A randomized, placebo-controlled, crossover clinical trial to evaluate the effect of a turmeric formulation on muscle soreness and function recovery in moderately active adults

ABSTRACT

Background

Turmeric may alleviate exercise-induced muscle soreness (delayed onset muscle soreness) and muscular function loss due to the strong anti-inflammatory and antioxidant activities of its active compounds, the curcuminoids. The primary objective of this trial was to evaluate the effect of a highly bioavailable turmeric formulation on delayed onset muscle soreness in male adults.

Methods

In a randomized, double-blind, placebo-controlled, crossover trial (ClinicalTrials.gov NCT04946981), 44 moderately active adults (34 males, 10 females, mean [SD] age = 33.7 [6.4] years) ingested a turmeric formulation (300 mg/day, thereof 90 mg of active curcuminoids) or placebo for five days. On the second day, muscle damage was induced with exercise (30 min downhill run at 70% VO₂ max). Immediately before and 0, 24, 48, and 72 hours post-exercise, muscle soreness during squat on quadriceps (visual analog scale), muscular function (knee extension dynamometer), muscle power (vertical jump test), muscle damage (serum creatine kinase), range of motion (knee flexion), and perceived wellness and wellbeing (questionnaire) were assessed. During exercise, exhaustion was assessed using the Borg Rating of Perceived Exertion. The primary trial population consisted of the male participants, outcomes in females were considered exploratory. Adjusted least squares means with standard errors (SE) were obtained from mixed models for repeated measures.

Results

There were no significant differences between the turmeric formulation and placebo in muscle soreness area under the curve from pre-exercise to 72 hours post-exercise and at all timepoints, except for a trend observed in males 72 hours after exercise (adjusted mean [SE] for difference from placebo = −4.8 [2.7] mm, p = 0.0776). Muscle soreness recovery (difference between soreness at 72 hours and maximal post-exercise soreness) was significantly greater with the turmeric formulation compared to placebo (adjusted mean [SE] for difference from placebo = −10.7% [4.3%], p = 0.0184 for the male participants, and −7.9% [3.6%], p = 0.0346 for the total sample). Furthermore, in males, the decrease from pre-exercise to 24 hours after exercise in isokinetic peak torque was significantly lower with the turmeric formulation (adjusted mean [SE] for difference from placebo = 11.0 [4.9] Nm, p = 0.0275), as was the decrease in isokinetic max rep work (adjusted mean [SE] for difference from placebo = 11.6 [4.9] J, p = 0.0195), while vertical jump peak power at 24 hours after exercise was higher (median [interquartile range] with the turmeric formulation vs. placebo = 931.1 [825.9; 1001.1] W vs. 916.5 [824.8; 989.5] W, p = 0.0445).

Conclusions

Supplementation with the turmeric formulation can accelerate exercise-induced muscle soreness recovery and could attenuate muscular function loss and improve performance after unaccustomed exercise in young, moderately active, male adults.

1. Introduction

Unaccustomed high‑intensity eccentric exercise, such as downhill running or resistance training, can cause exercise-induced muscle damage (EIMD), leading to pain and discomfort known as delayed onset muscle soreness (DOMS) [1–5]. DOMS typically develops within the first 24 hours after exercise, peaks between 24 and 72 hours, and may persist for five to seven days [2,6,7]. It is often accompanied by stiffness of the affected muscles and temporary loss of muscular function and strength, limiting physical function for several days [8–10]. These symptoms may disrupt training, impair performance, and increase the risk of injury [11].

DOMS remains a relevant yet unsolved challenge in sports and exercise recovery. To reduce reliance on pharmacological interventions such as nonsteroidal anti-inflammatory drugs, research has examined a range of nutraceutical bioactives including polyphenols, catechins, and anthocyanins, as well as other nutritional compounds such as protein, caffeine, omega-3 fatty acids, and amino acids [11–15]. The rationale for these approaches stems from the multifactorial and still incompletely understood biology of DOMS, with key mechanisms thought to include mechanical muscle damage, the subsequent inflammatory response, involving activation of the cyclooxygenase pathway and neural sensitization [1,16,17]. Mechanical stress triggers the production of reactive oxygen species (ROS) and disrupts muscle structure, leading to immune cell infiltration, activation of the transcription factor nuclear factor-κB, and the release of cytokines and chemokines [1,17–19]. Structural damage and secondary muscle injury are also associated with reductions in muscular strength, function, and range of motion (ROM), along with elevated levels of creatine kinase (CK), lactate dehydrogenase, myoglobin, and, to a lesser extent, transaminases (alanine and aspartate aminotransferases) [17,19,20].

Given this context, the potent anti-inflammatory and antioxidant activities of turmeric (Curcuma longa), attributable to its active compounds, the curcuminoids, make it a promising candidate for modulating the mechanisms underlying EIMD [21]. Curcuminoids not only exert direct antioxidant effects that can reduce ROS levels but also activate the transcription factor Nrf2, which induces the expression of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase [22–24]. Through this dual mechanism, curcuminoids may help mitigate oxidative stress, inflammation, and associated EIMD and DOMS.

