Curcumin is the main component of the herb turmeric (Curcuma longa Linn.), member of the ginger family (Zingiberaceae), commonly consumed in Asian countries as spice and pigment. The bright yellow-orange color of turmeric comes mainly from fat-soluble, polyphenolic pigments known as curcuminoids. Curcumin, the principal curcuminoid, is a polyphenolic anti-oxidant compound that shown to have numerous molecular targets through which it exerts antioxidant, anti-inflammatory, anticancer, and neuroprotective functions[9]. Curcumin has been shown to be beneficial for a variety of diseases, including inflammatory diseases such as gastritis, pancreatitis, enterocolitis, nephritis and chronic bacterial prostatitis[11]. Curcumin was also found effective in suppressing in vitro prostate cancer tumour growth and metastasis[12].
Several studies investigated the efficacy and safety of curcumin in men with BPH. Most of these studies combined curcumin with other dietary supplements, including beta-sitosterol, phenols and oligomeric proanthocyanidins, or standard medications for BPH[10, 13, 14]. Furthermore, as these studies were conducted under ideal conditions, their results may not accurately reflect what happens in everyday practice. This observational study aimed to explore the efficacy of curcumin in treating moderate to severe LUTS secondary to BPH using real-world data.
The present study is the first to report clinical effects of a higher bioavailability formulation of Curcurmin complexed with gamma-cyclodextrins. The effects of curcumin naturally present in turmeric are largely hampered by its unfavourable pharmacokinetics, which include poor solubility, low gut absorption, and fast elimination[15]. Various formulations have been developed to improve pharmacokinetic profile and bioavailability of curcumin[11]; one of the most recent and promising formulation is CAVACURMIN®, a mix of curcuminoids (curcumin CAS 458-37-7, demethoxycurcumin CAS 22608-11-3, bisdemethoxycurcumin CAS 33171-05-0) and Gamma-cyclodextrin (CAVAMAX® W8 Food, CAS 17465-86-0). The addition of gamma-cyclodextrin ensures better dispersion of curcumin in water, improving intestinal absorption and bioavailability[16].
In this study, QURMIN® (CAVACURMIN®) proven highly effective for the treatment of patients with moderate-severe LUTS both alone and in combination with BPH-specific drugs. After 6 months of treatment with curcumin, storage symptoms improved in all subgroups, with a reduction in IPSS storage subscore of 3.9, 2.7, and 1.3 points for those receiving no additional treatment, AB therapy, and AB + 5-ARI therapy, respectively.
A large body of literature indicates that chronic inflammation is a key factor in the development and progression of BPH[17]. Patients with BPH and chronic prostatitis tend to suffer more severe LUTS with an increased risk of acute urinary retention due to glandular oedema[18]. These patients also present larger prostates and higher serum PSA levels[19]. Several studies demonstrated that curcumin can help suppress prostate inflammation by downregulating the expression of proinflammatory cytokines, including interleukin − 6 (IL-6), interleukin − 8 (IL-8), 5-lipoxygenase (5-LOX), and Tumor Necrosis Factor α (TNF-α)[20, 21]. In a rat model of BPH, curcumin was effective in suppressing the activation of the NF-kB pathway induced by testosterone, which is known to lead to an upregulation of IL-1β, IL-6, TNF-α, and COX-2[22, 23].
The results of this study are consistent with evidence from previous research. In a pilot study of 61 patients, the addition of curcumin to standard treatment for BPH improved symptoms such as urgency, frequency, and feeling of incomplete emptying[24]. In a study on 116 BPH patients, curcumin combined with tamsulosin and finasteride improved urinary retention symptoms and QoL compared to tamsulosin and finasteride alone[13]. A phase II clinical trial comparing curcumin and calendula officinalis against placebo showed that the former two substances were able to improve symptom burden, erectile function and Qmax in patients with chronic pelvic pain and chronic prostatitis[25].
Curcumin has been shown to inhibit the expression of Toll-like receptor 2 (TLR2) and TLR4 mRNA, thus reducing the release of inflammatory mediators in chronic urinary tract infections[26]. Curcumin, in combination with other compounds, has shown to improve the efficacy of prulifloxacin when used to treat chronic bacterial prostatitis[27]. Curcumin products reduced inflammatory symptoms even after TURP and TURB procedures and helped prevent late complications such as urethral stenosis and bladder neck sclerosis[14].
