Methods Sixteen patients with COPD were divided into an aerobic (continuous and interval) training group (AT) (n=10) and a control group (CG) (n=6). An incremental test (initial speed of 2.0 kmh −1, constant slope of 3%, and increments of 0.5 kmh −1 every 2 minutes) was performed. The training group underwent training for 4 weeks at 60% of the peak velocity reached in the incremental test (vVO 2peak) (50 minutes of continuous effort), followed by 4 weeks of sessions at 75% of vVO 2peak (30 minutes of continuous effort), and 4 weeks of interval training (5×3-minute effort at vVO 2peak, separated by 1 minute of passive recovery). Intensities were adjusted through an incremental test performed at the end of each period. Introduction Although various training modalities can be applied in patients with chronic obstructive pulmonary disease (COPD) (eg, resistance, in-water, and tai chi), aerobic stimulus has been investigated in several studies, predominantly due to the ease of application, prescription and, consequently, monitoring of this training modality.
Evaluation of pharmacodynamic properties and safety of Cinnamomum zeylanicum (Ceylon cinnamon) in healthy adults: a phase I clinical trial Priyanga Ranasinghe 1 Email author View ORCID ID profile, Ranil Jayawardena 2.
Aerobic training provides clear improvement in the quality of life and increases in aerobic parameters and functional capacity, thereby improving factors such as dyspnea, exercise intolerance, and reduced quality of life, which are common symptoms in patients with COPD.– Mucociliary clearance is deficient in patients with COPD, mainly due to mucus hypersecretion, which is related to a significant decrease in forced expiratory volume in the first second and severe coughing. This situation increases the risk of hospitalization. Improvements in mucociliary clearance have been observed after acute aerobic stimulus, but the chronic effects are still controversial in healthy individuals., Although knowledge about the response of mucociliary clearance to aerobic stimulus appears to be extremely important, no studies have investigated this parameter longitudinally in patients with COPD. Aerobic training has been related to significant improvements in autonomic modulation, suggesting better adaptation and efficiency of the cardiovascular system., In addition, relations between autonomic control and aerobic variables were also observed acutely in COPD patients, highlighting that good aerobic conditioning is related to an increase in the vagal activity of heart rate control.
However, the possible effects of different aerobic models on autonomic control remain unclear. In this context, aerobic training in patients with COPD can be performed with continuous or interval efforts., Continuous efforts are frequently applied 3–4 times per week, with different intensities and durations, whereas interval training sessions are applied 2–3 times per week, using effort periods lasting 30–180 seconds, separated by passive or active recovery. When these aerobic training modalities (ie, continuous and interval) are applied separately, the training adaptations appear to be similar in patients with COPD.
Moreover, to our knowledge, no studies have investigated the use of continuous and interval sessions in the same periodization in patients with COPD. This approach may be more effective, principally by enabling the adaptations related to both models of aerobic training stimulus (ie, continuous and interval). In summary, aerobic exercise can be considered a good intervention in pulmonary rehabilitation, but more studies on mucociliary clearance responses and autonomic control adaptations from aerobic training are necessary, specifically when training is applied with continuous and interval stimulus in the same periodization. Thus, the aim of this study was to investigate the effects of a 12-week aerobic training protocol with continuous and interval sessions on autonomic modulation, mucociliary clearance, and aerobic parameters in patients with COPD. Setting and participants This study was characterized as a nonrandomized clinical trial which considered the effects of 12 weeks of aerobic training on autonomic modulation (evaluated through heart rate variability HRV), mucociliary clearance, and aerobic function in patients with COPD, according to the criteria established by the Global Initiative for Obstructive Lung Disease (GOLD).
Flow diagram showing the participation of the patients in the study. Medications used by the patients during the study were: β 2 agonists (n=12), anticholinergics (n=6), diuretics (n=4), antagonists of angiotensin receptors (n=5), β-blockers (n=1), benzodiazepines (n=1). All participants were previously informed about the procedures and aims of this study, and signed a consent form. All procedures utilized in this study were approved by the Institutional Ethics Research Committee (CAAE: 01114912.0.0000.5402).
