Curcuminoids: Spicing Up Sympathovagal Tone

Turmeric rhizome, the yellow pigment found in curry, is commonly cultivated in India and China for medicinal purposes, as a food preservative, and as a textile dye [1]. Curcuminoids are a group of polyphenols comprised of three active analogs: curcumin, demethoxycurcumin, and bisdemethoxycurcumin [2], that are isolated from the rhizome portion of the turmeric plant (Curcuma longa). Curcumin, the most active and abundant component of turmeric, was first isolated about two centuries ago. Researched extensively over the past few decades, curcumin has a plethora of beneficial effects including antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activities [3, 4]. Various clinical trials using curcumin are underway, including treatment for pancreatic cancer, colon cancer, psoriasis and Alzheimier's disease [4].

More recently, curcumin has been reported to exert cardioprotective actions in animal models of hypertensive heart disease, myocardial infarction, cardiac hypertrophy and heart failure. These effects were attributed to curcumin's anti-oxidant and anti-inflammatory properties, as well as modulation of signal transduction cascades such as p38 and JNK, MAP kinases, NF-kB and p300 histone acetyltransferase-dependent transcriptional activation [5-8].

Curcumin also exerts beneficial effects in obesity- and diabetes-induced cardiovascular complications such as hyperlipidemia, hyperhomocysteinemia, insulin resistance, cardiac hypertrophy and atherosclerosis. In this issue of Nutrition, Pongchaidecha et al [9] determined whether curcuminoids prevent sympathovagal disturbance in obese mice fed a high-fat diet by reducing free fatty acids (FFAs). They report a new cardioprotective action of curcumin associated with FFA-induced sympathovagal disturbances, measured as a decrease in heart rate variability (HRV).

Clinically and experimentally, HRV is assessed by power analysis of heart rate interval spectra and is used as a measure of sympathovagal balance. Decreased HRV is an independent risk factor for cardiovascular disease, and is implicated in the pathogenesis of heart failure, atherosclerosis, hypertension and diabetic cardiac autonomic neuropathy [10].

The concept that FFAs modulate HRV is not novel [11]. However, the finding that administration of curcuminoids for 12 weeks in obese mice ameliorates hyperlipidemia, specifically FFAs, and improves cardiac autonomic function is novel and clinically relevant. Despite this promising effect, caution has to be used when translating these findings to patient care. Although curcumin consumption at doses as high as 12 g/day for 3 months were safe in Phase 1 clinical trials [12], its cardioprotective effects in humans remain to be determined. Recent clinical trials with antioxidant therapy in patients with cardiovascular disease have been disappointing, in part due to the timing of therapeutic intervention. Future studies are required to determine whether prophylactic use of curcumin as a dietary supplement will prevent or reduce HRV and cardiovascular events in obese, diabetic patients.

These studies raise several questions that warrant further investigation. Specific mechanisms by which curcumin lowers FFA levels, and how increased FFAs modulate HRV must be addressed. Results from such studies may identify new molecular mechanisms controlling HRV that serve as potential therapeutic targets. Nevertheless, the report by Pongchaidecha et al [9] provides further insight into the beneficial effect of curcuminoids on cardiovascular complications associated with obesity, and for the first time suggest that a dietary supplement could partially restore sympathovagal balance.