Effect of curcumin on fatigue and musculoskeletal health in postmenopausal women: a double-blind randomised controlled trial

Abstract

Objectives

Considering the proven anti-inflammatory effects of curcumin, we aimed to investigate the effect of curcumin supplementation on fatigue and musculoskeletal health (primary outcomes) and depression and its side effects (secondary outcomes) in postmenopausal women.

Design

This was a parallel-group, double-blind, randomised placebo-controlled superiority trial.

Setting

The trial was conducted at two general clinics in Tabriz, Iran, in 2023.

Participants

A total of 74 postmenopausal women were enrolled. The participants were women aged between 40 years and 60 years with normal menopause and at least 1 year after amenorrhoea.

Intervention

They were randomly assigned (1:1 allocation ratio) using a block randomisation method to receive either 500 mg curcumin capsules (intervention group, n=37) or identical placebo capsules (control group, n=37) twice daily for 8 weeks. Both participants and researchers were blinded to the group assignments.

Primary and secondary outcome measures

Data were collected using the questionnaires of demographic characteristics, short form of the perimenopausal fatigue scale, musculoskeletal health, Beck Depression Inventory (BDI-13) and the side effects checklist. Independent t, ANCOVA and Mann-Whitney U tests were used to compare the results between the two groups.

Results

A total of 74 women were randomised, with 33 in the curcumin group and 31 in the placebo group completing the study and being included in the final analysis. After the 8-week intervention, ANCOVA adjusting for baseline values revealed that the curcumin group showed a statistically significant improvement in musculoskeletal health (mean difference (MD): 5.3; 95% CI: 3.3 to 7.4; p<0.001); the observed mean difference falls just short of the MCID (the minimum clinically important difference), yet it is remarkably close. A statistically significant decrease in fatigue scale (MD: −2.6; 95% CI: −3.8 to −1.4; p<0.001) was observed compared with the placebo group; there is no MCID validated for this scale. No significant difference was observed between the groups in terms of depression (p=0.245); there is no universally accepted MCID specifically validated for the BDI-II 13-item version. Some participants reported side effects including stomach ache and headache, leading to dropout.

Conclusion

In this trial, an 8-week supplementation with curcumin was more effective than placebo at improving musculoskeletal health and reducing fatigue score in postmenopausal women. The study was not able to demonstrate a significant effect on depression.

Trial registration number

Iranian Registry of Clinical Trials (IRCT): IRCT20120718010324N72. Last updated version: 18 October 2022. Actual start of recruitment: 23 January 2023.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Rigorous double-blind, randomised, placebo-controlled design.

• A priori power calculation for the primary outcomes.

• Underpowered to detect a significant effect on the secondary outcome of depression.

• Short follow-up period and exclusive use of subjective outcome measures.

• Insufficient sample size for a definitive safety and side-effect analysis.

Introduction

Menopause is a significant stage in a woman’s life, defined by the WHO as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity.¹ This natural process is not a single event but a gradual transition that can profoundly impact a woman’s physical, mental and emotional well-being. The internationally accepted Stages of Reproductive Aging Workshop+10 criteria² provide a framework for this continuum, dividing it into distinct phases:

• The menopausal transition (or perimenopause): this phase begins with increasing variability in menstrual cycle length and ends with the final menstrual period. It is characterised by a decline in the production of sex hormones, primarily oestrogen, but also progesterone and testosterone.

• Postmenopause: this stage begins after the final menstrual period and is clinically diagnosed retrospectively after 12 consecutive months of amenorrhoea. Natural menopause typically occurs between the ages of 49 years and 52 years, with a global average age of approximately 50 years.

