented for the subject to hold in memory. This is followed by a series of probe digits,
for each of which the subject has to decide whether it had appeared in the original series and press the corresponding ‘‘YES’’ or ‘‘NO’
response button as quickly as possible.
Delayed Word Recall: The subject is again given 1 minute to write as many of the words as possible in any order on a sheet of paper.
Word Recognition: The original words from Word Presentation plus distractor words are presented, one at a time, in a randomized order. For
each word, the subject is required to indicate whether he or she recognizes it from the original list of words by pressing the corresponding
‘‘YES’’ or ‘‘NO’’ button as quickly as possible.
Picture Recognition: The original pictures from Picture Presentation plus distractor pictures are presented, one at a time. For each picture,
the subject is required to indicate whether he or she recognizes it from the original series by pressing the corresponding ‘‘YES’’ or ‘‘NO’
button as quickly as possible.
Bond-Lader Visual Analogue Scales of Mood and Alertness: For this computerized questionnaire scale, the subject is required to rate
how he or she feels ‘‘at this moment.’’
45
12 PENGELLY ET AL.
FIG. 1. Derivation of cognitive fac-
tors from the Cognitive Drug Research
battery outcomes.
FIG. 2. Effects of R. officinalis (rose-
mary [RO]) powder (750, 1,500, 3,000,
and 6,000 mg) and placebo on cogni-
tive factors derived from Cognitive
Drug Research battery scores. Mean
changes from baseline are shown for
(a) power of attention, (b) continuity
of attention, (c) speed of memory, (d)
working memory, and (e) secondary
memory.
13
750 mg in alertness (P=.01) compared with placebo,
whereas at 6,000 mg there was the opposite effect indicating
decreased alertness compared with placebo (P=.02). This
finding suggests a biphasic dose–response curve similar to
that observed for the speed of memory factor (Table 3).
The mixed analysis of covariance showed there was no
correlation between treatment and time in any of these
findings. A further analysis was carried out to explore
whether there was any global order effect. Some orders were
identified, but the counterbalancing ensured they did not
contribute to the study results.
There were no serious adverse events recorded in placebo
or treatment groups during the study.
DISCUSSION
This study clearly demonstrates significant dose-specific
effects of rosemary on ‘‘speed of memory’’ compared with
placebo: positive for the lowest dose (750 mg) but negative
at the highest dose tested (6,000 mg). Moreover, when
compared with baseline the 750-mg dose appears to counter
the impairments that occur under placebo, possibly due to
fatigue. The fact that subjects at this dose subjectively re-
ported significantly less impairment to their alertness com-
pared with placebo strengthens the findings, particularly as
there is research suggesting that mood is an underlying
driver of cognitive function.
46
Several rosemary doses produced impairment of the
‘‘continuity of attention’’ and ‘‘quality of working memory’
factors, but none of these effects was dose specific. The
mechanisms underlying these effects are not known. How-
ever, the preparation is rich in bioactive constituents, in-
cluding the monoterpenoids a-pinene, 1,8-cineole, and
borneol. A recently characterized extract of S. officinalis
(sage) with both anticholinesterase and memory-enhancing
properties contained these same constituents.
46
Ad-
ditionally, ursolic acid, rosmarinic acid, and carnosic acid
found in rosemary are bioavailable and have characterized
physiological effects that may influence cognitive func-
tioning. The presence of multiple potentially psychoactive
components is also likely to underlie the complex dose–
response relationships observed in the current study.
47,48
Quality of working memory differed from speed of mem-
ory, which is interesting in light of evidence suggesting that
decreased processing speed is responsible for impaired
working memory and skill acquisition in older adults, possibly
contributing to age-related decline in overall intelligence.
49–53
Rodrı
´guez-Sa
´nchez et al.
53
cited many reports demonstrating
links between reduced speed of processing and cognitive
dysfunction with impaired declarative or working memory in
normal aging, traumatic brain injury, depression, and Par-
kinson’s disease. There are two functional components of
human working memory: short-term working memory and
long-term working memory. Short-term working memory
involves actively updating and manipulating representations,
switching and dividing attention between tasks, selection of
relevant information, and inhibition of irrelevant informa-
tion.
