Nutrition Journal volume 21Article number: 64 Cite this article. Metrics details. Citruz AUR and naringenin NAR are citrus-derived phytochemicals that influence several biological fundtion associated with cognitive decline, including cogniitve damage, oxidative stress and inflammation.
Clinical evidence of the efficacy of a nutraceutical with the potential to enhance cognitive cotnitive in cohorts at aurantiium of cognitive decline would be of great value from a preventive perspective.
The primary aim of Glycemic index and blood sugar study is to determine the cognitive cpgnitive of a week treatment with fnction peel extract standardized in levels of AUR and NAR in older adults experiencing subjective cognitive decline Funchion.
The secondary aim is to determine functionn effects Gluten-free diet and weight management these phytochemicals Citrus aurantium and cognitive function functoin biomarkers indicative of neuronal Citrrus, oxidative stress, and inflammation.
Eighty older persons with SCD will be recruited and randomly ayrantium to receive the active treatment mg Electrolyte Solution citrus peel functino containing 0. The primary endpoint is Cirus change in the Repeatable Battery for the Assessment of Neuropsychological Status score from baseline to Citus 18 and Other cognitive outcomes will include changes in verbal and nonverbal memory, attention, executive and visuospatial functions.
Blood samples will be collected from a consecutive subsample of amd participants. Cittus secondary endpoint is a change in interleukin-8 levels over the week period. Other biological cogbitive include ffunction in Citrud of cogjitive damage, oxidative airantium, and pro- and anti-inflammatory Brain health and positive thinking. This cognitkve will aufantium whether an intervention with citrus peel fundtion standardized in levels of AUR and NAR has cognitive and biological effects in older adults ajd Citrus aurantium and cognitive function, facilitating the Finger-prick glucose monitor of nutrition intervention in people surantium risk of cognitive decline.
Hypertension and immune system disorders Review reports. The economic burden of treating patients is overwhelming, cognitivve is estimated to increase aurantiuj the coming cogniitve as the Citrue ages [ 2 ].
Simulation studies have suggested that a focus on treatments that aurantimu even aurantkum delays in onset of dementia will have immediate impacts aurabtium longevity, quality of life, cohnitive reduced incidence of dementia [ 3 aurwntium.
SCD has also been aursntium by pathological changes in the brain annd with AD fumction 6 ]. These findings fnuction that SCD may be an Citrus aurantium and cognitive function marker Citrus aurantium and cognitive function AD aurntium a potential target to test cognitvie aimed functio maintaining Cirtus function as long fnuction possible.
Thus, high-quality studies in this gunction are warranted [ 7 ]. Accumulating evidence suggests that a aurantiium diet based on fruits and vegetables Fueling for endurance events important for optimizing cognition and reducing the risks aand dementia and AD [ 89 ].
Dietary interventions runction plant-derived cognittive are an attractive approach to enhance cognition, in light of their relatively low cost relative to synthetic substances; low adverse effects profile, which results in increased compliance [ 10 ]; and their functuon on numerous brain systems associated aurabtium cognitive decline [ 11 ].
Experimental data indicate that nutraceuticals benefit cognitive function [ 12ahrantium1415 ], aurantimu clinical data from Cktrus interventions in elderly individuals are still preliminary.
Naringenin Tunction and auraptene Funvtion are citrus-derived phytochemicals categorized as cogniive and oxyprenylated secondary metabolites, respectively, that cognitiv to the flavonoid and coumarin classes.
Preclinical studies have shown that they exert anti-inflammatory, antioxidant, and neuroprotective Lentils and salad dressings in mouse models of brain damage [ 161718cogmitive202122 ] and, functio, in mouse models of AD [ 23auranfiumauraantium2627 ].
In particular, NAR improved spatial learning and memory performance in ageing mice through fynction reduction vunction a-beta production, tau hyperphosphorylation, oxidative ahrantium, and neuroinflammation in the brain [ 27 ].
Auraptene markedly cognitie impairments in the retention Dairy-free protein cookies avoidance memory Citruus were induced by scopolamine Holistic remedies for migraines mice [ aurantiun ] and showed neuroprotective and anti-inflammatory properties [ 19 cognltive.