In interventional studies, common EIMD protocols include downhill running [25–27] and eccentric resistance exercise [28–35], as well as plyometric exercises (e.g. downhill jumping [36]) and high-volume protocols with novel movements (e.g. sit-stand repetitions [37]). These approaches typically target muscle groups such as the elbow flexors [29–31] and the major lower-extremity muscles [25–28,32–38]. Downhill running is a robust model for examining the physiological effects of eccentric muscle actions and EIMD, primarily by inducing eccentric contractions of the quadriceps, producing marked muscle damage and inflammation. It features in both road and off‑road running disciplines and can exacerbate EIMD, impairing performance [7]. Notably, three clinical studies assessing curcuminoid supplementation effects on DOMS applied downhill running protocols, which lasted 45 minutes at a 10–15% grade, at the anaerobic threshold [25], at 65% VO₂ max [26], and at maximal maintainable effort [27].

Several randomized, controlled clinical trials have found positive effects of curcuminoid supplementation on markers associated with EIMD and DOMS [25–39]. However, many of these [25,28,31,34,36,38,39] used dosages exceeding the FAO/WHO [40] and EFSA [41] acceptable daily intake (ADI) for curcumin (3 mg/kg body weight/day). Others used dosages close to the ADI, which could lead persons with a body weight under 50–60 kg to exceed it [27,29,30,32]. Two RCTs in young men investigated four to seven-day supplementation with 600 mg/day of a colloidal dispersion of turmeric extract (180 mg/day curcumin) administered either before or after muscle damage induced by eccentric elbow flexions. Pre‑exercise supplementation reduced inflammation (lower interleukin‑8), while post‑exercise attenuated DOMS and loss of ROM [29,30]. A single 1500 mg dose of a similar formulation (150 mg curcumin) taken by young men immediately after eccentric squat exercise reduced DOMS, CK, and transaminases, and increased total antioxidant capacity [32]. In healthy, moderately active adults, 500 mg/day of a bioavailable full spectrum turmeric formulation (250 mg/day curcuminoids) over four days following downhill running reduced DOMS, slightly lowered CK, and slightly increased VO₂ max [27]. The only short‑term (six-day), low‑dose study (400 mg/day of a solid lipid curcumin particle preparation, 80 mg/day curcumin) investigated leg press‑induced muscle damage in young adults, finding improvements in CK, tumor necrosis factor‑α, and interleukin‑8, with slight but non‑significant improvements in DOMS, interleukin‑6, and interleukin‑10 [33].

Other trials using dosages below the ADI involved longer‑term supplementation over several weeks [26,35,37]. Improved recovery with long-term administration due to reduced oxidative stress and inflammation may be accompanied by impaired longitudinal outcomes, such as reduced muscle mass gains and performance improvements. These typically accompany anti-inflammatory supplementation, such as with polyphenols, ω-3 fatty acids, and antioxidants [42]. This suggests that this practice may be beneficial in certain settings where longitudinal adaptations are not the primary concern, such as recovering between matches during the competition season but not in times when adaptations are paramount, such as during the competitive off-season. Therefore, formulations that are efficacious in a short-term setting, at doses below the ADI of curcumin [40,41], and supported by appropriate studies, are needed.

Turmeric extracts have a long history of use worldwide with a good safety profile [43]. However, a major limitation of these extracts is their extremely low oral bioavailability, caused by low absorption due to poor water solubility, rapid metabolism and rapid excretion following ingestion [44,45]. A dried colloidal suspension of curcuminoids has been shown to overcome this limitation with a high unconjugated and conjugated curcuminoid absorption in various supplement formats and food matrices [45,46]. Notably, a previous study demonstrated that a dose of 300 mg of this dried colloidal curcuminoid suspension achieved bioequivalence (AUC_24 h of total curcuminoids) to 1920 mg of standard turmeric extract [45]. Since no study to date has evaluated the effects of a short-term, low-dose, turmeric supplementation after downhill running, the aim of this study was to address this gap by testing the efficacy of this highly bioavailable dried colloidal suspension turmeric formulation (TF), at a low dose and short-term supplementation, for alleviating DOMS and muscular function recovery in moderately active adults after downhill running.

2. Materials and methods

2.1. Ethical conduct

This clinical trial was prospectively registered (21 June 2021) with ClinicalTrials.gov, identifier NCT04946981. Ethical approval was obtained from the appropriate local ethics committee (Clinical Research Ethics Committee of the Cork Teaching Hospitals, reference number ECM 4 (q) 12 January 2021 & ECM 3 (bb) 06/07/2021) and all participants gave written informed consent to participate in the research. The study was performed in accordance with the principles stated in the Declaration of Helsinki adopted by the 18^th World Medical Association General Assembly in 1964 and amended by the 64^th World Medical Association General Assembly in 2013.