With increasing life expectancy, women may now spend one-third to one-half of their lives in the postmenopausal stage.³ Furthermore, the number of menopausal women worldwide is projected to reach 1.2 billion by 2030, making the associated health issues a growing global concern.⁴ The hormonal fluctuations and eventual cessation of oestrogen production during this transition can trigger a wide range of physical and psychological symptoms. Unpleasant physical symptoms include hot flashes, night sweats, genitourinary atrophy and muscle stiffness. Concurrently, women may experience emotional changes such as anxiety, depression and irritability.^{5 6}

Fatigue is one of the most common and distressing symptoms experienced by women during menopause. It is clinically important because it may be debilitating.⁷ Fatigue is characterised as a decrease in the ability to start or maintain activity or attention and is divided into two categories: central and peripheral. It has three dimensions, including the physical dimension (pain, musculoskeletal fatigue), the psychological-social dimension (limiting social activity due to fatigue or mood disorder) and the cognitive dimension (reduced ability to maintain attention and memory impairment).⁸ Fatigue can have various causes, such as drug use, iron deficiency anaemia, depression, anxiety disorders, job burnout and chronic fatigue syndrome. In addition, the inflammation caused by diseases can also lead to fatigue.⁹ There is growing and compelling evidence that oestrogen depletion during menopause can result in a systemic inflammatory state. This state is characterised by the production of systemic inflammatory cytokines derived from reproductive tissues, changes in the cellular immune profile, increased availability of inflammatory proteins in the CNS and a pro-inflammatory microenvironment that makes the brain vulnerable to ischaemic stress and other stressful factors. As a result, women going through menopause tend to experience more intense fatigue due to these changes.¹⁰

In a study conducted on 300 women in South America, it was found that 85.3% of postmenopausal women and 46.5% of perimenopausal women experienced physical and psychological symptoms of fatigue. However, only 19.7% of premenopausal women shared the same complaint.¹¹ A separate study in Japan revealed that 86% of middle-aged Japanese women who visited a menopause clinic felt tired more than once a week, and 49% felt tired almost every day.¹² Another study showed that 85% of middle-aged Japanese women and 82% of middle-aged Australian women experienced some level of fatigue.¹³

Muscle pain is a common symptom that women may experience during menopause. Due to the well-known role of oestrogen on musculoskeletal function, postmenopausal women experience a rapid decrease in muscle mass and strength. As a result of ageing, they are more vulnerable to weakness and bruising.¹⁴ According to a recent review, postmenopausal women are at higher risk of severe muscle pain compared with non-menopausal women. The prevalence of muscle pain and soreness in menopause is reported to be 50%.¹⁵

Curcumin is a powerful substance found in turmeric rhizome with the scientific name Curcuma longa.¹⁶ It has anti-inflammatory, antimicrobial and antioxidant properties.¹⁷ Numerous studies have demonstrated that curcumin can inhibit superoxide radicals,¹⁸ hydrogen peroxide and nitric oxide radicals contributing to oxidative stress.¹⁹ Curcumin has also been found to have a range of biological activities,²⁰ including antiobesity,²¹ anti-inflammatory,²² anticancer,²³ antiangiogenesis,²⁴ antidiabetes²⁵ and hepatoprotective effects.²⁶ In addition, curcumin can help with recovery and reduce fatigue.²⁷ Research has shown that its analgesic and anti-inflammatory properties may help reduce muscle damage, pain, fatigue and kinase activity after eccentric muscle activity.²⁸

Due to the decrease in oestrogen levels and the subsequent increase in inflammatory factors, postmenopausal women often experience a syndemic burden of unpleasant symptoms, including both fatigue and muscle pain.²⁹ Curcumin, with its well-documented anti-inflammatory and analgesic properties,³⁰ presents a plausible therapeutic candidate for addressing these complaints.

While previous research has demonstrated curcumin’s efficacy in improving musculoskeletal health in populations with osteoarthritis³¹ and in reducing exercise-induced muscle soreness,¹⁵ its effect on the chronic, non-exercise-related musculoskeletal complaints common in menopause remains largely unexplored. Likewise, studies on curcumin and fatigue have primarily focused on recovery from physical exertion in athletic populations,³² not on the persistent, systemic fatigue experienced during the menopausal transition.