Design overview The experimental protocol consisted of patient identification, anthropometric evaluation, pulmonary function through spirometry, a cardiopulmonary test, evaluation of autonomic function by HRV, a mucociliary clearance test using the saccharin transit time (STT) test, and realization of 12 weeks of aerobic training. The participants were conventionally divided into AT and no-training CG. Evaluation periods were performed at baseline (M0) and after 12 weeks (M1) for both groups. To minimize interference with circadian rhythm and external factors, evaluations were individually performed in a room with temperature ranging from 21°C to 23°C and relative humidity between 50% and 60%, always in the morning period between 8 am and 12 pm.
Final assessments were performed between 24 and 48 hours after the final training session. For all sessions, patients were instructed to: 1) avoid consuming caffeine for 24 hours before procedures; 2) eat a light meal 2 hours before the tests; 3) avoid drinking alcoholic beverages for at least 4 hours; 4) avoid strenuous physical exercises the day prior to the session; and 5) wear suitable and comfortable clothes for physical exercises. Evaluation of aerobic function For the prescription of aerobic exercise and evaluation of aerobic function, patients performed a maximal cardiopulmonary exercise test (Inbrasport ATL 2000; Inbrasport, Rio Grande do Sul, Brazil) with an initial speed of 2.0 kmh −1, constant slope of 3%, and increments of 0.5 kmh −1 every 2 minutes. The test was performed until voluntary exhaustion was reached. None of the patients presented clinical or electrocardiographic changes that prevented them from finishing the test. The cardiopulmonary test was repeated every 4 weeks in order to adjust session intensity. The following variables were monitored continuously: 1) heart rate (Polar S810i, Polar Electro, Kempele, Finland); 2) arterial oxygen saturation (SpO 2%) (Mindray PM 50 Oximeter, Mindray, Sao Paulo, Brazil); and 3) subjective perception of effort.
Furthermore, ventilatory variables were obtained through the gas analyzer (VO2000, Medical Graphics, St. Paul, MN, USA), which was calibrated before every test according to the supplier’s specifications.
The flow of average air was utilized in all tests, and gas samples were obtained every 10 seconds (Aerograph ®, MI, USA). The peak oxygen uptake (VO 2peak) was considered the highest oxygen consumption average of the final 30 seconds of the exercise (VO 2). The speed related to VO 2peak (vVO 2peak) was considered to be the highest intensity reached during the test. In cases where the patient demonstrated exhaustion before the end of the stage, the vVO 2peak was adjusted by the equation proposed by Kuipers et al. Moreover, the gas exchange threshold (GET) was determined using the V-Slope method, described by Sue et al for COPD patients. In the present study, the breakpoint of the VCO 2–VO 2 relationship was assumed as the GET, observed during the incremental test. Evaluation of autonomic modulation For the HRV analysis, heart rate was captured beat by beat through a heart rate monitor, Polar S810i (Polar Electro), which had been properly validated.
After explaining the necessary procedures for data collection, an elastic strap was positioned on the chest of each patient at the xiphoid process, and a heart rate receiver was placed on the wrist (Polar Electro). Heart rate at rest was recorded for 20 minutes with the patient in a seated position. For the analysis of HRV indexes, 256 consecutive RR intervals were used. They were selected from the most stable portion and, in order to eliminate premature ectopic beats and artifacts, were submitted to digital filtering through Polar Precision Performance SW Software (version 4.01.029) supplemented by manual procedures. Only series with more than 95% sinus beats were included in this study., Indexes in the time and frequency domains were calculated. Evaluation of nasal mucociliary clearance For mucociliary clearance evaluation, the patients were seated with their heads in a straight position at 10°. The STT started with the introduction of 2.5 mg of granulated saccharin sodium through a plastic straw, under visual control, 2 cm into the right nostril.