2.2. Study population

Healthy, moderately active males and females, 25 to 45 years of age, and with a body mass index (BMI) of 18.5 to 28.0 kg/m², were eligible for inclusion. Moderately active referred to 15 to 20 km running and one to four hours of intentional physical exercise per week, including no more than one hour of lower body heavy-load or resistance training (to ensure sensitivity to the downhill running protocol). The BMI range was selected with the understanding that recreationally active individuals may have values slightly above the reference range, as BMI is not always an accurate measure of body composition or metabolic health, particularly for athletes or those with higher muscle mass [47]. Furthermore, eligible participants had to be willing to

• limit caffeine (400 mg/day), smoking (5 cigarettes/day), and alcohol consumption (1.5 and 2 drinks/day for females and males, respectively) during the entire study period, and abstain from alcohol 24 hours prior to EIMD.

• refrain from training for three days before the first test, five days before each EIMD, and during each supplementation period, including active recovery exercises.

• refrain from anti-inflammatory/pain reliever drugs during each supplementation period, from 24 hours pre- to 72 hours post-EIMD.

• refrain from recovery treatments over 72 hours post-EIMD, such as hydrotherapy, massage, stretching, compression garments, and topical applications.

Exclusion criteria included current musculoskeletal illnesses or conditions which could interfere with the study or pose significant risk to the participant, previous or current tumor or cancer diagnosis, sensitivity to herbal products or food allergies, surgery or significant injury in the lower limbs in the last six months, anticipated need for surgical or invasive procedure during the study, and significant abnormal laboratory results at screening. Participants were furthermore excluded if they consumed any dietary supplements four weeks prior to screening or during the study, followed any specific diet (e.g. high-protein, vegetarian, vegan), or had a history of drug or alcohol abuse. Participants taking any drugs such as antibiotics, laxatives, or immunosuppressants, anticoagulants or heparin, glucocorticoid or hyaluronic acid injections in the past three months, as well as with a history of noncompliance with medical treatments or recommendations were also excluded. In addition, participants required to perform squatting motions or descend a lot of stairs in their daily work activities or near or in the peak of training for an athletic race were excluded. Finally, pregnant or lactating females and participants currently involved in any other clinical trial or having participated in a trial within 90 days prior to randomization were excluded.

See ClinicalTrials.gov, identifier NCT04946981, for an exhaustive list of in- and exclusion criteria.

2.2.1. Sample size calculation

The sample size calculation was conducted by an independent statistician. The effect size to detect a difference between five-day supplementation with TF (300 mg/day) and placebo on DOMS in males was determined according to the literature [12,29,30]. The minimum relevant difference in the area under the curve (AUC) from pre-exercise to 72 hours post-exercise (AUC_72 h) for perceived muscle soreness was assumed to be 1.8 points (1.8 cm∙day = 18 mm∙day = 432 mm∙h) with a standard deviation (SD) of 2.95 points (708 mm∙h) for TF and 1.65 points (396 mm∙h) for placebo. A total of 29 evaluable male participants per treatment group was necessary to ensure an 80% power to detect a significant difference between TF and placebo for two-sided tests with an alpha level of 0.05 (corresponding to a type II error rate of 20% and a type I error rate of 5%). Assuming 15% of nonevaluable participants, up to a total of 35 male participants were to be randomized.

The available published data at the time of study design did not enable a power calculation for female participants. Consequently, 10 female participants were included to explore the outcomes in a female population without formal sample size calculation.

2.3. Study procedures

2.3.1. Study design

The study design was a randomized, double-blind, placebo-controlled, crossover clinical trial to evaluate the effect of TF or placebo on unaccustomed exercise-induced muscle soreness, muscle damage, muscular function recovery, wellness and wellbeing, and perceived exertion during exercise (Figure 1). During a five-day supplementation of TF or placebo, muscle damage was induced on the second day of supplementation with a 30-minutes downhill (grade −15%) run at 70% VO₂ max. This exercise protocol to induce muscle damage was derived from literature assessing the effect of an antioxidant-rich juice on EIMD following downhill running [14]. The supplement was ingested over five days (day −1, day 0, day 1, day 2, day 3; with day 0 being the day of the muscle damage-inducing exercise), in the morning before any food intake and two hours before the study visit. Apart from this supplement intake, participants attended the study visits fasted overnight for at least 10 hours. On the visits during the supplementation periods (V3-V10), participants received a standardized breakfast consisting of a package of cereal bars containing whole grain rolled oats (60%), sugar, vegetable oils (sunflower, rapeseed), honey, salt, molasses, emulsifier (lecithins), sodium bicarbonate (Oats & Honey Crunchy Granola Bars, Nature Valley; 42 g, 196 kcal, 7.6 g fat, thereof 0.9 g saturated, 27.0 g carbohydrates, thereof 11.3 g sugars, 3.6 g protein, 0.36 g salt) and 500 mL bottled water. Participants were given a list of unauthorized foods during the supplementation periods (red fruits, pomegranate, beetroot, watermelon, pineapple, red wine, curcuma, curry spices) and completed a 5-day food diary during the supplementation periods. After a washout period of 14 to 18 days, the TF and placebo groups were switched, and the described procedures were repeated.

