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The Effects of Curcumin on Left Ventricular Function in Patients with Chronic Renal Failure


1 Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
2 Nephrology, Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
3 Research Center for Chemical Injuries, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
*Corresponding author: Maryam Moshkani Farahani, Atherosclerosis Research Center, Baqiyatallah University of Medical Sciences, Tehran, IR Iran, E-mail: moshkani_farahani@yahoo.com.
Archives of Cardiovascular Imaging. 4(1): e38087 , DOI: 10.5812/acvi.38087
Article Type: Research Article; Received: Mar 29, 2016; Revised: Apr 9, 2016; Accepted: May 14, 2016; epub: May 28, 2016; collection: Feb 2016

Abstract


Background: Curcumin, a yellow substance found in turmeric, has not only antioxidative features and beneficial effects in the treatment of cancer, liver, heart, and pulmonary diseases but also anti-inflammatory and anticoagulative effects. This chemical has cardioprotective effects too.

Objectives: In this study, we examined the effects of curcumin on left ventricular (LV) function in patients receiving dialysis for chronic renal failure.

Methods: This study is a double-blind, placebo-controlled trial conducted on 35 patients with chronic renal failure undergoing dialysis in the dialysis center of Baqiyatallah hospital. The patients were randomly divided into 2 groups: the curcumin group (n = 20) and the control group (n = 15). The curcumin group received curcumin capsules at a dose of 500 mg every 8 hours for 6 weeks (1500 mg/d) and the control group received a placebo for 6 weeks at the same dose. Echocardiography was done before the use of the drug and once after the 6th week. Also, the ejection fraction (EF), representing LV function and size, was measured in both groups.

Results: The mean age was 44.2 ± 13.4 years for the curcumin group and 45.4 ± 6.2 years for the placebo group. The study population comprised 22 male and 13 female patients. There were no significant differences regarding demographic variables such as age, sex, and body mass index between the 2 groups. In the curcumin group, LVEF based on the volume changed from 50.6% ± 7.1% to 51.5% ± 6.8% (P = 0.130). In the curcumin group, LVEF based on the diameter changed from 51.8% ± 3.8% to 52.4% ± 3.5% (P = 0.112). The changes in the mean EF before and after the intervention were not significant in each group. The EF, based on ventricular volume and diameter, was not significantly different between the 2 groups. In addition, the pulmonary artery pressure mean in both groups did not significantly change after the intervention (P > 0.05).

Conclusions: The administration of curcumin in patients undergoing dialysis had no positive effects on enhancing LVEF and LV function. Further research is required to shed sufficient light on this issue.

Keywords: Curcumin; Left Ventricular Ejection Fraction; End-Stage Renal Disease; Dialysis

1. Background


The complications and abnormalities of the left ventricle (LV) are some of the most common problems among dialysis patients (1). For instance, in more than 72% of dialysis patients with chronic renal failure, LV hypertrophy is diagnosed (2). Heart problems in dialysis patients may impose significant additional costs and increase the probability of hospitalization and as such constitute the most probable cause of death among such patients (3).


Curcumin is a natural and yellow-colored material extracted from Curcuma longa (turmeric) with hepatic metabolism and intestinal excretion (4). Curcumin has anti-inflammatory effects by reducing the expression of inflammatory factors (e.g., NF-kB), enzymes (e.g., cyclohexane oxygenase-2 and 5-lipoxygenase), and cytokines such as TNF, IL-1, and IL-6 (5). Different studies on rats have reported the heart-related positive effects of curcumin in terms of the prevention of cardiac hypertrophy, cardiac muscle repair, improvement of cardiac function and reperfusion post myocardial infarction and ischemia (6-13). In different human studies, the positive effects of curcumin aside from those vis-à-vis cardiac disease have been reported on colorectal neoplasia (14), ulcerative colitis (15), diabetes type (2, 16) and obesity (17). One study reported that highly absorptive curcumin was able to improve LV diastolic function in hypertensive patients (18).


Although the positive role of curcumin in improving heart function in laboratory models has been proven 6, there is a dearth of relevant data on human models.

2. Objectives


Given the obvious benefits of reducing cardiac complications in patients with chronic renal failure undergoing dialysis, we sought to assess the effects of curcumin on the cardiac function in human models.

