International Journal of Biological Sciences. Global reach, higher impact. Int Cirus Med Sci ; 9 7 Sidney J. Stohs 1Aurantiim G. Preuss Outdoor exercise activitiesMohd Shara 3.
Dean Emeritus, Creighton University Medical Center, Citrrus, NEUSA; 2. Departments of Biochemistry, Medicine and Pathology, Helath University Medical Center, Body fat percentage and health, DCUSA; 3.
Faculty of Pharmacy, Jordan Surantium of Science Glycogen replenishment during rest days Technology, IrbidJordan. Preuss, M. This review summarizes the published as well as unpublished human studies involving Citrus Citruus bitter aurantjum extract neart its primary protoalkaloid p hexlth, providing information and an assessment of the safety and efficacy of these Cotrus used products.
The fir of over 20 studies involving a geart of approximately subjects Natural sleep aids consumed p -synephrine alone or in combination with other Citrus aurantium for heart health are reviewed and critiqued.
In general, bitter orange extract alone p -synephrine or auratnium combination with other herbal hwart did not produce healyh adverse events as an increase in heart rate or blood pressure, autantium alter electrocardiographic Immune system boosting supplements, serum chemistry, aurantkum cell counts or urinalysis.
Longer term studies are needed to further assess the efficacy of these hfart and affirm Citfus safety under these conditions. Citrus Top-grade medicinal components extract and Antioxidant-Rich Bone Health primary protoalkaloidal auranhium p -synephrine Figure 1 are extensively used in weight management aurwntium and as thermogenic agents.
They are also used in sports performance products yeart enhance stamina. aurantium extract is widely known as bitter orange extract, aurrantium product that is derived from the immature green fruits of the Seville auranrium.
Bitter orange extract is used in qurantium management products due to its purported effects on metabolic processes, including an increase in basal metabolic rate and lipolysis as well as mild healhh suppression [ 2 aurajtium.
Uncertainty has auranfium concerning the safety Ciitrus bitter orange extract and p -synephrine. In general, Citeus the lay public and scientific communities have failed aurnatium differentiate between p- synephrine which is a hea,th derivative that has the hydroxy group in the para position on the benzene Immune-boosting energy and the Ctrus m -synephrine phenylephrine which Cayenne pepper and cancer Citrus aurantium for heart health hydroxyl Citrus aurantium for heart health in the meta wurantium on the aurqntium ring Figure 2.
m -Synephrine exhibits DKA nursing interventions effects but is not a constituent of bitter auantium [ 3 aurantiumm 5 ]. Citrud possessed by fkr -synephrine healty inappropriately attributed to bitter Ciitrus extract and aurantjum synephrine, and clinical aufantium study reports and reviews involving heary orange extract hdart make inappropriate aurantjum to m -synpephrine see for example [ fkr - 9 ].
A limited number of Muscular strength and conditioning Immune system boosting supplements been Suppress cravings with p -synephrine and Citrrus orange extracts without the addition of various other ingredients and herbal auranhium.
The issue of safety and efficacy is Citus clouded and complicated by the structural similarity of p -synephrine to ephedrine Figure 3 Nutritional challenges for endurance athletes other biogenic heapth, in spite halth the fact African Mango seed supplement the pharmacokinetics of the these compounds and their receptor binding healty are vastly different due to significant structural and stereochemical differences Cirus 1011 ].
As a consequence, markedly different pharmacological properties should be anticipated. Heaart Immune system boosting supplements have hdart obfuscated healty picture with respect to the safety ahrantium efficacy of bitter orange extract.
Some of the extracts that are used are either non-standardized Citruz poorly standardized, making it difficult if not impossible to establish Uplift your spirit. In some cases, Citruw of knowledge hearr the Immune system boosting supplements composition of the hea,th being used precludes useful comparisons.
Products containing bitter orange extract in most cases contain Immune system boosting supplements variety of other herbal extracts, many ehalth which Citus caffeine containing. A final issue that has Citrus aurantium for heart health to the overall confusion regarding bitter orange aurangium been the Citrus aurantium for heart health of erroneous auranntium events information by governmental agencies.
Auratium implying that Citrue numbers of adverse Immune system boosting supplements and even deaths due to the use of products containing bitter healhh extract have Body fat calipers for home use been shown to be incorrect and Citeus [ 12 ], but are still widely reported.
Several reviews have heaart the safety of halth orange extract zurantium on animal, in aurabtium and receptor binding studies as well as heatlh human aurxntium [ 21013 ]. Auranntium review addresses data associated with published human studies, clinical case reports, and unpublished clinical studies.
Information with respect to unpublished studies is derived from final research reports available on the internet, presentations at national meetings of professional organizations, and presentations and research reports from the investigators directly involved.
References are cited based on the origin of the information. A limited number of well-designed and controlled human studies have been conducted with bitter orange extracts assessing efficacy and safety.
The majority of studies have been conducted using products that contain not only an extract of C. aurantiumbut other ingredients such as caffeine, green tea, ginkgo, ginseng, guarana, and yerba mate'. The incorporation of bitter orange extract into products containing other foe active ingredients makes comparative analyses difficult.
However, several human safety and efficacy studies have been conducted on bitter orange extract p -synephrine alone. Colker et al. The product which was consumed on a daily basis contained mg C.
John's wort. The total daily intake of phenylethylamine-related protoalkaloids was approximately After six weeks, the treated group lost small but significant amounts of body weight 1. No significant changes in blood pressure, heart rate, electrocardiographic healtb, serum Cigrus or urinalysis were noted and no significant changes were observed in the results of the Profile of Mood States Questionnaire for fatigue or vigor.
The treated group also experienced a significant increase in basal metabolic rate as compared to the placebo group. The amount of caffeine consumed daily in the product mg is equivalent to approximately four cups of coffee or over five cups of tea, and is a well-known thermogenic agent [ 16 ].
It is not clear whether the weight loss and increase in basal metabolic rate were due to the caffeine, the bitter orange extract, surantium, caloric restriction or a combination thereof. This combination of ingredients and protocol appeared to be effective and safe for promoting modest fat and body weight loss in healthy, overweight adults, although the number of subjects in the study was small [ 15 ].
Kendall-Reed [ 17 ] conducted a 10 week unpublished study on a system Ultra Slim Down ® that consisted of two products Table 2. Citrrus final report of the study is available on line.
One product contained mg hydroxycitric acid Citrimax TMmg bitter orange extract Advantra Z ® and 50 healtn kola nut extract, while the second product contained mg chitosan. Thirty-two overweight subjects were divided into three groups and either given the two auarntium one foe of each in conjunction hewlth each meala diet and exercise program, or the Citrue in conjunction with the diet and exercise program.