Therefore, the novelty of this study lies in its targeted investigation of curcumin as a potential intervention for the concurrent burden of chronic fatigue and general musculoskeletal pain specifically within a postmenopausal population. Considering this gap, we aimed to investigate the effect of curcumin supplementation on fatigue and musculoskeletal health (primary outcomes) and depression and its side effects (secondary outcomes) in postmenopausal women.

Methods

Type of study and participants

This study was a double-blind randomised clinical trial in which the researcher and the participants were unaware of group assignment. It was conducted on 74 postmenopausal women referred to the Sheikh Al Rais Clinic and Psychiatry Clinic of Imam Reza in Tabriz City-Iran.

Eligible participants for this trial were women aged 40–60 years who were confirmed to be postmenopausal, having had at least 1 year of natural amenorrhea. The exclusion criteria were then carefully applied to ensure participant safety and to isolate the effects of the intervention by creating a homogenous study population free from key confounding variables. To this end, individuals with active psychiatric or systemic inflammatory disorders were excluded, as these conditions are independent causes of fatigue, pain and depression. Similarly, women who had experienced a significant stressful event within the past 3 months were not eligible, given that acute stress can profoundly impact all study outcomes. Furthermore, participants with uncontrolled thyroid disease were excluded, as this is a well-known cause of fatigue and mood changes. To prevent co-interventions from confounding the results, the study also excluded the current use of other herbal medicines, antidepressants or medications that could affect menopausal symptoms. A history of tobacco or alcohol abuse was also exclusionary due to their significant and independent effects on systemic inflammation. Finally, for essential safety reasons, women with a known history of allergic reactions to turmeric were not enrolled, and those using anticoagulant medications were excluded due to the potential for curcumin to increase bleeding risk through interaction with these drugs.

Sample size

The study’s sample size was determined using G-Power software (V.3.1). The calculation was informed by the validation study for the Perimenopausal Fatigue Scale (Chiu et al).³³ Although our study involved postmenopausal women, we used perimenopausal fatigue data as a close proxy due to shared symptoms. From the reference study, the mean (M₁) duration of fatigue was 6.9 with an SD of 3.5. We hypothesised that curcumin would produce a clinically meaningful improvement, aiming to detect a 35% reduction from this baseline (M₂=4.48, SD=3.5). With a two-sided alpha (α) of 0.05 and 80% power (1−β), the required sample size was 34 participants per group. A similar calculation was conducted for our other primary outcome, musculoskeletal health, based on data from a study by Hill et al.³⁴ This calculation yielded a smaller required sample size of 16 participants per group. To ensure the study was adequately powered for both primary outcomes, we adopted the larger, more conservative sample size derived from the fatigue variable calculation. Accounting for 10% attrition over 8 weeks, we increased the sample size to 37 per group, totalling 74 participants.

Sampling

After the project was approved, the Ethics Committee of Tabriz University of Medical Sciences granted the necessary permission. The researcher obtained the ethics code (IR.TBZMED.REC.1401.560) and registered the project in the Iranian Registry of Clinical Trials (IRCT) system to receive the clinical trial registration code (IRCT20120718010324N72). The sampling process began after obtaining written permission. Convenience sampling was used, where the researcher examined all postmenopausal women who visited the Sheikh Al Rais Clinic and Psychiatry Clinic of Imam Reza in Tabriz city to check if they met the inclusion and exclusion criteria; if they were eligible, they were given details about the study and invited to participate. Written informed consent was obtained from those who agreed to participate. The questionnaires for demographic characteristics, short form of the perimenopausal fatigue scale, Musculoskeletal Health Questionnaire (MSK-HQ) and Beck Depression Inventory (BDI-13) were completed through inperson interviews.

Randomisation

Participants were randomly assigned to either the curcumin or placebo group using a random block design with blocks of four and six with an allocation ratio of 1:1. Opaque medicine bottles were used to conceal the allocation, and participants were given the bottles based on their order of entry into the study. The follow-up was scheduled for 8 weeks after the intervention.

