The myriad health issues triggered by hormonal changes in postmenopausal women have garnered increasing attention in recent years [1-3]. Among various nutraceuticals and phytoestrogens, curcumin—a bioactive compound derived from Curcuma longa—has emerged as a promising candidate due to its favorable safety profile, multi-targeted biological activities, and growing evidence supporting its antioxidant, anti-inflammatory, and metabolic benefits [4,5]. Despite longstanding concerns about its limited bioavailability, recent advancements in formulation technologies have improved its clinical applicability [6,7]. Building on this interest, our previous meta-analysis synthesized data from 14 randomized controlled trials to assess curcumin’s effects on blood pressure modulation, enhancement of antioxidant status, liver function protection, and the alleviation of vasomotor symptoms specifically in postmenopausal women—a population particularly vulnerable to cardiovascular, metabolic, and menopausal-related complications [8]. While significant improvements were observed in several indices, the effects on bone health and certain metabolic parameters did not reach statistical significance [8]. This commentary aims to further explore the potential mechanisms underlying curcumin’s action, discuss the limitations of our research, and propose future directions based on the original study data.

Blood pressure regulation and antioxidant improvement
Our analysis revealed that curcumin significantly reduced systolic blood pressure (SMD −0.51) and diastolic blood pressure (SMD −0.63), while also increasing total antioxidant capacity (TAC) and superoxide dismutase (SOD) levels. These findings support the notion that curcumin may alleviate vascular tension by enhancing endothelial function and bolstering the body’s antioxidant defense system. Previous studies suggest that curcumin may promote nitric oxide (NO) production and inhibit the NF-κB signaling pathway, thereby suppressing vascular inflammation and regulating blood pressure [9-11]. NO, as a crucial bioactive molecule, plays a beneficial role in cardiovascular health. Studies have shown that NO can improve endothelial function and lower blood pressure, thereby exerting protective effects on the cardiovascular system [12]. In addition, NO may also play an important role in the prevention and treatment of osteoporosis in postmenopausal women by modulating osteocyte function [13]. Conversely, increased activity of NFκB has been associated with the development of both osteoporosis and cardiovascular diseases. Specifically, during bone resorption, NFκB activation promotes osteoclast formation. Therefore, targeting NFκB signaling may offer a novel therapeutic strategy to improve bone health in postmenopausal women [14].

Significance of liver function improvement
The significant reduction in AST levels observed in our study suggests that curcumin may possess a unique advantage in hepatoprotection. This finding is of particular clinical relevance for postmenopausal women who are predisposed to liver dysfunction due to metabolic alterations. In certain contexts, AST may exhibit greater sensitivity than ALT, particularly in patients with mitochondrial dysfunction. For instance, a study by Che et al. reported that AST levels were significantly higher in patients with non-alcoholic fatty liver disease compared to healthy controls, and this elevation was closely associated with impaired mitochondrial function [15]. It is important to note, however, that elevated AST levels may also reflect damage to organs other than the liver. For example, in patients with cardiovascular disease, myocardial injury can also lead to an increased AST level [16]. However, the lack of significant changes in ALT and other related indicators indicates that curcumin’s hepatoprotective effects may be selective or require longer intervention durations to manifest fully.

Non-significant findings for bone health and metabolic parameters
Although curcumin did not produce statistically significant improvements in bone mineral density, bone turnover markers, or metabolic parameters (such as blood glucose and lipid profiles), this does not necessarily negate its potential benefits. Several factors may contribute to these findings: 1) There were considerable variations in curcumin dosage, formulation, and duration of administration across studies. 2) Bone health and metabolic regulation often require longer-term interventions and observations, which short-term RCTs may fail to capture [17,18]. 3) A single intervention might be insufficient to counteract the complex endocrine and metabolic dysregulation in postmenopausal women; combined therapies with other nutrients or medications could yield synergistic effects [19]. 4) Baseline bone mineral density variations among participants may have influenced responsiveness to curcumin interventions, as population with higher baseline BMD might have less capacity for measurable improvements. Furthermore, unaccounted differences in co-administered calcium and vitamin D intake between study cohorts could have modified curcumin’s biological effects, given the established role of these nutrients in bone metabolism.

Mechanistic insights
As a multi-target natural compound, curcumin’s anti-inflammatory and antioxidant properties have been well-documented [20-22]. By activating the Nrf2 pathway, curcumin upregulates the expression of various antioxidant enzymes, thereby reducing the generation of free radicals and reactive oxygen species (ROS) [23,24]. Concurrently, curcumin’s inhibition of the NF-κB signaling pathway leads to a decrease in the release of inflammatory cytokines, which improves endothelial function and reduces AST levels [24-26]. With regard to bone and energy metabolism, existing evidence suggests that curcumin may modulate calcium metabolism, inhibit bone resorption, and enhance insulin sensitivity [27]. However, these mechanisms require further validation and warrant additional investigation.

Clinical implications and future directions
The current data provide preliminary support for the use of curcumin in addressing certain health issues in postmenopausal women, particularly in terms of cardiovascular risk management and antioxidant protection. Nevertheless, several key considerations remain: 1) Heterogeneity in Samples and Dosages: The substantial variations in curcumin dosage, formulation, and treatment duration across studies have complicated data integration. To enhance comparability, future RCTs should utilize standardized doses and formulations to enhance comparability. Additionally, incorporating subgroup analyses based on baseline risk factors—such as obesity or hypertension—may help identify populations that are more likely to respond to curcumin interventions. 2) Long-Term Efficacy Evaluation: Improvements in bone health and metabolic parameters may necessitate longer observation periods. Future studies should extend follow-up durations and employ more sensitive indicators. 3) Exploration of Combined Interventions: Given the limited efficacy of single interventions, investigating curcumin in combination with other nutritional components, exercise, or pharmacological agents may offer a more comprehensive strategy for postmenopausal health management. 4) In-depth Mechanistic Studies: Employing molecular biology and metabolomics techniques to further elucidate the specific mechanisms of curcumin across different physiological systems will be crucial for optimizing clinical application strategies.

Overall, our meta-analysis provides empirical evidence supporting the beneficial effects of curcumin on certain health indicators in postmenopausal women, particularly regarding blood pressure regulation, enhanced antioxidant capacity, and improved liver function markers. However, the expected improvements in bone health and metabolic indices were not observed, highlighting the need for future research to focus on standardized samples, longer intervention periods, and more comprehensive mechanistic exploration. We anticipate that larger-scale, rigorously designed studies will yield a more robust scientific foundation for the application of curcumin in the management of postmenopausal women's health.

Dachuan Jin authored the manuscript, while Shunqin Jin contributed to the revision and finalization of the manuscript. All authors have approved the current version submitted for publication.

All authors declare that there are no conflicts of interest. The preparation and submission of this manuscript was not influenced by any commercial interests.

This study was supported by the 2024 Zhengzhou Municipal Science and Technology Innovation Guidance Program Project in the Medical and Health Field (Grant No.: 2024YLZDJH385) from the Zhengzhou Science and Technology Bureau.