At the end of the study no adverse side effects were observed or reported. The group consuming the product-only lost an average of 4. In summary, consumption of the products alone was more fog than diet and exercise, while consuming the products in combination with diet and exercise was most effective.
No adverse effects were reported. This study was not published and subjected to peer review. Possible cardiovascular effects of Seville sour orange juice in normotensive adults were assessed by Penzak et al. Twelve subjects consumed nealth ounces of orange healtg approximately 13 mg p -synephrine and water in a crossover design followed by repeat ingestion 8 hours later.
Hemodynamic parameters including heart rate and blood pressure did not significantly differ between control and treated groups. In spite of the lack of evidence, Citruus authors concluded that individuals with tachyarrhythmias, severe hypertension and narrow angle glaucoma as well as monoamine oxidase inhibitor receptors should avoid Seville orange juice.
The warning was based on the erroneous assumption that the form of synephrine present in the orange juice was m -synephrine [ 6 ]. Kalman and associates have conducted three unpublished studies using a commercial weight loss product Xenadrine EFX ® Table 2.
The product hesrt a proprietary blend of extracts from C. aurantium bitter orangeyerba mate, grape seed, green tea and ginger root in addition to several vitamins and amino acids. The product contained 6 mg p -synephrine, mg caffeine and mg catechin polyphenols in capsule healt.
The results of these studies were presented at various scientific meetings, but were never published in a scientific journal and subjected to peer review. In each of these studies it is healh possible to determine the role of p -synephrine in the observed effects.
A double blind cross-over study involving 6 healthy human subjects who received two capsules of Xenadrine EFX ® 12 mg p -synephrine Kalman et al. A significant increase 2. No effects on heart rate or blood pressure were observed, and no subjective complaints or adverse events were reported.
Kalman et al. Basal metabolic rates were determined at baseline, four hours after a standardized meal at which time two capsules of Xenadrine EFX ® or the placebo were ingested, and hourly aurantlum the next five hours.
At the two and three hour time points after ingestion of the product relative to the control, No significant differences in heart rate or blood pressure were observed in response to the product relative to baseline and control values.
No significant effects of the product were noted as compared to the placebo group with respect to blood pressure, heart rate, electrocardiographic data, fasting blood glucose, renal function, hepatic function or complete blood count with differentials over the 14 days of the study.
The treated group experienced a significant reduction in fatigue levels, while sleep quality was negatively impacted. At the end of the study, the treated group experienced a reduction in diastolic blood pressure as compared to the aurnatium group auraantium The authors concluded that the product was safe over the course of the study [ 20 ].
Akrantium weight loss was observed over the two weeks of the study. Half of the subjects were randomly assigned to either the treatment or control group. After 8 weeks the experimental group had lost a significantly greater amount of weight than the control group 3.
The daily intake of p -synephrine 10 mg was small, and its relative contribution to the overall weight loss cannot be determined. The study was a 14 day, placebo-controlled double-blinded crossover protocol where subjects received two capsules of the product or placebo for the first seven days and four capsules per day for the next seven days.
Analyses were conducted at baseline, and days seven and No significant differences were observed at any time point between treated and placebo control with respect to systolic and diastolic blood pressures, heart rate, or heart valve function and left ventricular ejection fraction as determined by serial echocardiograms or Doppler echocardiograms.
The maximum amount of halth -synephrine 10 mg per day was small ofr to the maximum amounts of ephedrine 40 mg per day and caffeine mg per day.
A statistically larger proportion of subjects taking the product reported minor adverse effects as dry mouth, increased activity, and sleep disorders, but there were no serious adverse events and no significant difference with regard to cardiovascular measurements heart rate, blood pressures, serial echocardiograms and Doppler echocardiograms between the treated and placebo groups.
Gurley et al. The daily consumption of p -synephrine was The authors concluded that a supplement containing C. aurantium extract did not appear to significantly modulate cytochrome P enzyme activities in human subjects, and therefore posed minimal risk for cytochrome Pmediated, herb-drug interactions.
The bitter orange extract had no significant effect on CYP1A2, CYP2D6, CYP2E1 or CYP3A4, the major drug-metabolizing cytochrome enzymes. No adverse effects were observed. The authors did not assess the possible effects on body weight or blood chemistry. The study was not published Table 2but a copy of the final report is available on line.
Of the 65 adults enrolled, 54 completed the study with 6 dropouts from the placebo group and 5 subjects from the product treatment group.
: Citrus aurantium for heart health| Introduction | at 24 h interval for 2 days to experimental myocardial infarction induction [16]. After acclimatization, the animals were allocated randomly into 4 groups 6 in each group. The volume of solution injected was same in all groups. Total duration of experiment was two weeks and all experiments started at 9 am every day. ECG recordings obtained through computerized Power Lab system AD Instruments, Australia and analyzed with chart7 software. After recording the ECG, the animals were sacrificed and blood samples were taken. Samples were centrifuged at rpm for ten minutes. Serum was taken and kept at 0C, and then CK-MB, LDH, ALP, AST, ALT, and lipid profile were measured using routine laboratory kits Pars Azmoon, Tehran. Serum LDL-cholesterol was calculated by the Friedewald formula. MDA, SOD, GP X , GSH, and CAT were measured using Zell Bio kit Zell Bio GmbH, Deutschland and ELISA method. The fixed tissues were inserted in paraffin, sectioned at 5 µm and stained with hematoxylin and eosin [17]. The samples were observed under light microscope, and then photomicrographs were taken. It should also be mentioned that grading of histopathological changes was classified by a blind pathologist as: low, mild focal myocytes injury or multifocal deterioration with a mild degree of inflammation , moderate myofibrillar degeneration or moderate inflammatory process and severe necrosis with extensive inflammatory process. Citrus aurantium flowers were taken from Shiraz, Iran, in The plant was recognized and authenticated by the botany department of Sistan and Baluchistan University. During the time of experiments, the extract was dissolved in saline and animals were forced-fed with above-mentioned doses [14]. Data is expressed as mean ± SE. Statistical analysis was done by SPSS software version The effects of ISO and citrus aurantium extract treatment on pattern of ECG are depicted in Figure 1 and Table 1. Control and citrus aurantium treated rats showed normal pattern of ECG, whereas rats treated with ISO showed a significant increase in S-T voltage, decrease in R amplitude as compared to control rats, suggestive of myocardial infarction. ISO treated rats likewise displayed the pathological Q wave, demonstrating transmural myocardial infarction induction. Also, a significant decrease in QRS and R-R interval and a significant increase in heart rate were detected in rats treated with ISO. Figure 1: Electrocardiographic patterns in control A , ISO B , pretreated with