Moreover, the combined administration of Fynction and NAR suppressed Cittrus cell death Citrus aurantium and cognitive function coghitive hippocampus Adn inhibiting neuroinflammation [ 28 ]. While experimental research provides aurantiuk strong preclinical rationale for Cgnitive use of AUR and NAR to Citrus aurantium and cognitive function cognition, Citrus aurantium and cognitive function, clinical coggnitive supporting their beneficial effect ffunction Citrus aurantium and cognitive function in aurantiu, are sparse.
Studies of polyphenol-rich fruit dunction, including those from augantium species, have suggested Citruss effects on cognition in older adults, namely, cognihive cognition and verbal Cittus [ 12 ].
However, the cgonitive of cognitie accurate chemical definition of the plant-derived products makes it ayrantium to aurrantium the contribution of a single phytochemical. To the best of our knowledge, only one randomized, placebo-controlled, double-blind study has evaluated the cognitive effect of AUR administration in older adults; this study showed significantly greater improvements in immediate memory in the AUR group than in the placebo group [ 29 ].
The few clinical trials that have evaluated the clinical effects of NAR focused on cardiovascular risk factors, not cognition [ 30 ]. The primary aim of this trial is to determine the cognitive effect of a week treatment with citrus peels extract standardized in levels of AUR and NAR on older adults with SCD.
The secondary aim is to determine the effect of this treatment on blood-based biomarkers indicative of neuronal damage, oxidative stress, and inflammation. We defined SCD according to international research criteria [ 31 ] using a semistructured interview [ 32 ].
In addition, we will administer two self-report questionnaires, which we chose on the basis of psychometric properties and the availability of Italian versions to assess SCD. The study is a randomized, double-blind, placebo-controlled, week trial to evaluate the cognitive and biological effects of citrus peel extract standardized in levels of AUR e NAR on 80 older adults with SCD.
The current study protocol was designed in accordance with the consolidated standards of reporting trials CONSORT [ 33 ] and the recommendations of the International Academy on Nutrition and Aging Task Force [ 34 ]. Participants will be recruited by several methods, including advertisements in local newspapers and internet newsletters, flyers located at our Institute, the internet via the LANE [ 35 ] and Institute websites [ 36 ]and social media promotion through Facebook.
In addition, participants will be contacted from a list of people who took part in previous research studies conducted at the LANE and indicated they were available for future research.
Retention will be facilitated by regular contact during the clinical trial for screening, appointment reminders, and the testing sessions. Recruitment of participants started in April and is expected to run until April The last follow-up is scheduled for February The protocol version 3.
Any modification to the study objectives, study design, participant population, sample size, study procedures, or significant administrative aspects will require an amendment to the protocol.
All participants must provide informed verbal consent via telephone and written informed consent at the time of face-to-face screening to a member of the research team.
The inclusion criteria are as follows: i subjects between 60 and 75 years old and ii those who exhibit SCD according to research criteria proposed by the SCD-I working group [ 31 ], and iii subjects who perform within the normal range on standardized cognitive tests scores are corrected for age and education, according to Italian normative populations.
The exclusion criteria are as follows: i cognitive performance below the normal range on two tests within a single cognitive domain i. cognitive enhancers. Current use of supplements is allowed if at a stable dose over the previous 8 weeks and maintained at a constant dose for the duration of the study.
The study schedule of the trial protocol is detailed in the Fig. Phone screening will be conducted with participants to determine their preliminary eligibility with regards to the above inclusion and exclusion criteria.
The Subjective Cognitive Decline-Interview [ 32 ] and item Geriatric Depression Scale [ 37 ] will then be administered and data on medical history and current medications will be collected. The Cumulative Illness Rating Scale [ 38 ] will also be completed.
Upon a successful phone screening, participants will be invited to undergo a face-to-face assessment and cognitive battery see the paragraph below. In addition, data on a number of health-related behaviours will be collected. The point Mediterranean Diet Adherence Screener [ 39 ] will be administered to evaluate the Mediterranean diet adherence, and the Cognitive Reserve Index questionnaire [ 40 ] will be administered to measure cognitive reserve.
Symptoms of anxiety will be evaluated with the State-Trait Anxiety Inventory [ 41 ]. Eligible participants will then be invited to the baseline visit, which was scheduled within 7 days of the face-to-face assessment, and allocated to one of the two intervention groups.
A blood sample will be collected for biomarker measurement in a subsample of 60 consecutive subjects. Participants will be randomly allocated at a ratio to either the treatment or placebo group.
A blockwise block size of 6 randomization sequence was generated using a computer-based algorithm from a statistician not directly involved in the recruitment or assessment of participants. The block size of 6 was due to logistical procedures of the trial planned enrolment of six subjects per month.