Intervention

Following the completion of baseline assessments and randomisation, each participant was provided with an opaque, sealed medicine bottle corresponding to their assigned group. Each bottle contained 112 oral tablets, sufficient for the entire 8-week study duration. The curcumin (trade name Curcuma; NOW) and placebo tablets were prepared to be identical in size, shape, colour and taste by the Dineh Pharmaceutical Company and were provided to the researcher for distribution.

Participants were given clear, standardised verbal and written instructions. The written documentation included:

A summary of the study purpose and timeline.

Clear instructions to take one tablet twice daily, after meals (specifically, after breakfast and after dinner). This timing was recommended to enhance absorption and minimise potential gastrointestinal discomfort.

Contact information for the lead researcher for any questions or in case of adverse events.

To promote adherence, participants were given a simple calendar-style log sheet to tick off each dose as it was taken. Furthermore, they were reminded of the importance of consistent supplementation via weekly follow-up phone calls. During these calls, the researcher also inquired about any potential side effects and answered any questions the participant might have. This multifaceted approach was designed to maximise adherence and ensure the integrity of the intervention protocol. The evaluation and follow-up were conducted in two stages. The initial evaluation was conducted before the participants entered the study, and the second evaluation was carried out 8 weeks later.

Data collection tools

Data were collected using the questionnaires of demographic characteristics, short form of the perimenopausal fatigue scale, MSK-HQ, BDI-13 and the side effects checklist. The scales are available as online supplemental file 1.

Demographic characteristics questionnaire

This questionnaire included items such as age, duration of menopause, education, job, income, weight, height and level of satisfaction. Content and face validity were used to establish the accuracy of this questionnaire.

Short form of the perimenopausal fatigue scale

This scale was developed in 2021 by Chiu et al in Taiwan. This 13-item questionnaire was designed to assess the vulnerability of women in the premenopausal phase to fatigue syndrome. It includes four subscales: less efficiency, down-heartedness, living with body discomforts and unmet sleeping needs but difficulty in sleeping. For the purpose of our study, which focused on the severity of fatigue, a four-point Likert scale was used to evaluate the ‘disturbance level’ of each of the 13 symptoms, with scores ranging 0–3, where 0 indicates no fatigue, 1 indicates mild fatigue (a slight discomfort without affecting daily life), 2 indicates moderate fatigue (some discomfort with a mild impact on daily life, approximately 3 days per week) and 3 indicates severe fatigue (very distressing, significantly interfering with daily life, occurring daily). For the analysis in this study, the scores from all 13 items were summed to generate a single total fatigue score (range: 0–39), with higher scores indicating greater fatigue severity. This total score was used as the outcome variable in all statistical tests for fatigue score.³³ For the first time, psychometric analysis of this tool was done by our research team; the results showed a content validity index of 0.95, content validity ratio of 0.98 and Cronbach’s alpha coefficient of 0.75.

Musculoskeletal health questionnaire

This 14-item questionnaire assesses various aspects of musculoskeletal health: pain severity, physical function, activity level, pain interference, sleep difficulty, emotional well-being, diagnosis and treatment understanding, pain self-management and overall impact of symptoms. Respondents rate their condition over the previous 2 weeks on a five-point Likert scale. The total score ranges from 0 to 56. A higher score indicates better musculoskeletal health status.³⁵ A change of 5.5 points is considered the minimum clinically important difference (MCID) for this instrument.³⁶ For the first time, psychometric analysis of this tool was done by our research team; the results showed a content validity index of 0.94, content validity ratio of 0.96 and Cronbach’s alpha coefficient of 0.90.