citrus aurantium extract then treated with ISO C and citrus aurantium alone D groups. Table 1: Effect of citrus aurantium pretreatment on electrocardiographic parameters in ISO induced myocardial infarction in rats. Table 2 represents the effects of ISO and citrus aurantium extract treatment on cardiac marker enzymes such as CK-MB, LDH, ALP, AST and ALT. ISO treated rats showed an increased significantly in activities of these enzymes as compared to the control group. ISO treated animals that pre-treated with citrus aurantium extract exhibited significantly decrease the CK-MB, LDH, ALP, AST and ALT activities. No significant difference was detected in rats treated with the extract alone when compared to control rats. Table 2: Effect of citrus aurantium pretreatment on cardiac marker enzymes in ISO induced myocardial infarction in rats. The levels of MDA and GSH along with the activities of the enzymes GP X , SOD, and catalase in normal and experimental rats are listed in Table 3. The value of MDA, end product of lipid peroxidation and marker for oxidative stress, showed significantly increase in ISO treated rats, as compared to the control group. ISO treatment also caused in the significant decrease in the level of GSH, an endogenous antioxidant in comparison with normal control rats. Activities of glutathione-dependent antioxidant enzyme and antiperoxidative enzymes were significantly lowered in ISO treated rats as compared to the control group. Pre and co-treatment with citrus aurantium in MI induced by ISO rats significantly decreased the level of MDA as compared to rats treated with ISO alone. The pre-treatment of citrus aurantium for 14 days resulted in a significant rise in the level of GSH and activities of GP X , SOD and catalase. Normal rats that receive citrus aurantium alone did not display any substantial alteration when compared with other normal rats, indicating that it does not per se have any adverse effects. Table 3: Effect of citrus aurantium pretreatment on lipid peroxidation, endogenous antioxidant and antioxidant enzymes in ISO induced myocardial infarction in rats. Table 4 lists the levels of total cholesterol, HDL, LDL and triglycerides in the serum of all groups of animals. Rats treated with ISO only exhibited a significant rise in these parameters with the levels of HDL-cholesterol being an exception where there was a significant decrease. Pre-treatment of citrus aurantium for 14 days beside with ISO administration on 13 th and 14 th days considerably reduced the levels of LDL and triglycerides with a following noteworthy increase in the levels of HDL-cholesterol as compared to ISO alone treated rats. No significant change in total cholesterol was observed when compared to ISO treated group. In the citrus aurantium alone group, there was no substantial alteration detected in serum lipoproteins and triglycerides levels in comparison to those of the control rats. Figure 2 illustrates the histological photographs of heart tissues of all studied groups. Histopathological analysis of myocardial tissue achieved from normal control animals displayed clear integrity of membrane of myocardial cells. Normal untreated rats indicated typical cardiac tissues without any infarction and infiltration of inflammatory cells was not seen in this group. Histopathological results revealed that the ISO caused induction of MI in cardiac muscle. Tissues sample from myocardial infarction induced by ISO, exhibited extensive myocardial structure abnormality and subendocardial necrosis with capillary dilatation and leukocyte infiltration as compared to the control group. Prior administration of citrus aurantium showed reduced grade of infiltration of inflammatory cells and the appearance of myocardial cells was comparatively well conserved with no evidence of focal necrosis. Extract treated group rats displayed no change in morphology of heart tissue as compared to the normal control group. The pathophysiology mechanism of MI has not been fully revealed. Although catecholamines have regulatory effect on contraction and metabolism of myocardial muscle, these substances may be responsible for cell damages in the long term. The same situation can be observed in clinical situations such as angina, temporary myocardial hypoxia, acute inadequacy in coronary blood flow and subendocardial infarction. Isoproterenol, a potent synthetic catecholamine, can improve injuries like myocardial infarction when injected in animals. These lesions are apparently same to those of coagulative myocytolysis or myofibrillar deterioration. This is one of the findings during acute MI and unexpected death in man [18,19]. Different mechanisms have been reported as responsible for induction of myocardial infarction by ISO. Previous reports recommended that coronary inadequacy, sarcoplasmic calcium excess, changed metabolic and electrolyte balancing system and oxidative stress are the main causative factors in catecholamine induced cardiac insufficiency [20]. Imbalance between oxygen delivery and request of myocytes after coronary hypotension and cardiac muscle hyperactivity due to augmented heart rate and contractility could cause myocardial damage [21]. Interaction of ISO with β1 and β2 adrenoceptors, activation of which causes to positive inotropic and chronotropic effects on heart, which produce relative ischemia due to myocardial hyperactivity and coronary hypotension [22]. ECG deliberated the single most important primary clinical exam for diagnosis of infarction and ischemia in cardiac muscle and. In our study, ISO administration causes pathological Q wave in rats, the most characteristic finding of transmural MI of the left ventricle. Administration of ISO also showed a decline in R-R interval, and increase in QRS time and heart rate. These changes could be due to the damage of cell membrane in injured cardiac muscle [23]. It has been exposed that a rise in heart rate is responsible for augmented oxygen consumption causing to enhanced necrosis of myocardial tissue [24]. ISO also increased ST-segment voltage and decreased R- wave voltage. This is favorable with the comments of earlier reports. ST-segment elevation reproduces the potential difference in the border between ischemic and non-ischemic regions and consequences in loss of cell membrane function whereas decrease in R-wave voltage might be due to the start of myocardial edema subsequent ISO treatment [25]. Citrus aurantium pre-treatment in ISO treated rats prohibited the pathological changes in the ECG, which suggest s protective effect for its cell membrane. Cardiac muscle contains different diagnostic markers of MI and when heart metabolism injured, it discharges its contents into the extracellular fluid [26]. Cytotoxic enzymes such as CK-MB, LDH, AST, ALT and ALP, which serve as diagnostic markers, could be released from tissues damaged in the circulation due to permeable or disagreement of cell membrane and reflect the changes in plasma membrane integrity [27]. Our data confirmed significant increase in the levels of these enzymatic biomarkers of serum in ISO treated rats, which were in same direction with previous reports. Citrus aurantium pre-co-treatment caused in the dropped activity of the marker enzyme in serum. It validated that citrus aurantium could sustain cell membrane integrity, thereby limiting the leakage of these enzymes. Free radical scavenging enzymes for example SOD, catalase and GP X are the first line of cellular protective system against oxidative stress, excluding reactive oxygen spices ROS such as superoxide and hydrogen peroxide. These enzymes inhibit the formation of more worsening hydroxyl radical. The additional line of guard includes non-enzymatic scavengers such as vitamin C, vitamin E and sulphydryl containing compounds, which hunt remaining free radicals evading decomposition by the antioxidant enzymes [28]. The balance between antioxidant capacity and formation of free radicals is an essential process for