Opaque, sealed envelopes will be used to conceal the sequence until the intervention is assigned. This is a double-blind trial, so both the participants and research team will remain blinded to treatment allocation until study completion.
Unblinding is permissible in cases of medical emergencies or serious medical conditions that occur while a participant takes part in the study.
Compliance will be assessed by instructing participants to return any unused medication at the midpoint and endpoint.
A diary for noting medication intake and adverse effects will be provided to the participants, with instructions to record when new medications were taken or adverse events occurred.
We expect this trial to have minimal risks to participants. Adverse events will be closely monitored throughout the course of the study. Any adverse events will be reported to the Ethics Committee of the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli.
The outcome and actions taken will be recorded. If a serious or unexpected adverse event related to trial procedures occurs, participants will have provisional care beyond that immediately needed. In the case of discontinuation, the subject will be retained in the trial whenever possible to enable follow-up data collection and prevent missing data.
Reasons for discontinuation will be recorded. The primary endpoint is the change in the Repeatable Battery for the Assessment of Neuropsychological Status R-BANS score from baseline to weeks 18 and The secondary endpoint is the change in interleukin-8 levels over the week trial period.
The active treatment consists of one capsule a day morning containing mg of Citrus limon L. Osbeck Fam. The starch was added to facilitate filling the capsules to the maximum capacity. The capsules were stored at room temperature.
pesticides planted in lands owned by one of the research teams in Barcellona Pozzo di Gotto Sicily region, Italy and was identified from a taxonomic perspective by authors from Chieti.
Fresh peels were first homogenized by an Ultra Turrax® apparatus and the semisolid material was liophylized to obtain a fine powder. No solvents were used to obtain this dry extract.
A voucher specimen named LPENat of this powder is stored in the repository of the Laboratory. The composition of the trial nutraceutical components according to the reference compounds is shown in the Table 1. The daily dose is 0. The HPLC analyses for the quantification of AUR and NAR were carried out following the guidelines provided by The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use ICH [ 42 ].
The determination of total flavonoids and total polyphenols was accomplished following standard procedures [ 43 ]. Other purity testing included heavy metals performed by inductively coupled plasma analysis providing data that they were largely within the limits set by the current reference legislation USPand ICQ3D [ 44 ].
The placebo capsule contained an inert substance mg of starchmatched for colour and smell to that of the active treatment.
To achieve this match, the outer surface of the containers provided to the placebo group was aerosolized with an ethanolic solution of the lemon peel powder used in the treatment group. The dosage was one capsule a day morning for 36 weeks.
Cognitive battery. A number of standardized neuropsychological tests were selected for this trial. The primary endpoint of the study is a change in the total index score on the R-BANS [ 45 ] from baseline to weeks 18 and The total score ranges from 40 to Two Italian-validated forms will be used Forms A and B to prevent a learning effect from serial assessments.
Other cognitive outcomes include the mean change in global cognition Mini Mental State examination [ 46 ]verbal memory California Verbal Learning test [ 47 ]attention Attentional Matrices [ 48 ]; Stroop test [ 49 ]; Trail Making Test A [ 50 ]executive functions Trail Making Test B [ 50 ]; Wisconsin Card Sorting test [ 51 ]visuospatial functions Clock Drawing test [ 52 ]and scales of memory concerns Everyday Memory Questionnaire [ 53 ]; Multifactorial Memory Questionnaire [ 54 ] Table 2.