54–59
Short-term working memory also encodes infor-
mation so that this can be retrieved from long-term working
memory. If encoding speed is not rapid enough, a person may
lose information and not be able to retrieve memories from
long-term working memory,
60
with a possible overall mem-
ory deficit for both short and long term and a potential decline
in overall intelligence.
51,57
If decreased processing speed is
responsible for impaired working memory, skill acquisition,
and overall cognitive performance in older adults as is re-
inforced by other research,
49–51,61
then any potential to im-
prove such processing speed warrants attention. The present
study’s finding for improvements in speed of memory at the
Table 2. Composite Scores for Effects of R. officinalis
Powder on Five Cognitive Factors
Cognitive factor Dose Composite score* SE Pvalue
Power of attention
(milliseconds)
750 mg -18.493 10.650 .085
1,500 mg 3.818 10.225 .709
3,000 mg 6.902 10.917 .528
6,000 mg 3.657 10.534 .729
Continuity
of attention (score)
750 mg -1.016 0.643 .117
1,500 mg -2.230 0.618 <.001
3,000 mg -1.376 0.658 .039
6,000 mg -2.363 0.637 <.001
Speed of memory
(milliseconds)
750 mg -231.920 91.204 .012
1,500 mg -96.826 87.592 .271
3,000 mg 29.130 93.453 .755
6,000 mg 253.830 91.390 .006
Quality of working
memory (score)
750 mg -0.157 0.065 .018
1,500 mg -0.167 0.063 .009
3,000 mg -0.098 0.067 .144
6,000 mg -0.169 0.065 .011
Quality of episodic
memory (score)
750 mg 1.998 6.271 .750
1,500 mg -9.140 5.992 .131
3,000 mg -8.567 6.240 .174
6,000 mg -1.695 5.928 .775
Means averaged across time points are presented with SEs and Pvalues
associated with main effects of treatment.
*All scores are differences from placebo.
Table 3. Acute Cognitive Effects of R. officinalis
Powder on Bond–Lader Mood Scale Factor Scores
Measure Dose Score SE Pvalue
Alert 750 mg 4.061 1.619 .014
1,500 mg 0.017 1.553 .991
3,000 mg -2.018 1.66 .227
6,000 mg -3.689 1.574 .021
Content 750 mg 1.267 1.238 .309
1,500 mg 1.525 1.878 .202
3,000 mg 0.546 1.269 .668
6,000 mg -0.294 1.204 .807
Calm 750 mg 2.779 2.207 .211
1,500 mg 1.761 2.118 .408
3,000 mg 2.499 2.262 .272
6,000 mg 3.553 2.149 .105
The values represent mean change from placebo for each treatment.
14 PENGELLY ET AL.
750-mg dosage merits further investigation at this and lower
dosage levels.
Limitations of the study
The activity of the placebo dose is notable in all the re-
sults. The tomato juice vehicle was chosen as a means of
delivering relatively high doses of crude rosemary powder in
culinary form. However, the results suggest the combination
of fluid consumption and constituents within the tomato juice
were unexpectedly active. There is evidence that fluid intake
may impair or improve short-term cognitive performance.
62
The population examined was not typical of the elderly
U.S. population, with education levels as well as baseline
scores on the cognitive tests above the average. When cou-
pled with the documented tendency for ‘‘participant self-
selection,’’ where volunteers in studies of this nature are
likely to be healthier, more socioeconomically advantaged,
and more highly motivated compared with their peers, the
application of the results to broader populations is reduced.
63
The short-term nature of the study does not address the
real world impact of regular consumption of rosemary. It is
not known whether regular consumption will lead to brain
adaptation or cumulative benefits. Only longer-term studies
will clarify whether regular consumption of rosemary en-
hances, diminishes, or shows no variation from the short-
term effects on cognition.
Finally, several participants were able to detect taste
differences. Subsequent analyses, however, showed no
consistent impact of this detection, and the addition of
placebo capsules to the food-based preparation may have
countered this effect.
