Effects of Curcumin Intake on CVD Risk Factors and Exercise-Induced Oxidative Stress in Healthy Volunteers—An Exploratory Study ^†

Abstract

Background: Evidence suggests that turmeric or curcumin intake can improve antioxidant defense, blood pressure, ageing and gut microbiota. The effects of turmeric concentrate (curcumin) intake on cardiovascular risk factors and exercise-induced oxidative stress were investigated. Methods: A randomized placebo-controlled study was performed to assess the effects of turmeric extract in healthy volunteers before and after a 30-minute exercise bout. Participants (n = 22) were given either 500 mg turmeric concentrate (Curcumin C3, Jarrow Formulas, Los Angeles, CA, USA) or placebo supplements. Anthropometry, systolic and diastolic blood pressure (SBP and DBP), pulse wave velocity (PWV), biomarkers of oxidative stress, perceived exertion and lipid peroxidation were assessed. Results: There were no significant differences in all baseline parameters between the placebo and the curcumin groups (p > 0.05). In the curcumin group, blood pressure response to exercise following curcumin intake was blunted, and the increase was not significant compared to basal values. In the last run, there was a significant difference (before–after) between curcumin and placebo groups (Δ in SBP: 7.3 ± 6.8 vs. 13.8 ± 6.3 mmHg, p = 0.007, and Δ in DBP: 2.3 ± 6.9 V 8.0 ± 6.8 mmHg, p = 0.012). Final PWV scores were reduced significantly in the curcumin group (7.2 ± 0.97 to 6.7 ± 0.77 m/s, p = 0.033), and this reduction was significant compared to the control (Δ of 0.56 vs. 0.21 m/s, p = 0.04). A significant increase was observed in urinary antioxidant power (p = 0.031) and total polyphenol levels (p = 0.022) post curcumin intervention, and those in the placebo did not show significant changes. The increase in exercise-induced MDA levels was blunted only in the curcumin group, and the before–after difference was significant compared to the control (Δ of −0.81 vs. +0.205 μmole/day, p = 0.032). The distance ran by the participants taking curcumin was significantly longer (p = 0.005), and compared to the placebo, the before–after difference was significant (Δ of −0.69 vs. +0.28 km, p = 0.014). Conclusion: Our study suggests that turmeric concentrate intake can reduce blood pressure and improve antioxidant, anti-inflammatory status and arterial compliance. Curcumin may improve exercise performance and ameliorate oxidative stress. Larger studies are warranted to validate these findings and test other cardiovascular risk factors.

1. Introduction

Regular physical exercise is known to convey several health benefits and is regarded to be a good practice to combat many metabolic diseases including cardiovascular disease (CVD), cancer, obesity, and diabetes [1,2,3]. However, strenuous, and prolonged exercise generates inflammatory cytokines and reactive oxygen species (ROS) [4,5]. It has been reported that the negative effects associated with eccentric exercise such as inflammation and DOMS are caused by a large increase in inflammatory cytokines in the working muscle, plasma and brain generated because of oxidative stress which stimulates the production of free radicals [5,6]. Retamoso et al. [7] found that eccentric exercise may cause delayed onset muscle soreness (DOMS), causing discomfort of skeletal muscles. MDA is the most used biomarker of oxidative stress in several conditions such as cancer, chronic obstructive pulmonary disease, and cardiovascular diseases [8]. It is vital to monitor both SBP and DBP throughout exercise. In addition, pulse wave velocity (PWV) is regarded the gold standard measurement of arterial stiffness and it is generally assessed by using carotid–femoral or brachial–ankle approaches [9]. PWV rises with stiffening of the aorta and consequently causes an earlier return of reflected pressure waves from the periphery to the aorta which enhances aortic SBP and reduces DBP [10]. In CVD and hypertensive patients, the incidence of oxidative stress can be determined in biological fluids by the thiobarbitoric acid (TBARS) assay [8,11]. These patients also display impaired antioxidant defense, and in the heart, the production of ROS exceeds the capacity of the antioxidant defense mechanism to buffering the ROS, resulting in cardiac dysfunction, ischemia-reperfusion injury, hypertrophy, cell death and heart failure [11].