At this moment, the timer was started, and patients were instructed not to walk, talk, cough, sneeze, scratch, or blow their nose. They were also instructed to swallow as little as possible until they could feel the flavor in their mouth. At this point, the patient advised the examiner, who then registered the time.– For the STT at baseline condition, the patients remained at rest for 20 minutes before starting the test in order to minimize the effects of the external environment on the nasal ciliary beat. Periodized aerobic training All sessions were performed on a treadmill (Inbrasport ATL 2000, Porto Alegre, Brazil). The aerobic training was composed of three training mesocycles, each lasting 4 weeks. The frequency of the sessions was three times per week.
The training sessions were divided into three intensity zones: Z1: 50-minute sessions at an intensity corresponding to 60% of vVO 2peak (continuous effort); Z2: 30-minute sessions at an intensity corresponding to 75% of vVO 2peak (continuous effort); and Z3: formed by five efforts of 3 minutes performed at 100% of vVO 2peak, separated by 1 minute of passive recovery (interval effort). The intensity of each mesocycle was adjusted according to the incremental test performed every 4 weeks. The first training mesocycle predominated in the sessions Z1 (85.9% of total sessions; 344 minutes), with a shorter time in Z2 (14.1% of total sessions; 57 minutes). In the second mesocycle, sessions were applied in Z1 (34.5% of total sessions; 138 minutes), but the predominance was in Z2 (65.5% of total volume; 262 minutes). The third mesocycle had sessions in Z2 (32.5% of total volume; 130 minutes) with predominance in Z3 (67.5% of total volume; 270 minutes).
Thus, COPD patients performed 1091 minutes of aerobic training. The intensity and different session durations between mesocycles were chosen on the basis of previously published studies.– demonstrates the time spent in each intensity zone during the 12-week aerobic training protocol. Statistical analysis Initially, the analysis of data normality was performed and certified by the Shapiro–Wilk test. Asymmetric distribution was observed for VO 2peak, normalized by weight (M0 in both AT and CG; P. Abbreviations: AT, aerobic training group; CG, control group; BMI, body mass index; FEV 1, forced expiratory volume in the first second; FVC, forced vital capacity; (%pred), percentage of predicted values. Demonstrates the aerobic parameters observed at M0 and M1 for both groups. No significant differences were observed between the AT and the CG at M0 ( P0.37).
All aerobic variables increased significantly after 12 weeks for the AT group ( P0.21). At M1, the AT group presented higher values compared to the CG for VO 2peak (absolute and relative to weight values; P=0.02 and 0.01, respectively), vVO 2peak ( P=0.04), and VO 2 observed at GET ( P=0.01). Abbreviations: VO 2peak, peak oxygen uptake; vVO 2peak, velocity corresponding to VO 2peak; GET, gas exchange threshold. Shows the results of autonomic modulation evaluation in the time and frequency domains.
No differences between groups were observed at M0 ( P0.71). An increase in the HF (ms) index after 12 weeks can be observed in the AT ( P=0.042). However, although a tendency was observed for RMSSD ( P=0.08), there was no difference for the other HRV parameters ( P0.13) in the AT group. No significant differences were observed in the CG ( P0.31). Moreover, no differences were observed between the groups at M1 ( P0.08).
Abbreviations: SDNN, standard deviation of the mean of all normal RR intervals; RMSSD, root mean square of differences between adjacent normal RR intervals in a time interval; LF, spectral component of low frequency; HF, spectral component of high frequency; nu, normalized units. Shows the values of STT between the groups at M0 and M1. No differences were observed between the groups at M0 ( P=0.61). In addition, no changes were observed during 12 weeks either in the AT ( P=0.94) or in the CG ( P=0.69) group. Values were similar between the groups at M1 ( P=0.12).
Discussion The main findings of this study demonstrate that 12 weeks of aerobic training applied with continuous and interval sessions induced a significant increase in aerobic parameters obtained through an incremental test. Moreover, a positive influence on autonomic modulation was observed, evidenced by a significant increase in parasympathetic modulation.