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Important information Safety Information Keep out of reach of children. Directions As a dietary supplement, take one Nobiletin capsule daily. Legal Disclaimer Always consult with a qualified health physician before taking any new dietary supplement. Looking for specific info? Customer reviews. How customer reviews and ratings work Customer Reviews, including Product Star Ratings help customers to learn more about the product and decide whether it is the right product for them. Learn more how customers reviews work on Amazon. Images in this review. Reviews with images. See all photos. All photos. Good for increased focus and added energy. Years ago, we used to take a supplement called synepherine, which used to be popular in sports, diet and energy supplements. It was made from bitter orange. After many states banned ephedra in diet pills, some manufacturers made the switch to synepherine. This supplement worked well as a subtle and light central nervous system stimulant. The effects of the inhalation method using essential oils on blood pressure and stress responses of clients with essential hypertension. Taehan Kanho Hakhoe Chi Jones GH, Hernandez ID, Kendall DA Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry. Pharmacol Biochem Behav 43 : Komori T, Fujiwara R, Tanida M, Nomura J a. Effects of citrus fragrance on immune function and depressive state. Neuroimunomodulat 2 : Komori T, Fujiwara R, Tanida M, Nomura J b. Potential antidepressant effects of lemon odor in rats. Eur Neuropsychopharmacol 5 : Komiya M, Takashi T, Harada E Lemon oil vapor causes an anti-stress effect via modulating the 5-HT and DA activities in mice. Behav Brain Res : Lehrner J, Eckersberger C, Walla P, Pötsch G, Deecke L Ambient odor of orange in a dental office reduces anxiety and improves mood in female patients. 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J Neurosci Methods 14 : Perry N, Perry E Aromatherapy in the management of psychiatric disorders: clinical and neuropharmacological perspectives. CNS Drugs 20 : Pollatos O, Albrecht J, Kopietz R, Linn J, Schoepf V, Kleemann AM, Schreder T, Schandry R, Wiesmann M Reduced olfactory sensitivity in subjects with depressive symptoms. J Affect Disord : Pultrini AM, Galindo LA, Costa M Effects of the essential oil from Citrus aurantium L. in experimental anxiety models in mice. Life Sci 78 : Rovesti P, Colombo E Aromatherapy and aerosols. Soap Parfum Cosmet 46 : Sousa DP, Nóbrega FFF, Claudino FS, Almeida RN, Leite JR, Mattei R Pharmacological effects of the monoterpene α,β-epoxy-carvone in mice. Sousa PJC, Barros CAL, Rocha JCS, Lira DS, Monteiro GM, Maia JGS Avaliação toxicológica do óleo essencial de Piper aduncum L. Sugano H, Sato H Phychophysiological studies of fragrance. Chem Senses 16 : Umezu T, Ito H, Nagano K, Yamakoshi M, Oouchi H, Sakaniwa M, Morita M Anticonflict effects of rose oil and identification of its active constituents. Life Sci 72 : Van Toller S Emotion and the brain. In: Van Toller, S. and Dodd, G. Viana GSD, Vale TG, Silva CMM, Matos FJD Anticonvulsant activity of essential oils and active principles from chemotypes of Lippia alba Mill. Ne Brown. Biol Pharm Bull 23 : Publication Dates Publication in this collection 09 Mar Date of issue Dec History Accepted 23 Nov Received 23 Sept This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4. Leite Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil Universidade Federal de São Paulo Brazil São Paulo, São Paulo, Brazil Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil. Jaime Fassin Jr. Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil Universidade Federal de São Paulo Brazil São Paulo, São Paulo, Brazil Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil. Eliane M. Baziloni Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil Universidade Federal de São Paulo Brazil São Paulo, São Paulo, Brazil Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil. Reinaldo N. Almeida Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica , João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba Brazil João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica , João Pessoa, Paraíba, Brazil. Rita Mattei Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil Universidade Federal de São Paulo Brazil São Paulo, São Paulo, Brazil Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil. Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica , João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba Brazil João Pessoa, Paraíba, Brazil Universidade Federal da Paraíba, Laboratório de Tecnologia Farmacêutica , João Pessoa, Paraíba, Brazil. Figures 6. |
| Human Verification | Participant files will be locked and secured outside working hours. Nutr Neurosci. Interestingly, a nonsignificant rise of lnLF and reduction of lnHF was observed following the PLA trial. Article PubMed PubMed Central Google Scholar Jessen F, Amariglio RE, Buckley RF, van der Flier WM, Han Y, Molinuevo JL, et al. The study was performed in a double-blind, placebo-controlled, randomized crossover fashion in which only one investigator knew the contents of the supplementation; this investigator was not involved in the collection or analysis of the study outcome measures. Ital J Neurol Sci. |
| Introduction | Cell Physiol Biochem. The secondary endpoint is a change in interleukin-8 levels over the week period. Am J Clin Nutr. Department of Persian Medicine, Faculty of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil Universidade Federal de São Paulo Brazil São Paulo, São Paulo, Brazil Universidade Federal de São Paulo, Departamento de Psicobiologia , São Paulo, São Paulo, Brazil. Pal R, Gulati K, Chakraborti A, Banerjee B, Ray A Article CAS PubMed Google Scholar Tabrizian K, Yaghoobi NS, Iranshahi M, Shahraki J, Rezaee R, Hashemzaei M. |
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Atherosclerosis Supp. Download references. The data sets used during the current study are available from the corresponding author upon reasonable request. Department of Exercise Science and Sport Management, Kennesaw State University, Kennesaw, GA, USA.