Beck Depression Inventory

This scale was first designed by Beck in 1961; the short form has 13 items that measure general, behavioural and cognitive symptoms of depression. Each item has four options scored from 0 to 3, determining degrees of depression from mild to severe. The total score, ranging from 0 to 39, is interpreted by established clinical cut-offs where a higher score reflects more severe depression. A score of 0–4 indicates non-depressed, 5–7 mild depression, 8–15 moderate depression and 16–39 major depression.³⁷ A reduction of 17.5% from the baseline score is considered a clinically meaningful improvement.³⁸ In Lee’s 2017 study, the questionnaire had a Cronbach’s alpha of 0.89.³⁹ Rajabi also confirmed the validity and reliability of this questionnaire in Iran.⁴⁰

Data analysis

The data were analysed using SPSS V.26.0 software. No transformations were applied to the data. Baseline demographic and clinical characteristics of the participants in both the curcumin and placebo groups were summarised using descriptive statistics: means and SD for continuous variables and frequencies and percentages for categorical variables. The primary analysis to evaluate the effect of the intervention on the primary outcomes of fatigue and musculoskeletal health was conducted using analysis of covariance (ANCOVA). For this model, the postintervention score was the dependent variable, group allocation (curcumin vs placebo) was the independent factor and the respective baseline score of the outcome was included as a covariate. The Mann-Whitney U-test was used to compare the depression scores between groups, as these data did not follow a normal distribution. A significance level of p value <0.05 was considered for all tests. All analyses were conducted following the intention-to-treat principle.

Results

The sampling started in March 2023 and continued until January 2024. Out of the 87 people examined by the researcher, 74 individuals met the necessary criteria to enter the study. Three people were excluded from the study due to unwillingness, five people due to systemic disorders and five people due to thyroid disease. Among the 37 women assigned to each group, 33 individuals in the curcumin group and 31 in the placebo group completed the treatment period (figure 1).

Figure 1. Flow chart of the study.

The demographic characteristics of the participants are detailed in table 1, and no significant differences were observed between the study groups in this regard (p<0.05).

Table 1. Sociodemographic characteristics of the participants (n=74).

Characteristic	Curcumin (n=48)	Placebo (n=48)
	Mean (SD)	Mean (SD)
Age (year)	55.4 (3.1)	55.0 (3.2)
Menopause age (year)	50.4 (3.3)	48.9 (3.9)
Menopause time (year)	4.9 (3.4)	5.9 (4.5)
Body mass index (BMI)	28.2 (4.0)	27.9 (4.4)
	Number (per cent)	Number (per cent)
Marital status
Single	1 (2.7)	3 (8.1)
Married	31 (83.8)	26 (70.3)
Missed husband	3 (8.1)	7 (18.9)
Divorced	2 (5.4)	1 (2.7)
Job
Housewife	30 (81.1)	28 (75.7)
Working at home	1 (2.7)	5 (13.5)
Employed	6 (16.2)	4 (10.8)
Education
Illiterate	4 (10.8)	5 (13.5)
Primary	13 (35.1)	13 (35.1)
Secondary	8 (21.6)	10 (27.0)
High school	0 (0.0)	3 (8.1)
Diploma	5 (13.5)	2 (5.4)
University	7 (18.9)	4 (10.8)
Husband job
Unemployed	1 (3.2)	0 (0.0)
Worker	6 (19.4)	3 (11.5)
Shopkeeper	7 (22.6)	5 (19.2)
Other	11 (35.5)	10 (38.5)
Professional	1 (3.2)	1 (3.8)
Retired	5 (16.1)	7 (26.9)
Income sufficiency
Completely sufficient	5 (13.5)	6 (16.2)
Somewhat sufficient	27 (73.0)	26 (70.3)
Insufficient	5 (13.5)	5 (13.5)
Life satisfaction
Completely satisfied	13 (35.1)	7 (18.9)
Somewhat satisfied	19 (51.4)	23 (62.2)
Not satisfied	5 (13.5)	7 (18.9)
Physical routine
Yes	13 (35.1)	16 (43.2)
No	24 (64.9)	21 (56.8)
Hormone Replacement Therapy (HRT) history
Yes	2 (5.4)	3 (8.1)
No	35 (94.6)	34 (91.9)
Muscle pain
Yes	37 (100.0)	36 (97.3)
No	0 (0.0)	1 (2.7)
Physiotherapy history
Yes	6 (16.2)	8 (21.6)
No	31 (83.8)	29 (78.4)
Painkiller consumption
Yes	24 (64.9)	18 (48.6)
No	13 (35.1)	19 (51.4)
Pain intensity
None	1 (2.7)	1 (2.7)
Mild	10 (27.0)	12 (32.4)
Moderate	17 (45.9)	14 (37.8)
Severe	9 (24.3)	10 (27.0)
Sleep disturbance
Yes	19 (51.4)	17 (45.9)
No	18 (48.6)	20 (54.1)