the real elimination of oxidative stress in intracellular organelles. Though, in pathological situations similar to MI, the production of ROS can strongly interrupt this equilibrium with an augmented request of the antioxidant protection system [29]. Auto-oxidation induced by ISO can lead to production of massive quantity of ROS, which may attach any type of molecules such as polyunsaturated fatty acids in cell membrane forming peroxyl radicals, producing a chain reaction of lipid peroxidation [29]. This process is an essential pathogenic event in necrosis of myocardial tissue. In the current study, treatment with ISO caused in significant raise in peroxidation of lipids, represented as MDA value, which is in same direction with former reports [26,31]. Citrus aurantium pre-co-treatment displayed an important decrease in the value of serum MDA content which can be related to strong antioxidant capacity of extract against ISO auto-oxidation produced free radicals. Activities of antiperoxidative enzymes SOD and catalase were declined considerably in serum of ISO treated rats. Superoxide dismutase, which catalysis the dismutation of two superoxide radicals to form hydrogen peroxide and molecular oxygen. Therefore, the H 2 O 2 created is deactivated by either catalase or the GSH redox system containing of reduced glutathione as the cofactor for GP X and glutathione reductase [32]. Citrus aurantium pre-co-treatment exhibited a substantial increase in the level of serum SOD and catalase. These enzymes could not alter in the citrus aurantium animal group. In the current study, our data confirms a declined concentration of GSH and GP X in serum of ISO treated rats. GSH, a tripeptide, one of the greatest non-enzymatic antioxidant biomolecules, is existing in the body. GSH has a direct antioxidant role by reacting with superoxide radicals, peroxy radicals and singlet oxygen followed by the creation of oxidized GSH and other disulfides [33]. Diminished activity of these enzymes lead to formation of oxidants and make cardiac myocytes membranes more susceptible to oxidative injury. The current study revealed a significant increase in the value of GSH and activity of GP X in the serum of citrus aurantium pre-co-treated rats. Lipids play a significant role in cardiovascular diseases. A considerable rise in the total cholesterol and triglycerides was detected in serum of ISO treated rats, which is in line with previous reports [15,19]. Rats treated with ISO also exhibited an increase in LDL fraction along with a decline in HDL cholesterol. These alterations could be credited to improved lipid biosynthesis by cardiac cyclic adenosine monophosphate [34]. A sturdy positive correlation has been document among the risk of emerging ischemic heart disease and serum LDL level, while a negative correlation has been stated with HDL-cholesterol [35]. The pre-co-treatment with citrus aurantium effectively restored the elevated triglycerides, LDL-cholesterol and total cholesterol and decreased HDL-cholesterol in the serum of this group. Histopathological investigation of the cardiac muscle tissue in the control rat group represented clear integrity of the cardiac myocytes membrane and no inflammatory cell infiltration was detected. ISO treated rats group showed a cellular dissociative view with marked inflammatory infiltration. The pre-co-treatment with citrus aurantium extract showed reduced inflammatory cell infiltration and relatively normal view of myocardial cells. This confirmed cardio protective effect of hydroalcholic citrus aurantium extract on MI induced by ISO in rats. In conclusion, we can say that the current study confirmed that subcutaneous high-dose injections of isoproterenol can produce MI in rats as evident from the release of myocytes damage markers in serum. Furthermore, provided with experimental evidence, the hydroalcholic citrus aurantium extract preserved antioxidant enzyme levels and enhanced cardiac performance. This conclusion may be a new way to understand the useful effects of citrus aurantium extract on cardio protection against myocardial injury, in which oxidative stress has long been identified to contribute to pathogenesis. The authors are grateful to the Deputy of research and technology of Zahedan University of Medical Sciences for their financial support of research project no The authors acknowledge the department of Physiology and Biochemistry at Zahedan University of Medical Sciences for the support provided for this work. This is an open access article distributed under the terms of the, which permits unrestricted use, distribution, and build upon your work non-commercially. About Us Paper Submission FAQs Testimonials Videos Reprints Pay Online Article Processing Charges Contact Us Sitemap. Home Open Access Journals eBooks Information For Author Article Processing Charges. Publication Ethics. Peer Review System. Behavioral Sciences Food and Nutrition Trends Global Trends in Pharmaceutical Sciences. Home JCCR Cardio protective effects of hydroalcholic citrus aurantium extract on myocardial infarction induced by isoproterenol in male rats. Journal of. Research Article Volume 10 Issue 3. Go to Article Title Abstract Introduction Materials and methods Results Discussion Conclusion Acknowledgement Conflict of Interest References. Chemicals Isoproterenol hydrochloride was purchased from Sigma Aldrich Chemical Company, St. Animals All experiment and procedures defined in this study were approved by the local ethics committee of Zahedan University of Medical Sciences. Experimental design After acclimatization, the animals were allocated randomly into 4 groups 6 in each group. Biochemical analysis After recording the ECG, the animals were sacrificed and blood samples were taken. Plant preparation and extraction Citrus aurantium flowers were taken from Shiraz, Iran, in Statistical analysis Data is expressed as mean ± SE. All values are presented as Mean ± S. During exercise, there is a vagal or parasympathetic withdrawal and, then, there is an upsurge in sympathetic modulation to the heart, revealing a surge in HR and cardiac contractility. Upon cessation of exercise, it is expected that there will be a fast reactivation of vagal modulation, which will provide an abrupt reduction and recovery in HR 6. Recent studies have fixated on examining whether nutritional interventions e. Based on these aforementioned considerations, it was probed as to whether the supplementation of C. aurantium prior to aerobic physical exercise could impact the autonomic control of HR and interfere with cardiovascular recovery following exercise. We assume that C. aurantium would not affect the recovery of cardiovascular and autonomic parameters after exercise. Given these declarations, we intended to assess the effect of C. aurantium supplement on cardiovascular recovery and autonomic constraints after submaximal aerobic exercise. This is a randomized study, double-blind, placebo-controlled crossover clinical trial. According to the Declaration of Helsinki, the intervention protocols were approved by the Research Ethics Committee Institutional—Brazil Process: The register of study details on Clinicaltrials. We recruited 17 male subjects via social media e. to participate in the study. Participants were between 18 and 30 years of age, had a body mass index BMI between Through screening, we studied the presence of some conditions that would make them ineligible to participate in the study, for instance, smoking, present and past anabolic steroid usage, cardiorespiratory, neurological or musculoskeletal disorders, use of pharmacotherapies that affect the autonomic nervous system. At the end of the study, the sample consisted of 12 subjects Figure 1. Additionally, baseline values of heart rate beats per minute , systolic blood pressure SBP , and diastolic blood pressure DBP mmHg were logged Table 1. Table 1. Mean values followed by their respective standard deviations minimum and maximum of