However, no improvement was observed in the STT after aerobic training. VO 2peak is considered an index of maximum aerobic power, while vVO 2peak can be seen as the index that better represents the association between aerobic power and movement economy. GET is an important submaximal aerobic variable, mainly because it represents the highest intensity where lactate presents equilibrium in the blood. In addition, this index is frequently used in training prescription, monitoring, and performance prediction., Several studies have demonstrated improvement in these parameters after execution of aerobic training,– which is essential in all COPD stages due to its capacity to reduce dyspnea, improve functional capacity, and offer better quality of life for these patients., In this study, an important improvement in all aerobic variables was observed after the aerobic training. Although on a smaller scale, a similar response was found in studies that applied traditional training methods.,– It was also observed that after 12 weeks of aerobic training, there was a significant increase in HF (ms), which represents the parasympathetic component of autonomic modulation. In relation to other evaluated indices, no significant difference was observed before or after training. However, it was observed that HF (nu) increased after 12 weeks in the AT and the LF (nu) index was reduced in relation to the LF/HF ratio, representing an increase in parasympathetic activity, a reduction in sympathetic activity, and an improvement in the sympathetic–vagal balance.
These data indicate that there was a positive impact on autonomic modulation in patients submitted to periodized aerobic training, suggesting better adaptation and efficiency of the cardiovascular system in these patients, considering the environmental and physiological stimulus required at every moment of daily life activities. This includes better respiratory capacity and performance responses during physical activity, which is essential to the rehabilitation process in the COPD population. Previous studies have also shown significant improvements in autonomic modulation after completion of physical training in patients with COPD. Camillo et al applied a protocol of aerobic resistance training combined with high intensity, after which a significant increase in the RMSSD index was observed, with no changes in the spectral indices. Borghi-Silva et al after a 6-week aerobic training protocol, obtained significant increases in the RMSSD index, a decrease in LF, and an increase in HF, analyzed in normalized units.
A high level of aerobic fitness has been associated with HRV, probably due to increased vagal activity in controlling the heart rate., In relation to mucociliary clearance, there was no significant difference between periods. This finding corroborates the results found by Salzano et al who concluded that aerobic training did not significantly affect mucociliary clearance. The study only demonstrated an acute effect, ie, an increase in mucociliary activity 15 minutes after the aerobic exercise, which can be correlated with increased ventilation and autonomic nervous system activity during the execution of exercise. Nevertheless, this increase was not sustained when analyzed 75 minutes after the training, when it was observed that STT had returned to values close to the initial values. The chronic effects of aerobic training on mucociliary clearance in patients with COPD are still not well established in the literature.
Salh et al conducted a study in lung disease patients with cystic fibrosis submitted to aerobic training on an ergometer cycle, and analyzed the quantity of mucus expectoration, which is directly related to mucociliary activity and clearance, after 2 months of home physical training. The results demonstrated weight increases in the collected mucus, although not a significant amount. The results shown by Salh et al were similar to those in the present study as it was not possible to observe any influence of aerobic training on mucociliary clearance in patients with COPD.
Previous studies have demonstrated that patients with COPD presented loss and significant alterations in mucociliary clearance., Afonso et al found that the mucus relative velocity of ciliary transport on frog palate was greater in the healthy individuals than in the COPD and bronchiectasis groups: healthy group =1.0±0.19 seconds, COPD group =0.91±0.17 seconds, and bronchiectasis group =0.76±0.23 seconds. In contrast, such alterations were not detected in the present study, where patients presented preserved mucociliary function with normal baseline values. It is suggested that these levels are associated with the smoking cessation period of these patients, who were included in this study only after 1 year of smoking abstinence; the patients presented a mean time of 9.5 years without smoking. It is known that there is repair and remodeling of the tissue of the respiratory tract in patients with COPD, although mechanisms for such restructuring are still not clear. Ramos et al found that there is reversibility of mucociliary function in smokers 15 days after smoking abstinence.
It is believed that similar mechanisms also occur in patients with COPD. Therefore, smoking cessation is of the utmost importance as a fundamental component of pulmonary rehabilitation programs. The present proposal of linear periodized aerobic training resulted in significant aerobic improvements, in addition to positively influencing autonomic modulation in patients with COPD. This enriches and provides additional support to discussions on the theme of training modalities for these individuals. Furthermore, the present training proposal consisted of an additional option when compared to other COPD training methods, as it allowed better adaptation of the neuromuscular system to support the burdens imposed by the variations in volume and training intensities. In this way, it differentiates itself from pulmonary rehabilitation programs widely recommended as part of COPD treatment.