The mean (SD) of the musculoskeletal health score before the intervention in the curcumin group was 29.8 (7.0), which increased to 38.1 (7.8) after the intervention; in the placebo group, it was 32.1 (9.3) before the intervention and 34.5 (9.9) after the intervention. According to the independent t-test, there was no significant difference between the study groups before the intervention (p=0.236). After the intervention, based on the ANCOVA test by adjusting the baseline score, the average score of musculoskeletal health in the curcumin group was significantly higher than the placebo group (MD: 5.3; 95% CI: 3.3 to 7.4; p<0.001). The established MCID for the MSK-HQ is 5.5 points.³⁶ Our observed mean difference falls just short of this threshold.

The mean (SD) of the fatigue score before the intervention in the curcumin group was 21.0 (4.2), which decreased to 16.7 (3.5) after the intervention; in the placebo group, it was 20.9 (4.7) before the intervention and 19.6 (4.8) after the intervention. According to the independent t-test, there was no significant difference between the study groups before the intervention (p=0.918). After the intervention, based on the ANCOVA test by adjusting the baseline score, the average score of fatigue in the curcumin group was significantly lower than the placebo group (MD: −2.6; 95% CI: −3.8 to −1.4; p<0.001) (table 2). There is no MCID validated for this scale.

Table 2. Comparison of the mean score of musculoskeletal health and fatigue among study groups.

Variable	N	Curcumin Mean (SD)	N	Placebo Mean (SD)	Mean difference (95% CI)	P value
Musculoskeletal health (Score range: 0–56)
Before intervention	37	29.8 (7.0)	37	32.1 (9.3)	−2.2 (−6.1 to 1.5)	0.236
After intervention	33	38.1 (7.8)	31	34.5 (9.9)	5.3 (3.3 to 7.4)	<0.001
Severity of fatigue (Score range: 0–39)
Before intervention	37	21.0 (4.2)	37	20.9 (4.7)	0.1 (−1.9 to 2.2)	0.918
After intervention	33	16.7 (3.5)	31	19.6 (4.8)	−2.6 (−3.8 to −1.4)	<0.001

The independent t-test was used before the intervention and ANCOVA after the intervention by adjusting baseline values to compare fatigue and musculoskeletal health.

ANCOVA, analysis of covariance.

The median (25th–75th percentile) score of depression was 6.0 (1.5–10.0) before the intervention and 3.0 (1.0–6.0) after the intervention in the curcumin group. It was 6.0 (2.0–9.0) before the intervention and 4.0 (2.0–8.0) after the intervention in the placebo group. According to the Mann-Whitney U test, there was no significant difference between the study groups before (p=0.807) and after the intervention (p=0.245) (table 3). There is no universally accepted MCID specifically validated for the BDI-II 13-item version; some consider a reduction of 17.5% in scores from baseline.³⁸

Table 3. Comparison of the mean score of depression among study groups.

Variable	N	Curcumin (n=37)		N	Placebo (n=37)		P value*
		Mean (SD)	Median (Percentile 25–75)		Mean (SD)	Median (Percentile 25–75)
Depression (score range: 0–39)
Before intervention	37	5.9 (4.3)	6.0 (1.5–10.0)	37	6.2 (6.0)	6.0 (2.0–9.0)	0.807
After intervention	33	3.7 (3.3)	3.0 (1.0–6.0)	31	5.0 (4.0)	4.0 (2.0–8.0)	0.245

^*Mann-Whitney U test.