Curcumin is a natural polyphenol derived from the rhizome of Curcuma longa [12,13] that has antioxidative, anti-inflammatory, cardiovascular, mental wellbeing and ageing protective effects and interacts with gut microbiota and several other actions [14,15,16]. Curcumin and turmeric extract have been shown to improve oxidative stress markers [17] by acting on cytokine/ROS-mediated inflammatory pathways to reduce the expression of NFkB/cyclooxygenase-2, enhancing antioxidant activity [18] and inhibiting the production of prostaglandin and NF-kB signaling [19]. In addition, curcumin may have musculo-protective effects against exercise-induced muscle damage (EIMD) by inhibiting free radical formation in injured skeletal muscles [18,20]. The aim of this short preliminary study was to investigate the effects of turmeric extract (rich in curcumin) intake on exercise-induced oxidative stress, blood pressure, PWV and lipid peroxidation in human volunteers.

2. Methods and Results

Study Design: We used a randomized placebo-controlled parallel study to investigate the efficacy of curcumin supplementation on exercise-induced oxidative stress and blood pressure over a period of 11 days (Figure 1). The study was granted ethical approval by the Ethics Committee of Queen Margaret University (QMU); code, 11010149-Honors/Curcumin/DNBS/QMU Ethical Committee.

Supplement: Each participant in both groups was supplied with eight capsules, either turmeric concentrate (curcumin C3 complex (500 mg; Jarrow Formulas, Los Angeles, CA, USA) or placebo capsules made by filling empty gelatin capsules with corn flour.

Anthropometry and Physiological Measurements: Measurements of Body Mass Index (BMI) were facilitated by recording the weight and height of each subject on day 1 of the study, allowing us to calculate their BMI using the equation: [BMI = weight (kg)/height (m)²]. Arterial compliance measured by pulse wave velocity (PWV) was performed between the carotid and femoral artery (PWVcf) by means of a validated Vicorder™ device (Skidmore Medical Limited, Bristol, UK). Blood pressure (BP) was measured, and the average of three SBP and DBP readings were calculated. A Borg rating of perceived exertion scale (1–10) was used to measure each subject’s level of exertion and intensity during each of the 30-minute runs [21].

Urinary Biomarkers assays: Urinary Polyphenols Levels, Urinary FRAP excretion and MDA concentration were measured.

3. Discussion

This short study has highlighted some of the beneficial effects of curcumin supplements in healthy volunteers. The present study confirms the antioxidant and anti-inflammatory properties of curcumin as evidenced in the significant increase in antioxidant concentrations (FRAP) and total polyphenol levels in the urine samples of the curcumin group [16,22] (

Table 1. Total polyphenol concentration of 24-h urine samples measured in GAE/day. Data presented as the mean ± SD. Significance of data was measured against the basal concentration of each group (p value ≤ 0.05).

	Intervention	Polyphenol Concentration (mg GAE/day)	p-Value
Basal	Placebo	293.3 ± 73.3	-
	Curcumin	276.3 ± 92.2	0.275
First Run (Pre-Intervention)	Placebo	304.8 ± 95.2	0.659
	Curcumin	282.7 ± 85.7	0.772
Last-Run (Post Intervention)	Placebo	318.4 ± 57.1	0.254
	Curcumin	405.9 ± 132.6	0.022

). Studies have confirmed that polyphenols possess antioxidant and free radical scavenging properties, which reduce low-density lipoprotein (LDL) oxidation [23]. We believe that the increase in antioxidant and polyphenol concentrations might have provided a protective mechanism against vascular dysfunction by neutralizing free radicals and reducing BP during exercise [24] (

Table 2. SBP and DBP readings recorded for all participants at basal, first run and last run before and after the exercise. It also shows the Δ change (mmHg) in SBP and DBP between pre-exercise and post exercise. Significance levels: * < 0.05; ** < 0.01; *** < 0.001; ^NS > 0.05.

Curcumin	SBP			DBP
	Pre Exer	Post Exer	Δ Change	Pre Exer	Post Exer	Δ Change
Basal	121.8 ± 12.0	-		75.5 ± 6.9	-
First run	124.3 ± 11.8	139.8 ± 14.5 ***	15.5 ± 9.6	74.5 ± 5.4	81.8 ± 6.0 **	7.3 ± 7.2
Last run	126.4 ± 13.5	133.7 ± 15.3 *	7.3 ± 7.0 *	76.3 ± 8.6	78.6 ± 7.2 NS	2.3 ± 6.9 *
Placebo	Pre Exer	Post Exer		Pre Exer	Post Exer
Basal	120.6 ± 12.2	-		73.9 ± 7.5	-
First run	123.6 ± 14.2	138.1 ± 12.5 ***	14.5 ± 6.1	73.4 ± 3.1	80.6 ± 5.1 ***	7.2 ± 4.8
Last run	123.5 ± 13.0	137.3 ± 11.6 **	13.8 ± 6.3 NS	70.1 ± 7.8	78.1 ± 6.2 *	8.0 ± 6.8 NS

and

Table 3. Mean of the antioxidant concentrations of urine samples obtained from the FRAP assay. Data presented as the mean ± SD. Significant difference was measured against the basal concentration of each group (p ≤ 0.05).