Limitations In contrast to previous studies, the aerobic training applied was composed of both continuous and interval sessions. This approach was predominantly chosen because we expected lower levels of monotony due to the decrease in time expended in each zone of training (ie, Z1: “easy” continuous; Z2: “hard” continuous; Z3: “heavy” interval). Thus, we believe that this study contributes to the training prescription applied to COPD patients. However, the main limitation was the high loss of participants in both groups during the experiment, which highlights the need for more studies using this aerobic training prescription.
Methods This phase I clinical trial was conducted at the Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka. Thirty healthy adults were recruited for the study, conducted for a period of 3 months, with the dose of CZ (water extract) increased at monthly intervals (85 mg, 250 mg and 500 mg). Data collection was carried out at baseline and during each monthly follow up visit. Anthropometric, clinical and biochemical assessments were done at baseline and during follow up. Adverse effects and drug compliance was also evaluated. Results Twenty eight subjects completed the three months follow up. Mean age was 38.8 ± 10.4 years and 50% were males.
There were no significant changes in the anthropometric parameters during the three months follow up. Both systolic and diastolic blood pressure reduced significant during the 1st month and this reduction was sustained throughout follow up.
Full blood count, renal function tests, liver function tests, fasting blood glucose, HDL-c, VLDL-d and triglycerides remained within the normal range without any significant alteration during the 3 months. A significant reduction in the TC ( p. Cinnamon, the inner bark of a tropical evergreen tree has two main varieties, Cinnamomum cassia ( Cinnamomum aromaticum) and Cinnamomum zeylanicum (CZ).
In Ayurvedic medicine Cinnamon is considered as a treatment for many ailments, including those of the respiratory, digestive and gynecological systems. Cinnamomum zeylanicum, also known as Ceylon cinnamon (the source of its Latin name, zeylanicum) or ‘true cinnamon’ is indigenous to Sri Lanka and Southern parts of India. Sri Lanka (formerly known as Ceylon) produces the largest quantity and the best quality CZ. Preparation of cinnamon involves stripping of the outer bark of the tree and letting the inner bark to dry and curl up into its customary cinnamon quills, it is available in the market either in its whole quill form (Cinnamon sticks) or as ground powder.
At present both Cinnamon cassia and CZ are sold as preventative/therapeutic supplements for many ailments including, metabolic syndrome, insulin resistance, type 2 diabetes, hyperlipidaemia and arthritis. It is marketed either as a tablet/capsule or as different items of food fortified with cinnamon, including cinnamon biscuits, tea and sweets. One important difference between ‘true’ cinnamon and the cassia cinnamon is their coumarin content. The coumarin content in CZ appears to be very small to cause health risks, whereas the coumarin level in Cinnamomum aromaticum appears to be much higher and may pose health risks if consumed in higher quantity on a regular basis. The usage of Cassia cinnamon as a regular supplement with meals was not advocated or the daily dosage was restricted in many countries due to the toxic effects of Cinnamomum aromaticum on the liver and coagulation.
In contrast CZ has shown to contain a lesser content of coumarin , , and thus it may be possible that CZ could be used in higher doses without toxic effects for longer durations. A recent systematic review summarized the medicinal properties of CZ. The authors concluded that, the available in-vitro and in-vivo evidence suggests that CZ has anti-microbial, anti-parasitic, anti-oxidant and free radical scavenging properties. In addition the authors also indicated that CZ seems to lower blood glucose, serum cholesterol and blood pressure, suggesting beneficial cardiovascular effects.