Figure 1.

Study design.

2.3.2. Investigational and placebo products

The investigational product was a capsule supplement containing 300 mg TF, a dried colloidal suspension of curcuminoids made of standard turmeric extract, quillaja extract, sunflower oil, and acacia gum, containing a minimum of 30% curcuminoids (Turmipure Gold®, Givaudan France Naturals, Avignon, France) [45]. Specifically, one capsule contained 101.2 (2.2) mg curcuminoids, of which 86.6 (1.8) mg curcumin (mean and SD of a sample of 10 capsules). The placebo product was a capsule containing 300 mg of yellow/orange-dyed acacia gum, sterilized with gamma irradiation (maximum 3 kGy) and produced according to good manufacturing practices. The placebo capsules were inert, non-bioactive and indistinguishable from the TF capsules in appearance, taste, and texture.

2.3.3. Randomization and Blinding

Randomization was conducted separately for each sex using individual coding lists generated by an independent statistician, with a seed known only to that statistician, who was not involved in statistical analyses. These coding lists were sent directly to the manufacturing site which prepared and labeled the study products.The assignment of subjects to one of the two arms of this cross over study determined the supplementation order of TF and placebo and was carried out by randomization with individual coding. TF and placebo were provided in identical capsules to maintain blinding. This was a double-blind study, in which all research personnel and participants were blinded to the study products, except those involved in the production, labeling, and randomization. Unblinding occurred only after the study database was locked and the statistical analysis plan was finalized and signed by all parties.

2.3.4. Assessments

Detailed study procedures and assessments are listed in Table 1. To determine VO₂ max, participants performed a running test on a quasar® med treadmill (h/p/cosmos® sport & medical gmbh, Nussdorf-Traunstein, Germany) while secured with an overhead safety arch and harness to protect them from any risk of falling. The VO₂ max assessment began with participants running at a speed of 8–10 km/h at a 1% grade. This grade was maintained throughout the assessment, and running speed was increased by 1 km/h every minute, until participants reached their maximum running speed. The criteria for determining the cessation of the test and confirming the achievement of VO₂ max consisted of the following: (I) heart rate of 95% of the predicted maximum (220 minus years of age), (II) respiratory exchange ratio greater than 1.15, or (3) voluntary fatigue. Additionally, the VO₂ max value was sustained for 15 seconds before being recorded and used to determine the speed for the EIMD. Laboratory testing was conducted to measure CK, obtain a blood safety profile, and perform pregnancy testing. At Visit 1, a blood sample of 12 mL was collected for a safety profile (full blood count, chemistry, lipids, and glucose). Additionally, at Visits 3, 4, 5, 6, 7, 8, 9, and 10, a fasting sample of 4 mL was collected to measure CK levels. At Visits 3 and 7, 4 mL samples for CK measurement were collected twice – once before EIMD (fasted, before receiving breakfast) and once after EIMD (non-fasted). CK was measured by a laboratory accredited to the ISO 15189:2012 Medical Testing Standard using the CE certified Alinity c Creatine Kinase Reagent Kit (Abbott GmbH, Wiesbaden, Germany). For females of childbearing age, a urine sample was collected at Visits 1, 3, and 7 for pregnancy testing. Study outcomes were assessed pre-exercise and 0, 24, 48, and 72 hours post-exercise. Quadriceps muscular function of the dominant leg was assessed through isokinetic (90° ROM, 60°/s, 3 sets of 3 repetitions with 30 seconds rest between sets) and isometric (70° knee flexion, 3 repetitions of 5 seconds, with 30 seconds rest between each repetition) knee extensions on a Biodex™ System 3 Pro dynamometer (Biodex Medical Systems, Inc., New York, USA). In the vertical jump performance assessment, participants performed a countermovement jump on a jump mat (Chronojump Boscosystem®, Barcelona, Spain), using both legs, and with their hands on their hips, 3 sets of 3 repetitions with 30 seconds rest between sets. For the Biodex™ and jump performance assessments, the best performance was recorded. ROM was assessed using a standard goniometer during active knee flexion. The participants lay supine, raising the knee of their dominant leg, whilst keeping their foot on the floor. Perceived fatigue, sleep quality, general muscle soreness, stress, mood, and the sum of these (defined as overall wellness and wellbeing) were assessed with a psychometric test (Perceived Wellness and Wellbeing Questionnaire, Supplemental Figure 1) that is commonly used in training athletes [48–51].

Table 1.

Study procedures.