3. Methods


The present study was designed as a randomized, controlled, single-center clinical trial. The study was done with a pilot design in 2 groups of curcumin (n = 20) and placebo (n = 15). The sampling was done by placing the selected patients in 2 groups alternately. In other words, the 1st patient was placed in the curcumin group, the 2nd patient in the control group, the 3rd patient in the curcumin group, and so forth. The studied patients were all patients with chronic renal failure under dialysis. The age range was between 30 and 60 years. The exclusion criteria comprised a diagnosis of cardiac diseases such as coronary artery disease (based on coronary angiography or other noninvasive diagnostic tests), moderate-to-severe valvular heart disease, pregnancy and lactation, and refusal to give informed consent. The curcumin group received curcumin for 6 weeks at a dose of 500 mg every 8 hours (1500 mg/d), and the control group received a placebo drug at the same dose for 6 weeks. Before the start of treatment with curcumin and exactly after the 6th week, the patients underwent echocardiography and the ejection fraction (EF) representing LV function and size was measured for the 2 groups in the echocardiography department by echocardiologists. The time of echocardiography was 1 to 2 hours before dialysis.


3.1. Statistical Analysis

The obtained data were entered into IBM SPSS Statistics for Windows, version 21 (IBM Inc., Armonk, NY). The determination of the normal distribution of the quantitative variables was done via the one-sample Kolmogorov-Smirnov test. Then, the descriptive statistics of frequency, frequency percentage, mean, and SD were determined. The quantitative variables were compared between the 2 groups using the independent t-test. The χ2 test or the Fisher exact test was employed to compare the qualitative variables between the 2 groups. The quantitative values were compared before and after angiography using the paired t-test. A P < 0.05 was considered statistically significant.

4. Results


The study population was comprised of 35 patients, divided into 2 groups of curcumin (n = 20) and placebo (n = 15). Ten patients were excluded due to their termination of cooperation, lack of data, or curcumin side effects.


The demographic data such as age, sex, and body mass index showed no significant differences between the 2 groups (Table 1). The levels of hemoglobin and parathyroid hormone exhibited insignificant differences between the 2 groups (Table 1). The duration of dialysis and the cause of renal failure had no significant differences between the 2 groups (Table 2).


Table 1.
Patients’ Characteristics

Table 2.
Dialysis Data

The mean volume of the LV at end diastole in the curcumin group and the placebo group was 96.05 ± 16.39 cc and 104.67 ± 27.09 cc, respectively. The mean volume of the LV after drug administration was 96.05 ± 16.39 cc in the curcumin group and 104.67 ± 27.09 cc in the placebo group. The mean volume of the LV before and after intervention had no significant difference between the 2 groups. In addition, no significant difference was observed between the 2 groups before and after treatment (Table 3). LV diameter at end diastole was 4.94 ± 0.317 cm in the curcumin group and 5.25 ± 0.82 cm in the placebo group. The mean values for the curcumin and the placebo groups were respectively 4.84 ± 0.793 and 5.19 ± 0.591 cm. The mean values before and after intervention had no significant differences between the 2 groups. In addition, no significant difference was observed in the comparison of each group before and after treatment (Table 3, Figure 1). The EF before drug administration was 50.65% ± 7.06% in the curcumin group and 47.6% ± 8.58% in the placebo group. After the administration of the drug, the EF was 51.55% ± 6.84% in the curcumin group and 48.07% ± 7.06% in the placebo group. The mean value had no difference between the 2 groups before and after intervention. In addition, no significant difference was observed between the 2 groups before and after the intervention (Tables 3 and 4, Figure 1).


Table 3.
Comparison of LVEDV and LVEDD Before and After Curcumin Administration

Table 4.
Comparison of LVEF (Diameter and Volume) Before and After Curcumin Administration

Figure 1.
Comparsion of LVEF (Volume) Before and After Curcumin

The comparison of average global longitudinal strain before and after intervention showed no significant difference between the 2 groups (P > 0.05), and nor there was there any significant difference in each group before and after intervention (Table 5).


Table 5.
Comparison of Mean GLS and PAP Before and After Curcumin Administration

Five patients in the curcumin group showed drug side effects. One of the patients had heartthrob, 2 of them had hypertension, 1 patient had shortness of breath, and the remaining patient had heartburn. These side effects gradually lessened as the treatment and administration of proton-pump inhibitors continued. In the control group, 4 patients had some drug effects. One of the patients had atypical chest pain, 1 had nausea, and the remaining 2 patients had heartburn. The side effects gradually decreased as the treatment continued and proton-pump inhibitors were administered. No dangerous or life-threatening events were observed in either of the groups (Figures 2 and 3).


Figure 2.
Comparsion of LVEF (Diameter) Before and After Curcumin

Figure 3.
Trial Flow Diagram

5. Discussion


The results of the present study indicated that curcumin had no significantly positive effects on increasing LVEF and decreasing LV volume. The comparison of the changes before and after treatment between the 2 groups and within each group showed no significant differences. The other echocardiographic indices associated with LV function did not present significant changes after the administration of curcumin inasmuch as average global longitudinal strain, representing the tissue velocity and myocardial function of the ventricle, did not indicate significant changes. In other words, the mean values obtained before and after treatment showed insignificant reduction in each group. Furthermore, curcumin had no positive effects on pulmonary artery pressure.