In conclusion, rosemary powder at the dose nearest nor-
mal culinary consumption demonstrated positive effects on
speed of memory—a potentially useful predictor of cogni-
tive function during aging. The result points to the value of
future studies on effects of low doses of rosemary on
memory and cognition over the longer term.
ACKNOWLEDGMENTS
The authors are grateful to McCormick Science Institute
for their sponsorship of this study and supplying and ana-
lyzing the rosemary and for Cognitive Drug Research for the
use of their battery and materials and for data processing.
Further valuable help in analyzing the results was provided
by Dr. Charles Clark from Exeter, United Kingdom.
AUTHOR DISCLOSURE STATEMENT
K.W. is an employee of United BioSource Corporation.
A.P., J.S., S.Y.M., A.S., and L.R.B. declare no competing
financial interests exist.
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ROSEMARY COGNITION STUDY 17
... We found nine RCTs and one open-label pilot study in which the intervention antioxidantrich food was a single fruit in the form of juice [30,[47][48][49][52][53][54]56,69,70]; in three additional RCTs a reconstituted drink was used [41,46,71]; two more RCTs described the intake of a single vegetable [59,72]; and two other prospective studies used fruit and vegetable (and nuts) intake together [73] or a single beverage [74]. Finally, two more studies were focused on analyzing flavonoid intake prospectively [75] and after intervention [76]. ...
... A double-blind, repeated-measure, crossover, placebo RTC investigated the acute effects of 100% powdered rosemary (R. officinalis L.) in 28 healthy and non-smoking elderly subjects aged 65-90 years-old (mean 75 years-old) [72]. Attention, working memory, episodic memory, and "speed of memory" were evaluated at 1, 2.5, 4, and 6 h, following four different doses of rosemary, and a placebo. ...
... Carnosic acid and its oxidized form, carnosol, are considered the main antioxidants of rosemary [72]. These two phenolic diterpenes have been shown to exert neuroprotective effects in vitro on human brain cells. ...
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Oxidative stress can compromise central nervous system integrity, thereby affecting cognitive ability. Consumption of plant foods rich in antioxidants could thereby protect cognition. We systematically reviewed the literature exploring the effects of antioxidant-rich plant foods on cognition. Thirty-one studies were included: 21 intervention, 4 cross-sectional (one with a cohort in prospective observation as well), and 6 prospective studies. Subjects belonged to various age classes (young, adult, and elderly). Some subjects examined were healthy, some had mild cognitive impairment (MCI), and some others were demented. Despite the different plant foods and the cognitive assessments used, the results can be summarized as follows: 7 studies reported a significant improvement in all cognitive domains examined; 19 found significant improvements only in some cognitive areas, or only for some food subsets; and 5 showed no significant improvement or no effectiveness. The impact of dietary plant antioxidants on cognition appears promising: most of the examined studies showed associations with significant beneficial effects on cognitive functions-in some cases global or only in some specific domains. There was typically an acute, preventive, or therapeutic effect in young, adult, and elderly people, whether they were healthy, demented, or affected by MCI. Their effects, however, are not attributable only to anti-oxidation.
... In a crossover study, 28 healthy elderly individuals (65 -90 years of age) received in random order one of 4 doses of dried rosemary (750, 1,500, 3,000, or 6,000 mg) or placebo on 5 separate 1-day treatment sessions every week for 5 weeks [72]. Cognitive performance was assessed immediately after consumption and at 1, 2.5, 4, and 6 h post-consumption. ...
... Rosemary has been evaluated as an oral supplement and in aromatherapy with largely underwhelming results. Modest improvements in cognition and mood were noted in some studies, although others showed either no significant effects or negative effects on performance with elevated doses [72][73][74][75]. However, curcumin showed more promise in several studies, showing improvements in cognition and attention [83][84][85][86], while yam extract was able to improve measures of cognitive performance with more pronounced effects in older individuals [87]. ...