Study period	Screening		Supplementation period I					Washout	Supplementation period II
Study day	−14	−8	−1	0	1	2	3	14 to 18 days	n	n + 1	n + 2	n + 3	n + 4
Visit number	V1	V2	Phone call	V3	V4	V5	V6		Phone call	V7	V8	V9	V10
Timepoints relative to EIMDa				pre/0 h	24 h	48 h	72 h			pre/0 h	24 h	48 h	72 h
Procedures
Eligibility screen/review	x	x	x	xf	xf	xf	xf		x	xf	xf	xf	xf
Information and IC	x
Randomization		x
VO2 max		x
Physical assessment familiarization		x
Exercise for EIMDb				x						x
AE/SAE reporting		x	x	xf	xf	xf	xf		x	xf	xf	xf	xf
Screening & participant data
Demographics	x
Medical history	x
Prior/concomitant medications	x	x	x	xf	xf	xf	xf		x	xf	xf	xf	xf
Urine pregnancy test	x			xf						xf
Blood safety profile	x
Anthropometricsc	x			xf			xf			xf			xf
Vitalsd	x			xf	xf	xf	xf			xf	xf	xf	xf
Menstruation questionnaire				xf	xf	xf	xf			xf	xf	xf	xf
IPAQ-SF				xf						xf
5-day food diary			<———————–x———————–>						<———————–x———————–>
Outcomes assessment
Perceived exhaustion				0, 10 20, 30 min into exercise						0, 10 20, 30 min into exercise
Creatine kinase				pref/0 h	xf	xf	xf			pref/0 h	xf	xf	xf
Physical assessmentse				pre/0 h	x	x	x			pre/0 h	x	x	x
Wellness & wellbeing				pre/0 h	xf	xf	xf			pre/0 h	xf	xf	xf

AE, adverse event; EIMD, exercise-induced muscle damage; IC, informed consent; IPAQ-SF, International Physical Activity Questionnaire – Short Form; SAE, serious adverse event.

^apre refers to pre-EIMD, X h refers to X hours post-EIMD.

^b30 minutes downhill run at 70% VO₂ max.

^cHeight (only at V1), body weight, body mass index.

^dBlood pressure, heart rate, and temperature.

^ePerceived muscle soreness, Biodex assessments, vertical jump test, range of motion.

^fParticipants consumed a standardized breakfast on the visits during the supplementation periods (V3-V10). Procedures indicated with f were conducted fasted, procedures without f were conducted after breakfast.

2.4. Outcomes

The primary outcome was muscle soreness in the quadriceps after two squats reported on a visual analog scale (0–100 mm).

Secondary outcomes were:

• Muscle damage assessed by serum CK levels

• Muscular function recovery assessed by isokinetic peak torque, max rep work, and power (best out of 3 sets of 3 knee extension repetitions at 60°/s, 90° ROM), isometric peak torque (best out of 3 isometric knee extensions, 70° knee flexion, 3 × 5 seconds), countermovement jump height, velocity, and power (best out of 3 sets of 3 repetitions), and ROM

• Perceived wellness and wellbeing assessed with a psychometric test (Supplemental Figure 1) evaluating fatigue, sleep quality, general muscle soreness, stress, mood, and the sum of these (overall wellness and wellbeing)

• Perceived exertion assessed by the Borg Category-Ratio 0–10 Scale Rating of Perceived Exertion (RPE) [52] during the downhill run

Torque is a result of the combination of force and the distance from the axis of rotation. The peak torque represents the highest value of torque achieved during the entire ROM, serving as an indicator of maximal muscular strength. Work, on the other hand, is calculated by multiplying force and distance and represents the total amount of effort exerted throughout the entire ROM. It can be visualized as the AUC of force and distance. Max rep work refers to the maximum work performed in a single repetition, an indicator for muscular work output. This measure is considered a more reliable indicator of joint functionality compared to peak torque since it takes into account the muscle’s ability to maintain force throughout the entire ROM rather than just at one specific point. Power, which is calculated by dividing work by the time taken to perform the work, provides a true measure of the work rate intensity.

Except for RPE, endpoints for all outcomes were evaluated at each timepoint (pre-, and 0, 24, 48, and 72  hours post-exercise), change from pre-exercise to each post-exercise timepoint, and AUC_72h. AUC_72 h was calculated as the sum of the AUC at intermediate times ($\mathrm{AU}{\mathrm{C}}_{72\mathrm{h}}=\mathrm{AU}{\mathrm{C}}_{\mathrm{pre}-\mathrm{exercise}\mathrm{to}0\mathrm{h}\mathrm{post}-\mathrm{exercise}}+\mathrm{AU}{\mathrm{C}}_{0\mathrm{to}24\mathrm{h}\mathrm{post}-\mathrm{exercise}}+\mathrm{AU}{\mathrm{C}}_{24\mathrm{to}48\mathrm{h}\mathrm{post}-\mathrm{exercise}}+\mathrm{AU}{\mathrm{C}}_{48\mathrm{to}72\mathrm{h}\mathrm{post}-\mathrm{exercise}}$). Additional post-hoc endpoints for muscle soreness in males were maximum soreness within 72 hours after EIMD and percentage recovery of maximum soreness at 72 hours. Endpoints for RPE were change from 0 minutes at 10, 20, and 30 minutes into the downhill run at visit 3 and 7. Safety and tolerability were assessed through the follow-up of any treatment-emergent adverse events (TEAEs) and measurement of vital signs.