With respect to the side effects observed in the present study and the description of these conditions by the patients, it can be assumed that most of these effects may have been in consequence of gastrointestinal effects and gastroesophageal reflux (19-21). The fact that the side effects were observed in both groups and were similar suggests that curcumin had nothing to do with them and such effects were due to the side effects of other drugs.


Because the gastrointestinal absorption and bioavailability of curcumin are low, the reason for the ineffectiveness of curcumin in the present study may be its low dosage. In addition to the low dosage, the elimination of curcumin from the serums of the patients during dialysis might be another reason for this low serum level. Therefore, we suggest that further studies be conducted with higher doses of curcumin and usage of curcumin in a formulation which would offer better bioavailability. In addition, the effects of dialysis on the serum level of curcumin should also be probed into.


In light of the results of the present study indicating the ineffectiveness of curcumin in exerting positive effects on the LV, it seems advisable that studies with larger numbers of patients and more sub-group analyses be carried out with a view to arriving at more definite conclusions concerning the cardiovascular properties of curcumin in patients with chronic renal failure.

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Table 1.

Patients’ Characteristics

Curcumin (n = 20) Placebo (n = 15) P Value
Age, y 44.15 ± 13.35 45.33 ± 6.17 0.735
Male, No. (%) 12 (60) 10 (66.7) 0.482
BMI, kg/m 2 25.1 ± 6.54 25.64 ± 3.28 0.775
Hb, mg/dL 10.36 ± 1.08 10.13 ± 0.99 0.531
PTH, mg/dL 1911.09 ± 173.6 183.73 ± 167.4 0.901
Abbreviations: BMI, body mass index; Hb, hemoglobin; PTH, parathyroid hormone.

Table 2.

Dialysis Data

Curcumin (n = 20) Placebo (n = 15) P Value
Dialysis Duration, mo 15.05 ± 11.56 11.14 ± 5.27 0.247
Cause of Chronic Renal Failure Diabetes mellitus: 40% Diabetes mellitus: 40% 0.93
Hypertension: 50% Hypertension: 53.3%
Others: 10% Others: 6.6%

Table 3.

Comparison of LVEDV and LVEDD Before and After Curcumin Administration

Curcumin (n = 20) Placebo (n = 15) P Value
LVEDV before Curcumin Administration 97.1 ± 26.29 104.67 ± 27.09 0.412
LVEDV after Curcumin Administration 96.05 ± 16.39 102.93 ± 31.17 0.505
LVEDV within the Groups (P value) 0.137 0.302 -
LVEDD before Curcumin Administration 4.94 ± 0.317 5.25 ± 0.82 0.129
LVEDD after Curcumin Administration 4.84 ± 0.793 5.19 ± 0.591 0.157
LVEDD Within the Groups (P value 0.323 0.088 -
Abbreviations: LVEDD, Left ventricular end-diastolic diameter; LVEDV, left ventricular end-diastolic volume.

Table 4.

Comparison of LVEF (Diameter and Volume) Before and After Curcumin Administration

Curcumin (n = 20) Placebo (n = 15) P Value
LVEF (volume) before Curcumin Administration 50.65 ± 7.06 47.6 ± 8.58 0.257
LVEF (volume) after Curcumin Administration 51.55 ± 6.84 48.07 ± 7.06 0.097
LVEF (volume) within the Groups (P value) 0.130 0.719 -
LVEF (diameter) before Curcumin Administration 51.85 ± 3.84 50.67 ± 7.28 0.538
LVEF (diameter) after Curcumin Administration 52.95 ± 3.55 51.33 ± 6.04 0.064
LVEF (diameter) within the Groups (P value) 0.112 0.375 -
Abbreviation: LVEF, Left ventricular ejection fraction.

Table 5.

Comparison of Mean GLS and PAP Before and After Curcumin Administration

Curcumin (n = 20) Placebo (n = 15) P Value
GLS Average before Curcumin Administration -12.52 ± 2.87 -14.87 ± 2.86 0.099
GLS Average after Curcumin Administration -13.15 ± 2.98 -15.94 ± 1.74 0.081
GLS Average within the Groups (P value) 0.114 0.216 -
Mean PAP before Curcumin Administration 39.85 ± 18.87 38.13 ± 7.82 0.743
Mean PAP after Curcumin Administration 38.45 ± 17.57 36.8 ± 8.15 0.306
Mean PAP within the Groups (P value) 0.067 0.375 -
Abbreviation: GLS, Global longitudinal strain; PAP, Pulmonary artery pressure.

Figure 1.

Comparsion of LVEF (Volume) Before and After Curcumin

Figure 2.

Comparsion of LVEF (Diameter) Before and After Curcumin

Figure 3.

Trial Flow Diagram