After starting the treatment, two people in the curcumin group dropped out due to stomach pain, one due to headache and one due to allergy. In the placebo group, three people left the study because they did not want to continue, one due to lethargy and two due to stomach pain. Finally, 33 people in the curcumin group and 31 in the placebo group completed the process.

Discussion

The intervention with curcumin led to a statistically significant improvement in musculoskeletal health and reduced fatigue score in postmenopausal women. Although there was a decrease in the depression score, the difference was not significant.

Our results showed that curcumin supplementation led to a statistically significant improvement in the MSK-HQ score, with a mean difference of 5.3 (95% CI: 3.3 to 7.4) compared with placebo. The established MCID for the MSK-HQ is 5.5 points.³⁶ Our observed mean difference falls just short of this threshold, yet it is remarkably close. While previous research has largely focused on curcumin’s efficacy in specific pathologies like osteoarthritis,³¹ our findings broaden its relevance to the generalised, chronic musculoskeletal pain and stiffness frequently reported by postmenopausal women. This clinical effect is likely underpinned by a confluence of biological mechanisms, primarily curcumin’s potent anti-inflammatory activity via inhibition of the NF-κB signalling pathway and its capacity to mitigate systemic oxidative stress.⁴¹ Future research in this area could be significantly enhanced by incorporating objective biomarkers, such as quantitative sensory testing, which has shown promise in predicting treatment outcomes for musculoskeletal pain and could help elucidate the specific nociplastic or anti-inflammatory pathways modulated by curcumin.⁴² Moreover, our findings should be considered within the broader context of effective non-pharmacological interventions; the benefits of curcumin can be seen as complementary to established strategies like targeted muscle strengthening exercises, which are also proven to be highly effective in this demographic.⁴³

In this study, oral treatment with curcumin capsules led to a statistically significant reduction in fatigue score. However, there is no MCID validated for this scale. The antifatigue effect of curcumin likely extends beyond simple anti-inflammatory action; emerging evidence strongly suggests that curcumin enhances mitochondrial biogenesis and protects against mitochondrial dysfunction, thereby boosting cellular energy production and directly combating peripheral and central fatigue.⁴⁴ This is a critical consideration in an ageing population, as persistent fatigue is not merely a transient symptom but can be a key component of the trajectory towards functional decline and frailty. Understanding interventions that can mitigate fatigue may therefore have long-term implications for maintaining independence and vitality in later life.⁴⁵ The chronic symptom burden in our study is also a reminder of the complex interplay of factors that modulate patient experience, where even bioclimatic and environmental variables can influence the perception of musculoskeletal pain and fatigue.⁴⁶

In this study, oral treatment with curcumin capsules reduced depression; however, the effect was not significant statistically. There is no universally accepted MCID specifically validated for the BDI-II 13-item version; some consider a reduction of 17.5% in scores from baseline.³⁸ The neurobiological mechanisms underlying depression are complex and the therapeutic response is often gradual. Curcumin is hypothesised to exert its antidepressant effects through mechanisms such as modulating monoamine neurotransmitters (eg, serotonin), reducing neuroinflammation and promoting neurogenesis via pathways like Brain-Derived Neurotrophic Factor.⁴⁷ These processes of neuroplasticity and systemic change inherently take longer to manifest as measurable clinical improvements compared with more direct anti-inflammatory effects on muscle and joint pain.⁴⁸ Standard clinical trials for conventional antidepressants (eg, selective serotonin reuptake inhibitors (SSRIs)) typically use a duration of 8–12 weeks,⁴⁹ as it is understood that the full therapeutic effect may not be evident before this point. Therefore, a more suitable duration to robustly test curcumin’s effect on depression would likely be at least 12 weeks. The selection of an 8-week duration for the present trial was a pragmatic decision driven by our primary outcomes: fatigue and musculoskeletal health. The primary hypothesis was that curcumin’s potent anti-inflammatory properties would alleviate these symptoms. Based on existing literature, the anti-inflammatory and analgesic effects of curcumin are typically observed within a timeframe of 4–8 weeks.⁵⁰ Our study was therefore powered and timed specifically to detect a change in these primary endpoints. Depression was included as a key secondary, but more exploratory, outcome. We acknowledge that this duration, while appropriate for the primary outcomes, was likely suboptimal for definitively assessing the secondary outcome of depression.^{44 45} This highlights a critical limitation and underscores the need for longer-term trials (≥12 weeks) specifically designed to assess mood-related outcomes.^{48 49}