... In addition, many of them, e.g., caffeine, curcumin, and saffron, have a long history of culinary use and are found in plants that are known to be healthful, adding to the safety profile of longterm consumption. However, amounts greater than those used in food preparation should continue to be evaluated for safety where they are not already well-documented, e.g., rosemary in supraphysiological doses revealed negative effects on cognitive performance, but no serious adverse events were recorded [72]. ...
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Background and aim: Brain health is becoming more important to the average person as the number of people with cognitive impairments, such as Alzheimer's disease (AD), is rising significantly. The current Food and Drug Administration-approved pharmacotherapeutics for dementia neither cure nor halt cognitive decline; they just delay the worsening cognitive impairment. This narrative review summarizes the effects of nutrients and phytonutrients on cognitive function. Methods: A comprehensive literature search of PubMed was performed to find clinical trials in humans that assessed the effects of nutrients and phytonutrients on cognitive function published in English between 2000 and 2021. Six independent reviewers evaluated the articles for inclusion in this review. Results: Ninety-six articles were summarized in this narrative review. In total 21 categories of nutrients and phytonutrients were included, i.e., α-lipoic acid, Bacopa monnieri, B vitamins, cholinergic precursors, vitamin D, vitamin E, Ginkgo biloba, ginseng, lion's mane mushroom, N-acetyl cysteine, omega-3 fatty acids, aloe polysaccharides, Rhodiola rosea, rosemary, saffron, tart cherries, turmeric, wild yam, Withania somnifera, xanthines, and zinc. Particular noteworthy effects on cognition included memory, recollection, attention, intelligence, vocabulary, recognition, response inhibition, arousal, performance enhancement, planning, creative thinking, reaction time, vigilance, task switching, orientation to time, place, and person, reading, writing, comprehension, accuracy, learning, information processing speed, executive function, mental flexibility, daily functioning, decrease in mental fatigue, and freedom from distractibility. Some nutrients and phytonutrients also improved mood and contentedness and reduced anxiety and the need for caregiving. These effects are not completely consistent or ubiquitous across all patient populations or health statuses. Adverse effects were minimal or nonexistent. Conclusion: Due to the growing population of people with cognitive impairment and the lack of effective pharmacotherapeutics, it is prudent for those afflicted or their caregivers to find alternative treatments. Our narrative review shows that many of these nutrients and phytonutrients may be promising for treating some aspects of cognitive impairment, especially for people afflicted with AD. Relevance for patients: As demonstrated in a number of clinical trials, healthy adults and patients with various health challenges (e.g., AD, mild cognitive impairment, multiple sclerosis, and Parkinson's disease) exhibiting a wide range of severity in cognitive defects would be best served to consider multiple nutrients and phytonutrients to improve aspects of their cognitive function.
... Its mechanisms could be mediated by anti-inflammatory and antioxidative (Song et al., 2016). Several other studies also proved the positive effects of rosemary or its active compounds in cognitive disorders (Pengelly et al., 2012;Moss, 2017;Araki et al., 2020). ...
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Hundreds of millions of people around the world suffer from neurological disorders or have experienced them intermittently, which has significantly reduced their quality of life. The common treatments for neurological disorders are relatively expensive and may lead to a wide variety of side effects including sleep attacks, gastrointestinal side effects, blood pressure changes, etc. On the other hand, several herbal medications have attracted colossal popularity worldwide in the recent years due to their availability, affordable prices, and few side effects. Aromatic plants, sage (Salvia officinalis), lavender (Lavandula angustifolia), and rosemary (Salvia Rosmarinus) have already shown anxiolytics, anti-inflammatory, antioxidant, and neuroprotective effects. They have also shown potential in treating common neurological disorders, including Alzheimer's disease, Parkinson's disease, migraine, and cognitive disorders. This review summarizes the data on the neuroprotective potential of aromatic herbs, sage, lavender, and rosemary.
... There are also various clinical studies on the effects of R. officinalis on different aspects of memory. Pengelly et al. (62) reported that R. officinalis produced an increase in memory speed in the elderly population. Another study found that a combination of sage, R. officinalis, and lemon balm had significant effects on the improvement of verbal episodic memory in healthy people under 63 years of age (63). ...