age, mass, height, BMI, heart rate, SBP and DBP. The intervention protocols were split into three phases, with an interval of 48—72 h between each protocol to provide time for the participants' physical recovery. On the first day, an initial interview was completed with the participating candidates in the study. After screening, eligible applicants were provided with a list of guidelines to abstain from certain citrus fruits mandarin, sweet, and bitter orange , alcoholic and caffeinated beverages, or nutriments coffee, sports drinks, chewing gum, chocolate , and exercise 24 h prior to the ensuing study sessions. Participants were told to have a light meal e. Through a random sequence, in the second step, participants were randomized to consume a capsule containing mg C. This amount was selected as it is regularly applied in clinical practice In the final stage, the participants received the protocol contrary to the previous one to safeguard the study's crossover. An independent researcher who did not participate in the data logging was responsible for randomizing the interventions, choosing the capsules, and assigning them to the investigator. The capsules were opaque and visibly identical; neither the participant nor the investigator could recognize the capsules' contents. The capsules were attained in commercial form from a reliable provider Florien Fitoativos ® Ltd. Naringin and hesperidin concentrations were not analyzed. The participants persisted for 20 min walking at this speed, and at the end of the activity, the participants were once more seated and monitored for an additional 60 min 8. SBP and BPD measurements were completed indirectly using a stethoscope Littman Classic II, Saint Paul, USA and aneroid sphygmomanometer Welch Allyn Tycos, New York, USA on the participants' left arm For HR and HRV indices scrutiny, cardiac activity was logged beat by beat throughout the data logging technique with a sampling rate of 1 kHz using a Polar ® heart rate monitor model RSCX. The HR and HRV recordings were logged at the following epochs: Rest R1: 90th to 95th min of resting after capsule ingestion , and all through exercise recovery: 0 to 5th min; 5th to 10th min; 15th to 20th min; 25th to 30th min; 35th to 40th min; 45th to 50th min, and; 55th to 60th min Figure 2. Series with regular heartbeats R-R intervals were required to make the HRV indices, as recommended by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology In these series, digital and manual filters were executed to remove artifacts. After collection, the RR intervals were exported to the software program Kubios ® HRV Analysis to produce the linear indices of the frequency domain and time domain Frequency domain analysis was accomplished via spectral analysis by means of the Fast Fourier Transform FFT to cause the high frequency HF index with a sampling rate of 0. The non-linear HRV analysis was achieved using the PyBios ® software Biomedical Signal Analysis in Python Version 1. We dispersed the number of RR intervals through six levels 0—5 , transforming them into a spatial methodology; a sequence of three symbols. All patterns were independently assembled into two clusters, according to the number and type of variation between symbols:. A pilot study conducted with six participants performed the sample size calculation. We applied the root mean square of successive differences between RR intervals in the online software at www. br , which provided the magnitude of the difference. We measured a standard deviation of The Shapiro-Wilk statistical test was enforced to assess data normality. For the cardiovascular recovery and autonomic reactivity analysis during the experimental protocols Rest vs. recovery , One-way analysis of variance ANOVA1 for repeated measures and the Bonferroni post-test was enforced when the assumption of data normality was attained. Friedman's test followed by Dunn's post-test was required for data that did not acquire a normal distribution. Cohen's d calculated effect sizes to measure the magnitude of changes for significant differences. Assessments were achieved using Statistical Package for the Social Sciences SPSS IBM ® SPSS Statistics v. The descriptive data of twelve healthy males that met the study criteria are included in Table 1. These datasets strengthen the homogeneity of our sample. The HR recovery analysis revealed no significant differences between the protocols. In the placebo protocol, the comparison of resting and after exercise established an increase in HR from 0 to 5th min of recovery Rest vs. In the C. aurantium protocol, the same results were attained, and HR values remained significantly enlarged from 0 to 5th min of recovery Rest vs. Table 2. No significant changes were identified in the C. aurantium intervention during the recovery analysis rest vs. recovery for DBP, MAP, and PP. Only SBP demonstrated significant changes in 1 min following exercise Rest vs. aurantium protocol. During the placebo protocol, SBP remained significantly higher during 3 min of recovery compared to rest Rest vs. Table 3. Time and frequency domain indices in addition to non-linear analyzes revealed that autonomic heart rate recovery occurred more quickly in the C. aurantium protocol compared to the placebo protocol. In the placebo protocol, the investigation of recovery rest vs. recovery of the HF index revealed that its values remain depressed throughout 10 min of recording after exercise Rest: Figure 3. In the placebo protocol, pNN50 index values continued to be significantly decreased throughout 20 min of recovery related to resting values Rest: Our findings demonstrate that the ingestion of C. aurantium p-synephrine mg prior to exercise fast-tracks the fall in SBP after physical exertion. Earlier studies propose that one of the benefits of using C. aurantium equated to other adrenergic substances e. Activation of β-3 adrenergic receptors triggers reverse inotropic effects, antagonizing the activation of further classes of adrenoreceptors β-1 and β-2 in cardiac tissue and, thus, decreasing sympathetic modulation to the heart. This clarifies why overall, the binding of p-synephrine with β-3 adrenergic receptors does not increase BP or HR, displaying cardioprotective effects In this study, in the placebo intervention, for the spectral analysis, the HF index, representative of parasympathetic modulation, needed 10 min after termination of exercise to recover. aurantium protocol, we did not find substantial changes in the HF index in exercise recovery vs. Analogous deviations occurred in the pNN50 index and were reduced 20 min after cessation of exercise in the placebo protocol. While in the protocol with C. aurantium , this index continued to be reduced for only 10 min after exercise. aurantium protocol, transformations were only following 5 min of recovery. However, in the C. aurantium protocol, the values were only meaningfully reduced for 5 min after the cessation of exercise. These observations make C. aurantium a safe nutritional compound to be applied during exercise, which supports the recovery of autonomic parameters following exercise. Since a slow post-exercise autonomic recovery is linked with an increased cardiovascular risk 25 , the results of our study indicate that C. aurantium compounds have a potential preventive role on the onset of cardiovascular complications in physical exercise. As caffeine and C. aurantium are frequently sold as complementary formulas for use in humans, preceding studies have assessed the effects of using these substances alone and in combination. Through a randomized clinical trial, Guitiérrez-Hellín et al. aurantium alone or in combination with caffeine would have different results for fat utilization during aerobic physical exercise. No superiority was found between C. aurantium alone and combined with caffeine on the total values of fat consumption during the physical exercise session, while both interventions were superior to the placebo treatment. This