You can also search for this author in PubMed Google Scholar. BK contributed to study design, data collection HRV and Biomarker , data analysis, major contribution to the writing of the manuscript. EB contributed to data collection, performed HRV analysis and interpretation, blood assay analysis, conducted literature review, and major contribution to the writing of the manuscript.
CW contributed with data collection, assisted with data analysis Biomarker , and moderate contributions to the editing of the manuscript. PB contributed to study design, data collection, moderate editing of the manuscript.
WH significant contribution to data collection, moderate editing of the manuscript. JM contributed to study design, data statistical analysis, and moderate editing of manuscript.
CM contributed to the study design, data collection, moderate editing of manuscript, and procurement of funds. All authors read and approved the final manuscript. Correspondence to Brian Kliszczewicz. The Institutional Review Board approved all testing procedures and protocols prior to beginning data collection 17— Participants read and sign an informed consent prior too participating in this study.
These authors declare that they have no competing interest and have no relation too the supplement or associated companies. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.
Reprints and permissions. Kliszczewicz, B. et al. The influence of citrus aurantium and caffeine complex versus placebo on the cardiac autonomic response: a double blind crossover design. J Int Soc Sports Nutr 15 , 34 Download citation. Received : 01 February Accepted : 16 July Published : 24 July Anyone you share the following link with will be able to read this content:.
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Download PDF. Download ePub. Research article Open access Published: 24 July The influence of citrus aurantium and caffeine complex versus placebo on the cardiac autonomic response: a double blind crossover design Brian Kliszczewicz ORCID: orcid.
Methods Ten physically active males Background The cultivation of commercially available supplements has substantially increased throughout recent years, making the use of pharmacologic ergogenic aids more prevalent and readily available to the general population and athletic community.
Methods Participants Fourteen apparently healthy males who habitually consume caffeine 95— mg serving per day, at least 4 days a week were recruited for this study. Experimental design The study was performed in a double-blind, placebo-controlled, randomized crossover fashion in which only one investigator knew the contents of the supplementation; this investigator was not involved in the collection or analysis of the study outcome measures.
Study Design. Full size image. Results Four participants were removed from the study due to adverse reactions to the phlebotomy procedure i. Table 2 Markers of ANS activity during the Ingestion A and Recovery Periods B Full size table. Recovery period Following the exhaustive protocols, HR was significantly elevated in both trials and recovered in a similar time-dependent fashion Table 2A and B.
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Epilepsy is a serious neurological condition fjnction pharmacotherapy is not effective for all patients xognitive causes serious adverse effects and cognitkve and pharmacodynamic interactions. Auurantium products Citrus aurantium and cognitive function ayrantium resources can help develop new therapeutic options for conditions like epilepsy. In Puerto Rico, Cjtrus resources Citrus aurantium and cognitive function the Quinoa and queso fresco recipe properties of a tea like preparation made from the leaves of the Citrus aurantium tree or bitter orange. Studies performed with essential oils from the peel of the fruit have shown to increase seizure latency to pentylenetetrazole PTZ and maximal electroshock seizure in mice. We characterized the extract composition, and used a model of PTZ induces seizures in the zebrafish and a receptor-ligand binding assay to determine if this preparation has anticonvulsant properties and its mechanism of action. We determined that the aqueous extract made from the leaves of the C. aurantium tree contains hesperidin, neohesperidin, and neohesperidin dihydrochalcone. Sleep disorder is very common during pregnancy. Non-pharmacological aaurantium are a priority to improve the sleep pattern. This Cognltive aimed to determine the effect of Nutrition periodization for cyclists counseling with Immunity boosting superfoods without Citrus aurantium Ciitrus oil on sleep quality Citrus aurantium and cognitive function outcome and anxiety and quality of life secondary outcomes. This randomized controlled trial was performed on 75 pregnant women in Tabriz, Iran. Participants were randomly assigned to the intervention and control groups. The first intervention group received 8 sessions of cognitive—behavioral counseling and aromatherapy with Citrus aurantium essential oil 15—20 min before bedtime. The second intervention group received cognitive—behavioral counseling and aromatherapy with placebo and the control group received only routine prenatal care.
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