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Patients with mild cognitive impairment eventually progress to Alzheimer's disease (AD) causing a strong impact on public health. Rosmarinus officinalis has long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aim of this review was to summarize the qualitative and quantitative aspects of R. officinalis and its active constituents in enhancing cognition. A structured search was conducted on Google Scholar and PubMed to find relevant studies that assessed the effect of R. officinalis extract or any of its active constituents on cognitive performance in animals. The following information was extracted from each study: 1) article information; 2) characteristics of study animals; 3) type of intervention: type, dose, duration, and frequency of administration of R. officinalis; and 4) type of outcome measure. Data were analyzed using Review Manager and meta-analysis was performed by computing the standardized mean difference. Twenty-three studies were selected for qualitative analysis and fifteen for meta-analysis. From the fifteen included papers, 22 with 35 comparisons were meta-analyzed. Effect sizes for intact and cognitively impaired animals were 1.19 (0.74, 1.64) and 0.57 (0.19, 0.96), indicating a positive effect on both groups. The subgroup analyses showed substantial unexplained heterogeneity among studies. Overall, R. officinalis improved cognitive outcomes in normal and impaired animals, and results were robust across species, type of extract, treatment duration, and type of memory. However, studies had a considerable amount of heterogeneity, and subgroup analyses failed to find any heterogeneity moderator.
... Moreover, a double-blind placebo-controlled human study was also performed by Pengelly et al. (2012) to determine the effects of orally-administrated rosemary powder on cognitive performance in the elderly population. Using the Cognitive Drug Research computerized assessment system test, they showed that rosemary powder in doses as low as those found in common diets (e.g., 750 mg of dried leaf powder) exhibits a significant (p \ 0.01 vs. placebo) enhancing effect on the speed of memory. ...
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Rosemary (Rosmarinus officinalis L.) of the Lamiaceae family represents an evergreen medicinal plant with various health-promoting pharmacological effects. This paper provides a complete overview of diverse biological activities of rosemary extracts, essential oils as well as their numerous bioactive compounds, ranging from antioxidative, anti-inflammatory, and antimicrobial over cognitive enhancing to their anticarcinogenic effects. In addition, state of the art extraction, distillation, fractionation, and characterization techniques for obtaining high-quality rosemary extracts and essential oils as well as methods for determining their antioxidative, antimicrobial, anti-inflammatory, and anticarcinogenic potentials are also presented. Finally, new ideas for future computational studies on chemical reactivities and binding affinities of health-promoting rosemary compounds together with suggestions for their improved bioavailability through diverse encapsulation techniques are introduced.
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Alzheimer's disease (AD) is one of the major neurodegenerative disorder. Deposition of amyloid fibrils and tau protein are associated with various pathological symptoms. Currently limited medication is available for AD treatment. Most of the drugs are basically cholinesterase inhibitors and associated with various side effects. Natural plant products have shown potential as a therapeutic agent for the treatment of AD symptoms. Variety of secondary metabolites like flavonoids, tannins, terpenoids, alkaloids and phenols are used to reduce the progression of the disease. Plant products have less or no side effect and are easily available. The present review gives a detailed account of the potential of natural plant products against the AD symptoms.
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The aim of this research was to determine yield, chemical composition and antioxidant properties of extracts and essential oils of sage (Salvia officinalis L.) and rosemary (Rosmarinus officinalis L.) leaves harvested during the months of June to September 2004. The maximum essential oil yields in the leaves were observed during July (3.24%) in sage and during August (1.35%) in rosemary. The maximum extract yields were found in July (15.57%) for sage and in June (30.48%) for rosemary. The sage oil was characterized by the presence of main components: camphore (20.73-26.07%), α-thujone (13.84-21.96), 1, 8-cineole (13.94-20.40%), ß-thujone (7.07-9.34%) and ß-caryophyllene (2.28-9.19%). Fourteen compounds of rosemary essential oil were identified and the main components were found as camphore (14.77-31.12%), 1, 8-cineole (7.70-26.18%), α-pinene (3.53-9.75%) and borneole (5.07-13.03%). Antiradical activities of sage and rosemary essential oils were found as IC 50=2492.84-6645.43 μg ml-1 and IC50=370.03- 2812.50 μg ml-1, respectively. Antioxidant capacities were also 25.20-43.46 mg AAE g-1 essential oil for sage and 18.53-37.95 mg AAE g-1 essential oil for rosemary. Sage and rosemary essential oils distilled from the early season (June) harvested leaves had the highest antioxidant activity, expressed as low concentration providing 50% inhibition of antiradical activity and high levels antioxidant capacity. Total phenolic content was between 85.33-110.52 mg GAE g-1 extract for sage and 94.29-104.44 mg GAE g-1 extract for rosemary. It was the lowest in June and the highest July in both extracts. Both antiradical activities and antioxidant capacities changed significantly depending on the phase in the growing season.