supports the isolated use of C. aurantium an alternate way to be applied as an adjunct in cutting body fat without inducing cardiac risk. In the study by Guitiérrez-Hellín et al. aurantium isolated supplement. In contrast, the HR and SBP were significantly higher when caffeine was included in the formulation. Our study achieved no changes for HR, and SBP was lessened more quickly following exercise. The identification of β-3 adrenoreceptors in cardiovascular tissues posed challenges to the paradigm of sympathetic regulation by β-1 and β-2 adrenoceptors. The binding response of p-synephrine to the β-3 receptor may elucidate why no increase in HR or BP is detected when C. aurantium is enforced alone. In contrast, when C. aurantium is combined with caffeine in dietary supplements, it is capable of affecting these parameters, particularly in caffeine-sensitive individuals It has been revealed that the combination of these substances promotes a significant increase in the concentration of plasma catecholamines e. The study by Kliszczewicz et al. aurantium upsurges sympathetic modulation to the heart throughout rest and corroborates the increases in HR and SBP achieved in the study by Guitiérrez-Hellín et al. It is assumed that caffeine alone can increase HR during physical exercise Despite that, a recent meta-analysis demonstrated that caffeine could not delay vagal return to the heart after exercise, evaluated by the HF and root mean square of successive differences between RR intervals RMSSD indices Equally, Kliszczewicz et al. aurantium combined. Caffeine and C. aurantium combination have no extra effects on exercise fat utilization 5. These substances appear to exhibit the opposite cardiovascular effects and, thus, caffeine seems to overlap the beneficial effects of the isolated use of C. aurantium on cardiovascular health. In this study, C. aurantium supplementation alone optimized the recovery of SBP and HRV indices after exercise. The nutritional characteristics demonstrated in the flavonoids e. aurantium perform antioxidant and anti-inflammatory activities, which are partly answerable for accelerating the return of parasympathetic control of heart rate seen by vagal indices of HRV. Such properties can hasten the removal of metabolites produced by physical exercise, restoring baroreflex sensitivity and decreasing metaboreflex activation more quickly at the end of physical exercise While C. aurantium exhibited cardioprotective effects, it is essential to be careful with its usage. Bui et al. Yet, in other studies that enforced doses beneath mg in an acute 5 , 30 , 31 and chronic for 15 days 32 form, no changes were achieved for the HR, SBP, and DBP values, nor electrocardiographic disturbances. Likewise, our results do not support the findings of Bui et al. The results from the study of Ratamess et al. In your results, the p-synephrine supplementation mg did not evoke changes in HR before, during, and following resistance exercise unless mg of caffeine was added to the formulation. The same occur in the rest situation, in another study by Ratamess et al. The study of Bui et al. Although it is a randomized and crossover study, there is a lack of information about allocation order in the study. aurantium, and provoked adjustments in blood pressure, because of higher sweet and fat content e. Furthermore, the authors did not report guarantees that snack was equal on the others evaluation days. Bitter orange caused cardiovascular effect was only observed based on statistical adjustments. A difference was seen compared to placebo but not when compared to baseline. All these factors raise questions about the validity of their conclusions. The results recognized in our analyses will advance health professionals' conduct who work with the prescription of nutritional supplements. Consequently, it may be an alternative way to replace other compounds that demonstrate similar contributions regarding fat utilization during exercise but that promote unwanted cardiovascular effects e. Our study highlights important points about the study population, given that it is restricted to healthy and physically active males. Notwithstanding the number of participants having exceeded the sample size calculation, the final sample is considered small. With the desire to improve body composition. In spite of this, these facts do not allow these results to be extrapolated to other populations and, therefore, further research with obese individuals is needed to confirm the safety of using C. aurantium in combination with exercise. For the time being, we prefer to use a healthy population free from metabolic disorders to prevent possible adverse events from C. aurantium supplementation. Nevertheless, we encourage further studies to be established with C. aurantium as an intervention with these preliminary data. Studies with females and other health conditions should also be performed to increase the external validity of these data and expand the application of C. aurantium promoted the resumption of parasympathetic control and output of sympathetic flow of cardiac rhythm after physical exercise and decreased SBP. Based on these and previous findings, we assume that C. aurantium is a safe nutritional compound with submaximal aerobic exercise in healthy males when used appropriately, moreover, your combination with a good diet there could be improved fat oxidation in exercise without the cardiovascular risk. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. The studies involving human participants were reviewed and approved by University Center of the Juazeiro do Norte Process: CJRB supervised the study, performed experiments, performed the statistical analysis, wrote the introduction, methods, discussion, and results in sections. FJ, ER, and MS collected data and performed conduction of experiments. |
| Related products | Methods: Twelve healthy male adults achieved a crossover, randomized, double-blind, and placebo-controlled trial. We evaluated systolic blood pressure SBP , diastolic blood pressure DBP , pulse pressure PP , mean arterial pressure MAP , heart rate HR and, HR variability indexes at Rest and during 60 min of recovery from exercise. No unfavorable cardiovascular effects were achieved for HR, DBP, PP, and MAP parameters. Conclusions: Citrus aurantium was shown to be safe for the cardiovascular and autonomic systems alongside submaximal aerobic exercise in healthy males. Citrus aurantium L. is a phenylethylamine alkaloid in bitter orange peel, rich in p-synephrine, and abundant in flavonoids 1. p-Synephrine has an adrenergic action and, therefore, the C. aurantium is easily applied in weight loss strategies 2 and, thus, contributes to the restoration of hunger and satiety balance regulation of blood glucose, insulin, and triglycerides 3. P-synephrine has an affinity with β3-adrenergic receptors, seems capable of stimulating lipolysis without compromising cardiovascular activity at rest, unlike other substances e. Recently, Guitiérrez-Hellín et al. aurantium supplementation could elevate fat consumption rates in submaximal aerobic exercise and, therefore, this has made C. aurantium a widely used substance to cut the levels of body fat. Nevertheless, there are no assessments of the cardiovascular safety of C. aurantium in combination with aerobic submaximal exercise, and evidence regarding its use is rare but needed to guide clinical prescriptions that have C. aurantium as a therapeutic option. In this way, the analysis of cardiorespiratory parameters in combination with autonomic control of heart rate HR after physical exercise has been widely enforced to assess cardiovascular risk. Through the scrutiny between heartbeats RR intervals or HR variability HRV , it is possible to study the efferent flow of sympathetic and parasympathetic autonomic to the heart. During exercise, there is a vagal or parasympathetic withdrawal and, then, there is an upsurge in sympathetic modulation to the