However they noted the absence of properly conducted randomized controlled human trials, to decide on efficacy and safety of long term CZ use in humans and to determine whether these effects have public health implications. Animal studies on CZ has not demonstrated any significant adverse effects or toxicity on the liver, kidney and the pancreas. However, it is necessary to conduct well planned safety studies in humans, prior to advocating regular use of CZ for any medicinal benefit. This is also required prior to the conduct of medium-long term Randomized Controlled Phase II/III Clinical Trials evaluating the medicinal claims of CZ in humans with disease. The present study aims to evaluate the Pharmacodynamic properties and Safety of CZ in Healthy adults using a Phase I Clinical Trial design. Study population and sampling This phase I clinical trial was conducted at the Department of Pharmacology, Faculty of Medicine, University of Colombo, Sri Lanka. The study was approved by the Ethics Review Committee of Faculty of Medicine, University of Colombo, Sri Lanka (EC/12/157) and registered at the Sri Lanka Clinical Trials Registry (SLCTR/2013/001).
The clinical trial was conducted in compliance with the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines. Thirty healthy adults were recruited for the study, based upon inclusion and exclusion criteria (defined below). Sample size for this phase I clinical trial was determined as per the recommendations of the Center for Drug Evaluation and Research at the Food and Drug Administration. The clinical trial was conducted for a period of 3 months, with the dose of CZ increased at monthly intervals. Subjects were initially contacted by open advertisement and informed written consent was obtained from all participants prior to recruitment for the study.
Data collection was carried out by trained medical research assistants, using a standardized case record form, at baseline (Visit ‘0) and during each monthly follow up visit (Visit ‘1’, ‘2′ and ‘3′). Initially a brief history was taken from each patient, which included symptoms related to any disease, subsequently a physical examination was carried out, which included the measurement of body temperature, examination of the systems (respiratory, cardiovascular, abdomen and nervous system). Cardiovascular examination included the measurement of blood pressure (SBP and DBP) and pulse (rate, rhythm and volume).
Subsequently anthropometric measurements were carried out, which included the measurement of the height, weight, waist and hip circumferences. The following biochemical assessments were done at baseline, at the stated intervals and on completion of the study (Table ); FBG, total cholesterol TC, triglycerides, LDL cholesterol, HDL cholesterol, liver function tests (AST, ALT, PT/INR and serum bilirubin), renal function tests (serum creatinine), urine analysis (UFR) and FBC (white cell count, haemoglobin and platelet count).
Furthermore, any adverse events which occurred during the preceding month were also noted during these visits. Drug compliance of patients was evaluated by pill counting (number of pill’s returned monthly). Subjects are asked to return remaining drugs and their compliance will be evaluated by using the formula given below. Atotal cholesterol, triglyceride, HDL cholesterol; bAST, ALT, total bilirubin, PT/INR; ccreatinine; dWBC, RBC, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT); ebody weight (kg), height (cm), waist circumference (cm), hip circumference (cm), waist:hip ratio; fUrine microscopy, urine for sugar and protein The details of items which will be measured at every visit are described in Table. Anthropometric and blood pressure measurements Body weight was measured using a calibrated electronic floor scale (SECA 815 by SECA GmbH & Co. Hamburg, Germany) to the nearest 0.1 kg. Height was measured to the nearest 0.1 cm using an upright plastic portable Stadiometer (SECA 217 by SECA GmbH & Co.
Hamburg, Germany). BMI was calculated as weight (in kilograms) divided by the square of height (in meters). Waist circumference (WC) was measured with a non-elastic tape (SECA 203 by SECA GmbH & Co.
Hamburg, Germany) at a point midway between the lower border of the rib cage and the iliac crest at the end of normal expiration. Similarly, the hip circumference was also measured at widest part of the buttocks in the inter-trochantric level to the nearest 0.1 cm. All anthropometric measurements were made by using standard equipment and following WHO guidelines.