	Intervention	Antioxidant Concentration (mmol Fe+2/day)	p-Value
Basal	Placebo	3.04 ± 0.57	-
	Curcumin	2.81 ± 1.8	0.216
First Run (Pre-Intervention)	Placebo	3.05 ± 0.42	0.956
	Curcumin	3.12 ± 1.29	0.558
Last-Run (Post Intervention)	Placebo	3.43 ± 1.22	0.839
	Curcumin	3.75 ± 0.94	0.031

).

This supports the data of published studies that showed curcumin intake was able to reduce BP [25]. Other CVD parameters that may be of relevance: Arterial stiffness compliance as measured by PWV_cf was significantly reduced after curcumin intake, indicating its cardiovascular beneficial effects [26]. Turmeric extract intake attenuated the exercise-induced increase in lipid peroxidation (

Table 4. TBARS as a determinant of lipid peroxidation was assessed by the estimation of MDA levels (μmole/day). Data are presented as the mean ± SD. Significant differences were measured against the basal concentration of each group.

	Intervention	MDA Concentration (μmol/day)	p-Value
Basal	Placebo	2.263 ± 0.74	-
	Curcumin	2.249 ± 0.91	0.825
First Run (Pre-Intervention)	Placebo	3.422 ± 0.97	0.026
	Curcumin	3.472 ± 1.2	0.002
Last-Run (Post Intervention)	Placebo	3.627 ± 1.43	0.040
	Curcumin	2.662 ± 0.68	0.328

). In addition, the Borg score of perceived exertion was lowered, and thus the curcumin group felt they were able to run at a greater intensity during the last run compared to their first run [27] (

Table 5. Mean exercise and perceived exertion parameters of participants before and after the intervention. Data presented as the mean ± SD. Significant difference for the last run was measured against the first run (p ≤ 0.05).

Curcumin	First Run	Last Run	p-Value
Distance (km)	3.66 ± 0.81	3.97 ± 0.94	0.005
Speed (km/h)	7.32 ± 1.61	7.45 ± 1.99	0.227
Borg Scale	4.08 ± 1.38	3.51 ± 1.1	0.131
Placebo	First Run	Last Run	p-Value
Distance (km)	3.38 ± 0.84	3.66 ± 0.72	0.186
Speed (km/h)	6.85 ± 1.67	7.22 ± 1.44	0.219
Borg Scale	4.13 ± 1.69	4.06 ± 0.95	0.924

). The limitations in this present study were that of short duration with a low number of participants, and the study implemented a parallel design due to the notion that both crossover and parallel designs offer advantages and disadvantages (

Table 6. Baseline demographics of all participants in the curcumin and placebo groups. Data presented as the mean ± SD.

	Placebo (n = 10)	Curcumin (n = 12)	Significance p-Value
Age	21.8 ± 2.2	22.1 ± 1.7	0.729
BMI (kg/m2)	24.7 ± 3.8	25.8 ± 5.3	0.524
Caffeine intake (cups/day)	0.8 ± 1.1	1.2 ± 1.1	0.336
Baseline PWV (m/s)	7.49 ± 0.6	7.51 ± 0.9	0.564
Exercise (h/week)	2.6 ± 1.3	1.8 ± 1.6	0.452
SBP (mmHg)	120.7 ± 12.4	123.4 ± 15.2	0.871
DBP (mmHg)	73.9 ± 7.5	75.5 ± 6.9	0.682

). Finally, the influence of oral bioavailability of turmeric and curcumin should be considered in relation to gut microbiota of individuals [28].

4. Conclusions

Our study has demonstrated that curcumin possesses antioxidant and anti-inflammatory properties which have proven to lower blood pressure and improve CVD risk factors, exercise performance and ameliorate oxidative stress. Larger studies investigating the effects of turmeric extract or curcumin on oxidative stress, exercise performance and other cardiovascular parameters are warranted.