heart, revealing a surge in HR and cardiac contractility. Upon cessation of exercise, it is expected that there will be a fast reactivation of vagal modulation, which will provide an abrupt reduction and recovery in HR 6. Recent studies have fixated on examining whether nutritional interventions e. Based on these aforementioned considerations, it was probed as to whether the supplementation of C. aurantium prior to aerobic physical exercise could impact the autonomic control of HR and interfere with cardiovascular recovery following exercise. We assume that C. aurantium would not affect the recovery of cardiovascular and autonomic parameters after exercise. Given these declarations, we intended to assess the effect of C. aurantium supplement on cardiovascular recovery and autonomic constraints after submaximal aerobic exercise. This is a randomized study, double-blind, placebo-controlled crossover clinical trial. According to the Declaration of Helsinki, the intervention protocols were approved by the Research Ethics Committee Institutional—Brazil Process: The register of study details on Clinicaltrials. We recruited 17 male subjects via social media e. to participate in the study. Participants were between 18 and 30 years of age, had a body mass index BMI between Through screening, we studied the presence of some conditions that would make them ineligible to participate in the study, for instance, smoking, present and past anabolic steroid usage, cardiorespiratory, neurological or musculoskeletal disorders, use of pharmacotherapies that affect the autonomic nervous system. At the end of the study, the sample consisted of 12 subjects Figure 1. Additionally, baseline values of heart rate beats per minute , systolic blood pressure SBP , and diastolic blood pressure DBP mmHg were logged Table 1. Table 1. Mean values followed by their respective standard deviations minimum and maximum of age, mass, height, BMI, heart rate, SBP and DBP. The intervention protocols were split into three phases, with an interval of 48—72 h between each protocol to provide time for the participants' physical recovery. On the first day, an initial interview was completed with the participating candidates in the study. After screening, eligible applicants were provided with a list of guidelines to abstain from certain citrus fruits mandarin, sweet, and bitter orange , alcoholic and caffeinated beverages, or nutriments coffee, sports drinks, chewing gum, chocolate , and exercise 24 h prior to the ensuing study sessions. Participants were told to have a light meal e. Through a random sequence, in the second step, participants were randomized to consume a capsule containing mg C. This amount was selected as it is regularly applied in clinical practice In the final stage, the participants received the protocol contrary to the previous one to safeguard the study's crossover. An independent researcher who did not participate in the data logging was responsible for randomizing the interventions, choosing the capsules, and assigning them to the investigator. The capsules were opaque and visibly identical; neither the participant nor the investigator could recognize the capsules' contents. The capsules were attained in commercial form from a reliable provider Florien Fitoativos ® Ltd. Naringin and hesperidin concentrations were not analyzed. The participants persisted for 20 min walking at this speed, and at the end of the activity, the participants were once more seated and monitored for an additional 60 min 8. SBP and BPD measurements were completed indirectly using a stethoscope Littman Classic II, Saint Paul, USA and aneroid sphygmomanometer Welch Allyn Tycos, New York, USA on the participants' left arm For HR and HRV indices scrutiny, cardiac activity was logged beat by beat throughout the data logging technique with a sampling rate of 1 kHz using a Polar ® heart rate monitor model RSCX. The HR and HRV recordings were logged at the following epochs: Rest R1: 90th to 95th min of resting after capsule ingestion , and all through exercise recovery: 0 to 5th min; 5th to 10th min; 15th to 20th min; 25th to 30th min; 35th to 40th min; 45th to 50th min, and; 55th to 60th min Figure 2. Series with regular heartbeats R-R intervals were required to make the HRV indices, as recommended by the Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology In these series, digital and manual filters were executed to remove artifacts. After collection, the RR intervals were exported to the software program Kubios ® HRV Analysis to produce the linear indices of the frequency domain and time domain Frequency domain analysis was accomplished via spectral analysis by means of the Fast Fourier Transform FFT to cause the high frequency HF index with a sampling rate of 0. The non-linear HRV analysis was achieved using the PyBios ® software Biomedical Signal Analysis in Python Version 1. We dispersed the number of RR intervals through six levels 0—5 , transforming them into a spatial methodology; a sequence of three symbols. All patterns were independently assembled into two clusters, according to the number and type of variation between symbols:. A pilot study conducted with six participants performed the sample size calculation. We applied the root mean square of successive differences between RR intervals in the online software at www. br , which provided the magnitude of the difference. We measured a standard deviation of The Shapiro-Wilk statistical test was enforced to assess data normality. For the cardiovascular recovery and autonomic reactivity analysis during the experimental protocols Rest vs. recovery , One-way analysis of variance ANOVA1 for repeated measures and the Bonferroni post-test was enforced when the assumption of data normality was attained. Friedman's test followed by Dunn's post-test was required for data that did not acquire a normal distribution. Cohen's d calculated effect sizes to measure the magnitude of changes for significant differences. Assessments were achieved using Statistical Package for the Social Sciences SPSS IBM ® SPSS Statistics v. The descriptive data of twelve healthy males that met the study criteria are included in Table 1. These datasets strengthen the homogeneity of our sample. The HR recovery analysis revealed no significant differences between the protocols. In the placebo protocol, the comparison of resting and after exercise established an increase in HR from 0 to 5th min of recovery Rest vs. In the C. aurantium protocol, the same results were attained, and HR values remained significantly enlarged from 0 to 5th min of recovery Rest vs. Table 2. No significant changes were identified in the C. aurantium intervention during the recovery analysis rest vs. recovery for DBP, MAP, and PP. Only SBP demonstrated significant changes in 1 min following exercise Rest vs. aurantium protocol. During the placebo protocol, SBP remained significantly higher during 3 min of recovery compared to rest Rest vs. Table 3. Time and frequency domain indices in addition to non-linear analyzes revealed that autonomic heart rate recovery occurred more quickly in the C. aurantium protocol compared to the placebo protocol. In the placebo protocol, the investigation of recovery rest vs. recovery of the HF index revealed that its values remain depressed throughout 10 min of recording after exercise Rest: Figure 3. In the placebo protocol, pNN50 index values continued to be significantly decreased throughout 20 min of recovery related to resting values Rest: Our findings demonstrate that the ingestion of C. aurantium p-synephrine mg prior to exercise fast-tracks the fall in SBP after physical exertion. Earlier studies propose that one of the benefits of using C. aurantium equated to other adrenergic substances e. Activation of β-3 adrenergic receptors triggers reverse inotropic effects, antagonizing the activation of further classes of adrenoreceptors β-1 and β-2 in cardiac tissue and, thus, decreasing sympathetic