Seated blood pressure (SBP and DBP) was measured after a 10-min rest with Omron IA2 digital blood pressure monitors (Omron Healthcare, Singapore). Biochemical and statistical analysis Biochemical tests were performed in the laboratory of the Department of Pharmacology, Faculty of Medicine, University of Colombo. Glucose assay was performed by enzymatic colorimetric (glucose oxidase) method in RxDaytona™ chemical analyzer (Randox Laboratories LTD, Antrim, UK). Total, LDL cholesterol, triglycerides, AST and ALT were analyzed by enzymatic colorimetric method in Mindray BA-88A semi auto-analyzer (Mindray medical International LTD, China). HDL- cholesterol was determined by precipitation method and bilirubin was quantified by spectrophotometric method by Mindray BA-88A semi auto-analyzer (Mindray medical International LTD, China). Serum creatinine was measured by kinetic method, whereas PT/INR and FBC was done by the manual method.
Parametric and non parametric statistical tests will be applied using the SPSS version 14 (SPSS Inc., Chicago, IL, USA) and Stata/SE 10.0 (Stata Corporation, College Station, TX, USA) for the data analysis. The total number of subjects recruited for the study was 30, out of which 28 completed the three months follow up (Fig. The mean age (±SD) of the subjects was 38.8 ± 10.4 years (range 21–58 years), and there was a 1:1 gender distribution. Mean (±SD) BMI, waist circumference, hip circumference were 24.8 ± 3.6 kgm −2, 86.6 ± 10.6 cm and 97.8 ± 9.0 cm respectively. The mean (±SD) total cholesterol, LDL cholesterol, HDL cholesterol, VLDL cholesterol and triglyceride were 226.4 ± 38.7 mg/dl, 152.8 ± 37.1 mg/dl, 52.7 ± 14.2 mg/dl, 24.6 ± 15.2 mg/dl and 112.1 ± 49.9 mg/dl respectively, while the mean fasting blood glucose level was 91.2 ± 6.9 mg/dl (range 80–104 mg/dl).
The mean systolic blood pressure, diastolic blood pressure, pulse rate, serum creatinine, AST, ALT, serum bilirubin and PT/INR were normal level at the baseline. Study population characteristics are summarized in Table.
CZ 85 mg, 250 mg and 500 mg capsules were supplemented over a period of three months, in monthly escalating doses. Clinical and biochemical assessments were done according to the schedule described in Table. There were no significant changes in the following anthropometric parameters during the three months follow up; weight, BMI, waist circumference and waist to hip ratio. There was a significant decrease in the hip circumference between baseline (Visit ‘0’) and the first visit (1 month), and also between baseline (Visit ‘0’) and the final visit (3 months) (Table ).
A significant increase in the pulse rate was noted between visits 2 (2 months) and 3(3 months) ( p. Mean ± SD P1. P2. P3. P4. Visit ‘0’ (Baseline) Screening Visit ‘1’ (1 month) CZ 85 mg Visit ‘2’ (2 months) CZ 250 mg Visit ‘3’ (3 months) CZ 500 mg Pulse rate (min −1) 73.4 ± 8.4 71.9 ± 9.2 71.5 ± 8.4 75.8 ± 8.6 NS NS.
The main objective of the study was to evaluate the medium-long term safety and pharmacodynamic properties of CZ. This study was conducted as a phase I clinical trial over a period of three months, with monthly escalating doses of CZ (CZ 85 mg, 250 mg and 500 mg) in healthy adults. In the present study CZ was given to healthy adults which shown to contain a lesser coumarin content , , compared to Cinnamomum cassia. Several biochemical and clinical parameters were assessed throughout the study to assess pharmacodynamic properties and toxicity. To assess the safety of supplementation of CZ, liver and kidney functioning tests were done at the baseline and at the end of each month.
Participants were screened initially and at the end of each month to see any undesirable effects occurred due to the CZ supplement. However there were no such effects other than the dyspeptic symptoms requiring discontinuation of treatment in 2 participants out of 30. A significant reduction in systolic/diastolic blood pressure, TC and LDL-c was noted at the end of the 3 months follow up period. The fact that CZ reduces arterial blood pressure has been concluded by several in-vivo animal studies. Nyadjeu et al. examined the effects of CZ extracts on mean arterial blood pressure (BP) of normotensive (NR) rats, salt-loaded hypertensive rats (SLHR), L-NAME (Nitro-L-Arginine Methly Ester) induced hype.