BPH is also prompted by the accumulation of mesenchymal-like cells derived from the prostate epithelium through the epithelial-mesenchymal transition (EMT) and immune-mediated cell proliferation[28]. Curcumin has been shown to downregulate the expression of vimentin and Toll-like receptor 4 (TLR4), thus suppressing cell proliferation and epithelial-mesenchymal transition mediated by the activation of transforming growth factor β1 (TGF-β1) signalling pathway[20]. Curcumin is also capable of inhibiting BPH and prostate cancer cell proliferation by enhancing androgen receptor (AR) degradation[29]. The stromal fibromuscular AR is known to be able to modulate signalling between epithelial and stromal cells, thus affecting the production of extracellular matrix and growth factors[30]. Targeting the stromal fibromuscular AR with curcumin leads to a reduction in prostate size[29].
In the current study, QURMIN® demonstrated to improve voiding symptoms in drug-naïve patients (-2 points in IPSS voiding subscore) and in patients taking ABs (-1.3 points). A reduction in voiding symptoms was also found for patients treated with AB + 5-ARI (-0.6 points), but the change was not significant compared to the control group. Similarly, Ledda et al. demonstrated significant improvement in stream weakness, straining and total IPSS score when curcumin was added to the best standard management (BSM) for 24 weeks[24]. Quiao et al. found that curcumin combined with tamsulosin and finasteride resulted in a 5-point reduction in the IPSS voiding subscore after 6 months, but this change was not statistically significant when compared to the control group[13].
We found that several uroflow parameters were positively affected by curcumin supplementation. In patients not assuming BPH-specific drugs, curcumin significantly increased Qmax (mean change + 3.1 ml/s), Qmean (+ 1.9 ml/s) and reduced PVR (-5.7 ml). Patients taking ABs showed a significant improvement only in Qmax (+ 1 ml/s) but not in Qmean and PVR. An overall improvement in uroflow parameters were reported for patients receiving AB + 5-ARI but none of those were significantly different than controls.
This study examined symptom burden and impact on QoL through the IPSS-QoL and BII items. The latter is particularly useful as it captures clinically relevant information on BPH-related symptoms and urinary difficulties, particularly those described as most vexing by patients[31]. Improvement in QoL was strictly related with the alleviation of storage symptoms, such as urinary frequency, urge incontinence and nocturia, which are the symptoms that have the greatest impact on work and social potential. Other studies demonstrated significant improvement in QoL after curcumin supplementation[13, 24].
In the present study, curcumin supplementation resulted in an overall improvement in patients' reported symptoms, as demonstrated by the improvement in total IPSS scores; after 6 months, the total IPSS was reduced by 5.9 points in the no-treatment subgroup, by 3.6 points in the AB subgroup, and by 1.6 points in the AB 5-ARI subgroup. In addition, a significant decrease in mean PSA was reported for drug-naïve and AB patients (-0.3 and − 0.2, respectively) but not for AB + 5-ARI patients.
Multiple regression for total IPSS showed that higher IPSS storage subscores and higher PSA were predictors of a greater reduction in total IPSS score; conversely larger prostate volumes and a coexisting treatment with AB + 5-ARI were independent variables for predicting a smaller decrease in total IPSS. These findings can be attributed to curcumin's strong anti-inflammatory properties, which are especially beneficial for patients with chronic prostatitis and higher PSA levels[13, 14, 29]. Patients with large prostate glands who are taking a combination of AB and 5-ARI may find that curcumin is not as effective for them. Similarly, it was found that patients taking curcumin who were also receiving AB or AB + 5-ARI had smaller improvements in Qmax.
It is worth noting that, even though curcumin demonstrated anti-proliferative properties, it did not significantly reduce prostate volume in any of the treatment groups; in other studies six months of curcumin supplementation resulted in a reduction of prostate volume that was not statistically significant[13]. It is probable that a larger effect on prostate volume might be achieved by continuing to supplement curcumin for a longer duration. In this respect, even 5-ARI have been shown to be clinically beneficial only when taken for extended periods (over six months)[32, 33]. In this respect, the difficulty in obtaining an accurate estimate of prostate volume by ultrasound is a potential contributing factor to the lack of significance in small differences between comparison groups.
In this study, QURMIN® was safe and well-tolerated by patients, with no specific drug reactions reported; the side effects observed in patients treated with AB or AB + 5ARI are typical of the baseline treatment and curcumin supplementation did not increase their incidence or magnitude.
This study is not devoid of limitations. First, the study was designed as a single-center study with a relatively small number of patients enrolled in each treatment arm. Second, the follow-up period of 6 months is relatively short, which may make it difficult to assess some outcomes, including prostate volume change, or to study the long-term persistence of therapeutic effect after curcumin is suspended. Ideally, a more comprehensive evaluation would include assessments at multiple time points throughout a longer follow-up. Third, this study was not designed to explore the effect of curcumin on erectile function. Erectile disfunction is frequently associated with BPH and curcumin already proved beneficial in protecting erectile function in these patients. However, erectile dysfunction is often linked with BPH, and some evidence suggests that curcumin may help protect erectile function in these patients.