2.5. Statistical analyses

2.5.1. Statistical conventions

Statistical analyses were performed with SAS® Enterprise Guide software version 8.2 (SAS® for Windows version 9.4M6, SAS Institute Inc., North Carolina, USA). Statistical tests were conducted two-sided with a significance level of 5% (10% considered a trend), and 95% confidence intervals provided if applicable.

2.5.2. Descriptive statistics

Qualitative data and multinomial data were summarized with the number of participants with a non-missing value at each timepoint, and the number and percentage of participants for each modality. Missing values were not included in the denominator count when computing percentages. Quantitative data were summarized with the number of participants with a non-missing value at each timepoint, arithmetic mean, SD, median, first quartile, third quartile, minimum, and maximum. The descriptive statistics were unadjusted and reported in the supplemental material (Supplemental Tables 16–22).

2.5.3. Multivariate analyses

Multivariate analyses were conducted using mixed models for repeated measures (MMRM) including product group, sequence, sex for models on the totality of participants, supplementation period, timepoint on the supplementation period (not in AUC models), and product group × timepoint (not in AUC models) as fixed effects and participant nested sequence as random effect. The original analysis models defined in the statistical analysis plan, which were run on the full analysis and the per protocol sets, included pre-exercise values as a covariate to serve as baseline correction. However, since these values were collected 24 hours after initial product intake, they might have been influenced by product intake and could thus not be considered as true baselines. Therefore, sensibility analyses using models without the pre-exercise covariate were performed on the full analysis set based on the assumption that the true baseline for each period should be identical since the participants were their own control (crossover design). The results of these sensibility models without the pre-exercise covariate are reported in this publication. The models were fitted by estimated generalized least squares with restricted maximum likelihood estimates of covariance parameters and Kenward-Roger degrees of freedom approximation. Adjusted means of product effect (least square means), standard errors (SE), p-values and 95% confidence intervals were assessed within the framework of MMRM. The difference in adjusted means was used as effect size. If the carryover effect was significant (sequence effect; indicating the presence of carryover), the first period (free of carryover effects) only was analyzed and interpreted. If the carryover effect was not significant, the data from both periods was analyzed in the usual manner. The adequacy of the models was verified by residual analysis. Normality distribution of the residuals was verified by skewness and kurtosis (less than 1.5 in absolute value). If the adequacy of the MMRM could not be confirmed and carryover effect was not significant, median (interquartile range, IQR) was reported and product effect was analyzed with a non-parametric Wilcoxon Signed Rank test without adjustment of the variable. In this case, the effect size was the difference in medians.

2.5.4. Subgroup analyses

The primary analysis was in the male subgroup, and the secondary analysis in the totality of participants. At the time of designing the study, no studies have been carried out with this design on females. Therefore, as the analyses of this subgroup were underpowered, they were considered exploratory, and the results are reported in the supplemental material.

A post-hoc subgroup analysis on quadriceps soreness AUC_72 h was performed in participants with a soreness change from pre-exercise to any timepoint post-exercise ≥30 mm.

3. Results

3.1. Study participants

We included 34 (77.3%) male and 10 (22.7%) female participants in the trial. One additional male participant withdrew from the study after the randomization visit and before any product intake due to a conflict of schedule. The study flowchart is displayed in Supplemental Figure 2. Baseline characteristics are presented in Table 2.

Table 2.

Baseline characteristics.

	Males (n = 34)		Totality of participants (n = 44)
Males, n (%)	34 (100%)		34 (77.3%)
Age [years], mean (SD)	33.2 (6.3)		33.7 (6.4)
Education level, n (%) Higher certificate Honors Bachelor’s degree/professional qualification or both Ordinary Bachelor’s degree or national diploma Post-graduate diploma or degree Upper secondary	4 (11.8%) 16 (47.1%) 4 (11.8%) 8 (23.5%) 2 (5.9%)		4 (9.1%) 21 (47.7%) 6 (13.6%) 11 (25%) 2 (4.5%)
BMI [kg/m2], mean (SD)	Placebo: 24.58 (2.12)	TF: 24.63 (2.09)	Placebo: 24.36 (2.26)	TF: 24.40 (2.23)
Average caffeine consumption [mg/day], mean (SD)	143.9 (112.4)		132.8 (110.0)
Alcohol consumption, n (%) Consumes alcohol Does not consume alcohol For alcohol consumers, number of standard drinks/day, mean (SD)	27 (79.4%) 7 (20.6%) 0.95 (0.50)		33 (75.0%) 11 (25.0%) 0.84 (0.51)
Smoking status, n (%) Current smoker Non-smoker Past smoker	1 (2.9%), 5 cigarettes/day 30 (88.2%) 3 (8.8%)		1 (2.3%), 5 cigarettes/day 40 (90.9%) 3 (6.8%)
Physical activity, mean (SD) Vigorous MET [min/week] Moderate MET [min/week] Walking MET [min/week] Total physical activity MET [min/week]	Placebo: 475 (558) 450 (937) 1800 (2186) 2725 (2749)	TF: 457 (475) 253 (375) 1659 (2500) 2369 (2656)	Placebo: 425 (519) 444 (840) 1761 (2046) 2629 (2533)	TF: 417 (447) 236 (349) 1575 (2382) 2228 (2535)
IPAQ categorical score, n (%) Low Moderate High	Placebo: 4 (11.8%) 21 (61.8%) 9 (26.5%)	TF: 6 (17.6%) 18 (52.9%) 10 (29.4%)	Placebo: 4 (9.1%) 29 (65.9%) 11 (25.0%)	TF: 8 (18.2%) 25 (56.8%) 11 (25.0%)
VO2 max [ml/kg/min], mean (SD)	47.7 (5.5)		46.2 (6.0)