modulation to the heart. This clarifies why overall, the binding of p-synephrine with β-3 adrenergic receptors does not increase BP or HR, displaying cardioprotective effects In this study, in the placebo intervention, for the spectral analysis, the HF index, representative of parasympathetic modulation, needed 10 min after termination of exercise to recover. aurantium protocol, we did not find substantial changes in the HF index in exercise recovery vs. Analogous deviations occurred in the pNN50 index and were reduced 20 min after cessation of exercise in the placebo protocol. While in the protocol with C. aurantium , this index continued to be reduced for only 10 min after exercise. aurantium protocol, transformations were only following 5 min of recovery. However, in the C. aurantium protocol, the values were only meaningfully reduced for 5 min after the cessation of exercise. These observations make C. aurantium a safe nutritional compound to be applied during exercise, which supports the recovery of autonomic parameters following exercise. Since a slow post-exercise autonomic recovery is linked with an increased cardiovascular risk 25 , the results of our study indicate that C. aurantium compounds have a potential preventive role on the onset of cardiovascular complications in physical exercise. As caffeine and C. aurantium are frequently sold as complementary formulas for use in humans, preceding studies have assessed the effects of using these substances alone and in combination. Through a randomized clinical trial, Guitiérrez-Hellín et al. aurantium alone or in combination with caffeine would have different results for fat utilization during aerobic physical exercise. No superiority was found between C. aurantium alone and combined with caffeine on the total values of fat consumption during the physical exercise session, while both interventions were superior to the placebo treatment. This supports the isolated use of C. aurantium an alternate way to be applied as an adjunct in cutting body fat without inducing cardiac risk. In the study by Guitiérrez-Hellín et al. aurantium isolated supplement. In contrast, the HR and SBP were significantly higher when caffeine was included in the formulation. Our study achieved no changes for HR, and SBP was lessened more quickly following exercise. The identification of β-3 adrenoreceptors in cardiovascular tissues posed challenges to the paradigm of sympathetic regulation by β-1 and β-2 adrenoceptors. The binding response of p-synephrine to the β-3 receptor may elucidate why no increase in HR or BP is detected when C. aurantium is enforced alone. In contrast, when C. aurantium is combined with caffeine in dietary supplements, it is capable of affecting these parameters, particularly in caffeine-sensitive individuals It has been revealed that the combination of these substances promotes a significant increase in the concentration of plasma catecholamines e. The study by Kliszczewicz et al. aurantium upsurges sympathetic modulation to the heart throughout rest and corroborates the increases in HR and SBP achieved in the study by Guitiérrez-Hellín et al. It is assumed that caffeine alone can increase HR during physical exercise Despite that, a recent meta-analysis demonstrated that caffeine could not delay vagal return to the heart after exercise, evaluated by the HF and root mean square of successive differences between RR intervals RMSSD indices Equally, Kliszczewicz et al. aurantium combined. Caffeine and C. aurantium combination have no extra effects on exercise fat utilization 5. These substances appear to exhibit the opposite cardiovascular effects and, thus, caffeine seems to overlap the beneficial effects of the isolated use of C. aurantium on cardiovascular health. In this study, C. aurantium supplementation alone optimized the recovery of SBP and HRV indices after exercise. The nutritional characteristics demonstrated in the flavonoids e. aurantium perform antioxidant and anti-inflammatory activities, which are partly answerable for accelerating the return of parasympathetic control of heart rate seen by vagal indices of HRV. Such properties can hasten the removal of metabolites produced by physical exercise, restoring baroreflex sensitivity and decreasing metaboreflex activation more quickly at the end of physical exercise While C. aurantium exhibited cardioprotective effects, it is essential to be careful with its usage. Bui et al. Yet, in other studies that enforced doses beneath mg in an acute 5 , 30 , 31 and chronic for 15 days 32 form, no changes were achieved for the HR, SBP, and DBP values, nor electrocardiographic disturbances. Likewise, our results do not support the findings of Bui et al. The results from the study of Ratamess et al. In your results, the p-synephrine supplementation mg did not evoke changes in HR before, during, and following resistance exercise unless mg of caffeine was added to the formulation. The same occur in the rest situation, in another study by Ratamess et al. The study of Bui et al. Although it is a randomized and crossover study, there is a lack of information about allocation order in the study. aurantium, and provoked adjustments in blood pressure, because of higher sweet and fat content e. Furthermore, the authors did not report guarantees that snack was equal on the others evaluation days. Bitter orange caused cardiovascular effect was only observed based on statistical adjustments. A difference was seen compared to placebo but not when compared to baseline. All these factors raise questions about the validity of their conclusions. The results recognized in our analyses will advance health professionals' conduct who work with the prescription of nutritional supplements. Consequently, it may be an alternative way to replace other compounds that demonstrate similar contributions regarding fat utilization during exercise but that promote unwanted cardiovascular effects e. It delivers the protective phytonutrients of the Mediterranean diet in a tailor-made optimized blend for support of cardiovascular health. References 1. Sánchez Macarro, M. et al, Nutrients This site uses cookies as described in our Privacy Statement and Cookie Policy. To see what cookies we use and set your own preferences, please refer to the Statement and Policy. Otherwise, if you agree to our use of cookies, please continue to use our site. Ginseng Highly authenticated and purified ginseng. Green Mate Natural appetite and metabolism support. Sharp-PS® A natural nutrient for body and mind. AB-Fortis® Microencapsulated iron. Chamomile Natural immune, stress and digestive support. Ginkgo Pure, natural cognitive support. Green tea Hyperpure Green Tea. Neuravena® Natural support for brain function. FenuLife® A unique soluble fiber. Litesse® Specialty carbohydrate for digestive health. BetaPower® Natural betaine. Grow Nutrients® Nutrients with superior absorption and assimilation into the body. Guarana Natural caffeine. Echinacea Dry pressed juice from Echinacea purpurea. Go-Less® Bladder wellness support in men and women. Go-Less® Men Natural support for male urinary health. LinumLife® Natural source of flax lignans. SoyLife Soy germ ingredient rich in daidzein. Benolea® Natural blood pressure support. BroccoRaphanin® Stimulates detoxification. 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| Supports cardiovascular health | Silva LEV, Fazan R Jr, Marin-Neto JA. Eur J Pharmacol Mean Arterial Pressure. Content provided by KLK OLEO Jan Product Brochure. Citation: Stohs SJ, Preuss HG, Shara M. |
| Bitter orange extract may raise blood pressure and heart rate: FDA analysis | The amount of time it takes to recover from weight loss surgery depends on the type of surgery and surgical technique you receive. Compounds and nutrients. Dragull K, Breksa AP, Cain B. Otherwise, if you agree to our use of cookies, please continue to use our site. These observations make C. |
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