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Rosemary leaf extracts were obtained by supercritical fluid extraction (SFE) and Soxhlet extraction. Their chemical compositions were evaluated by GC-MS. The extracts were analyzed for compounds reported in the literature as showing antimicrobial and antioxidant activities. The rosemary extracts were tested with regard to antioxidant (DPPH radical scavenging and total phenolic content - Folin-Denis reagent), antibacterial (Gram-positive bacteria - Staphylococcus aureus ATCC 25923 and Bacillus cereus ATCC 11778 - and Gram-negative bacteria - Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) and antifungal (Candida albicans) activities. Antioxidant, antibacterial and antifungal activities of the SFE extracts were confirmed.
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The chapter summarises the evidence pertaining to the biobehavioural effects of selected herbal extracts, concentrating on evidence from well-controlled human trials. The focus is on cognition enhancement but will include some relevant material on modulation of mood. There is good evidence that certain extracts have cognition-enhancing properties. These include extracts of Ginkgo, Ginseng, Salvia, Guaraná, Lemon balm, Bacopa and others. In the domain of mood Lemon balm has consistently been shown to have a calming effect. Evidence for other herbals is less clear although cocoa polyphenols may have anti-fatigue effects. One constant challenge for the psychopharmacology of herbal extracts is the use of standardised extracts and the use of multiple extracts in some medicinal systems. New technologies used to meet these challenges will be discussed briefly.
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A gas chromatographic-mass spectrometric (GC-MS) method for the simultaneous identification and quantification of seven major phenolic and terpenic compounds in Rosmarinus officinalix L. was developed. The compounds were identified as trimethylsilyl (TMS) derivatives of phenolic acids (caffeic and rosmarinic acid), phenolic diterpene (carnosic acid), and pentacyclic triterpenes (ursolic, oleanolic, betulinic acid and betulin). These compounds have been identified by retention time and comparison of mass spectra. The procedure involves ultrasonic extraction using solvent mixture of tetrahydrofuran and ethanol. Extracts were fractionated by size exclusion chromatography (SEC) after purifying on graphitised carbon. The fraction with phenolic and terpenic compounds was derivatised prior to GC-MS analysis using N-methyl-N-trimethylsilyl trifluoroacetamide (MSTFA) as a derivatisation reagent. The derivatisation process was optimized regarding temperature and reaction time. The linearity of the method was tested in concentration range 4-25 mg L-1. The correlation coefficients (r2) were in the range of 0.997 to 0.999. The average recoveries for all compounds ranged from 80 to 82%. The GC-MS technique is specific and sensitive, and can be used for simultaneous identification and determination of a wide range of phenolic and terpenic compounds in different plants even at trace levels.
The phenolic diterpene carnosic acid appears to be the main substance for general oxidation leading to artifacts withγ-or δ-lactone structure in extracts ofRosmarinus officinalis andSalvia officinalis. Until now it was only possible to prepare carnosic acid by hydrogenolysis of carnosol. A semipreparative HPLC method has been developed isolating carnosic acid among other phenolic diterpenes. The separated substances were identified by13C-nuclear magnetic resonance (NMR),1H-NMR, mass and IR spetroscopy. Conversion of carnosic acid and carnosol to other phenolic diterpenes was investigated by HPLC.