BMI, physical activity, and IPAQ were assessed during both study periods (visit 3 and 7) and summary statistics for the placebo and TF supplementation period reported separately. BMI, body mass index; IPAQ, International Physical Activity Questionnaire; MET, metabolic equivalent of task; TF, turmeric formulation.

3.2. Primary outcome: muscle soreness

Figure 2(a) shows the trajectory of muscle soreness for 72 hours post-exercise for male participants, with a trend toward lower soreness with TF at 72 hours (adjusted mean [SE] for TF: 13.5 [2.9] mm vs. placebo: 18.3 [3.0] mm, difference from placebo = −4.8 [2.7] mm, p = 0.0776). All assessed muscle soreness parameters (absolute values, AUC_72 h, and change from pre-exercise) for the male participants and the totality of participants are shown in Table 3. Both for male participants and the totality of participants, there were no significant differences between TF and placebo in absolute soreness and change from pre-exercise soreness at any timepoint. AUC_72 h was not significantly different between TF and placebo, in males and totality of participants, however, in the male subgroup with a soreness change from pre-exercise ≥30 mm, there was a trend toward significance (adjusted mean [SE] for TF: 2424.6 [262.2] mm∙h vs. placebo: 2907.4 [273.1] mm∙h, difference from placebo = 482.8 [275.0] mm∙h, p = 0.0984).

Figure 2.

Adjusted means and standard errors of muscle soreness reported on a visual analog scale (VAS) over 72 hours post-exercise (a) and percentage of recovery from maximal muscle soreness at 72 hours post-exercise (b) in male participants supplementing with a turmeric formulation (TF) or placebo.

Table 3.

Muscle soreness of the quadriceps of male participants and totality of participants.

	Muscle soreness reported visual analog scale [mm, mm∙h for AUC72 h]
	males		totality of participants
	placebo	TF	placebo	TF
0 h post-exercise	27.7 (2.9)	26.9 (2.9)	22.5 (12.0; 31.8)	22.3 (15.8; 32.0)
24 h post-exercise	29.8 (2.9)	27.6 (2.9)	20.3 (14.0; 33.0)	26.8 (16.5; 35.0)
48 h post-exercise	30.4 (2.9)	27.6 (2.9)	20.5 (12.5; 48.3)	25.5 (12.0; 48.0)
72 h post-exercise	18.3 (3.0)	13.5 (2.9)a	10.0 (4.5; 24.0)	9.0 (4.0; 23.5)
AUC72 h	1545 (962; 2310)	1651 (1065; 2665)	1509 (877; 2309)	1651 (1065; 2688)
Change from pre- to 0 h post-exercise	18.2 (2.6)	20.4 (2.6)	15.8 (4.3; 27.3)	16.5 (10.5; 26.3)
Change from pre- to 24 h post-exercise	20.3 (2.6)	21.1 (2.6)	14.0 (7.3; 27.5)	20.8 (10.0; 29.5)
Change from pre- to 48 h post-exercise	20.9 (2.6)	21.1 (2.6)	13.5 (6.0; 38.5)	18.3 (6.5; 37.0)
Change from pre- to 72 h post-exercise	8.7 (2.6)	7.0 (2.6)	3.0 (0.0; 17.5)	4.0 (−0.5; 14.5)

Adjusted mean (standard error) reported for mixed models on repeated measure including product group, sequence, sex for models on the totality of participants, supplementation period, timepoint on the supplementation period (not in AUC models), and product group × timepoint (not in AUC models) as fixed effects and participant nested sequence as random effect. Median (interquartile range) reported (in italics) if the adequacy of the model could not be confirmed and carryover effect was not significant, tested with Wilcoxon Signed-Rank test without adjustment of the variable. AUC, area under the curve; TF, turmeric formulation.

^aAdjusted mean (standard error) of difference from placebo: −4.8 (2.7), p = 0.0776.