The insights from this study contribute to a wider understanding of symptom management in female-specific and female-predominant conditions. The positive response to an intervention targeting chronic pain and fatigue resonates with findings in related fields, such as fibromyalgia research, where both structured exercise programmes⁵¹ and targeted manual therapies⁵² are essential components of a multimodal management strategy. Our focus on a postmenopausal population is methodologically justified, as sex-specific analyses are critical for understanding musculoskeletal health and tailoring interventions appropriately.⁵³ Looking forward, the mechanisms of action for a systemic nutraceutical like curcumin may be even more complex than initially understood. There is a growing body of evidence supporting the role of the gut-microbiome-musculoskeletal axis in modulating pain and inflammation, providing a strong rationale for evaluating systemically acting anti-inflammatory compounds.⁴⁵ Future studies should explore this avenue, as curcumin’s effects on the gut microbiome could potentially explain its widespread benefits, linking it to the modulation of metabolites that influence joint health and pain perception.⁵⁴ While this trial demonstrates clear benefits, it is crucial to acknowledge that we did not employ a bioavailability-enhanced curcumin formulation, and future work using such preparations may yield even more pronounced clinical effects. In conclusion, our study strongly supports the role of curcumin in alleviating musculoskeletal pain and fatigue in postmenopausal women, paving the way for larger, longer-term investigations to confirm these findings and further explore its potential impact on mood and long-term functional outcomes.

Implication of findings

The study’s results indicate that curcumin may positively impact musculoskeletal health and reduce fatigue score in postmenopausal women. While these findings are promising and suggest that curcumin could serve as a complementary option for enhancing quality of life in this population, the reliance on subjective measures highlights a need for caution. To substantiate curcumin’s role as an effective intervention, future studies should incorporate physiological and biochemical measures, such as markers of inflammation, muscle strength and fatigue-related biomarkers. This approach would provide a more comprehensive understanding of curcumin’s effects, confirm its efficacy through objective data and enable more robust clinical recommendations. Expanding this evidence base could facilitate curcumin’s integration into complementary health strategies with greater confidence and precision.

Strengths and limitations

This study’s strengths include its rigorous double-blind, randomised, placebo-controlled design and an a priori power calculation for the primary outcomes. However, it is not without limitations. As noted, the trial was underpowered for the secondary outcome of depression, and the sample size was insufficient to make definitive conclusions regarding the intervention’s safety profile. The study did not employ a bioavailability-enhanced curcumin formulation (eg, with piperine), which may have limited the plasma concentrations achieved. Furthermore, we relied exclusively on subjective self-report measures and did not assess baseline dietary curcumin intake, which could introduce unmeasured variability.

Conclusion

The study results indicate curcumin’s positive effect on enhancing musculoskeletal health and reducing fatigue score among postmenopausal women. The substance was well tolerated by users, with only a limited number of reported side effects. To fully recommend curcumin as an effective and accessible treatment option in complementary medicine, it is necessary to carry out more clinical trials in this field. Future studies may also investigate the effect of curcumin on the health outcomes of non-menopausal individuals.

Data availability statement

Data are available upon reasonable request.