The percentage of recovery from maximal post-exercise soreness at 72 hours with TF supplementation was significantly different from placebo in the male participants (adjusted mean [SE] for TF: −65.4% [4.3%] vs. placebo: −54.7% [4.4%], difference from placebo = −10.7% [4.3%], p = 0.0184, Figure 2b) and in the totality of participants (adjusted mean [SE] for TF: −63.8% [3.9%] vs. placebo: −55.9% [3.9], difference from placebo = −7.9% [3.6%], p = 0.0346). To note, the maximum soreness was not significantly different between TF and placebo in the male participants (adjusted mean [SE] for TF: 35.0 [3.1] mm vs. placebo: 36.6 [3.1] mm, difference from placebo = −1.6 [2.5] mm, p = 0.5373) and the totality of participants (adjusted mean [SE] for TF: 36.3 [2.7] mm vs. placebo: 34.7 [2.7] mm, difference from placebo = 1.6 [2.6] mm, p = 0.5439).

3.3. Secondary outcomes

3.3.1. Muscle damage

Circulating levels of CK were highly variable, and there were no significant differences between TF and placebo in the male participants and the totality of participants (Figure 3 and Supplemental Table S1).

Figure 3.

Medians and interquartile ranges (a) and Tukey boxplots of area under the curve (AUC) from pre-exercise to 72 hours post-exercise (b) of creatine kinase in male participants supplementing with a turmeric formulation (TF) or placebo.

3.3.2. Muscular function

3.3.2.1. Quadriceps muscular function

Significant differences in change from pre-exercise to 24 hours post-exercise were found between TF and placebo in male participants for isokinetic peak torque (adjusted mean [SE] for TF: −9.2 [4.2] Nm vs. placebo: −20.2 [4.2] Nm, difference from placebo = 11.0 [4.9] Nm, p = 0.0275, Figure 4(a)) and isokinetic max rep work (adjusted mean [SE] for TF: −11.1 [4.3] J vs. placebo: −22.7 [4.3] J, difference from placebo = 11.6 [4.9] J, p = 0.0195, Figure 4(b)), and in the totality of participants for isokinetic max rep work (adjusted mean [SE] for TF: −10.8 [4.0] J vs. placebo: −19.2 [4.0] J, difference from placebo = 8.4 [4.0] J, p = 0.0405). Complete listings of all assessed timepoints and AUC are provided in Table 4 for male participants and in Supplemental Table 2 for the totality of participants.

Figure 4.

Adjusted means and standard errors of isokinetic peak torque (a) and isokinetic max rep work (b) compared to pre-exercise in male participants supplementing with a turmeric formulation (TF) or placebo.

Table 4.

Muscular function and performance of male participants.

	Isokinetic peak torque [Nm, Nm∙h for AUC72 h]		Isokinetic max rep work [J, J∙h for AUC72 h]		Isokinetic power [W, W∙h for AUC72 h]		Isometric peak torque [Nm, Nm∙h for AUC72 h]		Peak jump power [W, W∙h for AUC72 h]		Jump height [cm, cm∙h for AUC72 h]		Jump velocity [m/s, m/s∙h for AUC72 h]
	placebo	TF	placebo	TF	placebo	TF	placebo	TF	placebo	TF	placebo	TF	placebo	TF
0 h post-exercise	188.1 (162.1; 210.5)	183.1 (157.9; 206.3)	194.8 (163.9; 215.7)	190.5 (158.6; 222.0)	118.5 (100.3; 131.9)	113.3 (99.7; 127.5)	208.0 (9.6)	217.7 (9.6)c	924. 5 (821.3; 1003.3)	917.2 (823.7; 1017.9)	26.8 (23.1; 30.1)	26.1 (23.7; 29.9)	2.29 (2.13; 2.43)	2.26 (2.16; 2.42)
24 h post-exercise	178.7 (162.6; 203.0)	181.8 (168.4; 204.5)	190.7 (177.0; 214.0)	195.4 (170.9; 221.6)	112.5 (100.8; 128.6)	114.3 (105.7; 131.9)	227.7 (9.7)	233.3 (9.6)	916.5 (824.8; 989.5)	931.1 (825.9; 1001.1)d	25.9 (22.0; 29.7)	25.9 (23.6; 30.7)i	2.26 (2.07; 2.41)	2.26 (2.15; 2.45)j
48 h post-exercise	183.6 (158.2; 209.9)	181.5 (163.3; 210.1)	196.7 (175.4; 218.6)	197.8 (166.3; 223.5)	115.8 (108.2; 129.1)	115.1 (99.9; 136.1)	222.4 (9.6)	229.9 (9.6)	894.6 (807.1; 996.6)	938.8 (832.9; 1003.7)e	25.7 (22.8; 30.2)	27.2 (23.2; 30.6)	2.25 (2.12; 2.43)	2.31 (2.13; 2.45)
72 h post-exercise	188.1 (168.1; 220.0)	181.0 (163.3; 225.5)	196.6 (177.1; 228.3)	203.2 (175.6; 239.9)	119.9 (108.8; 130.9)	119.5 (109.1; 145.8)	239.0 (9.7)	243.9 (9.6)	952.0 (832.0; 1024.7)	954.3 (838.9; 1024.5)	28.1 (23.9; 31.6)	26.9 (24.2; 30.9)	2.35 (2.17; 2.49)	2.29 (2.18; 2.46)
AUC72 h	13749 (12171; 15464)	13673 (11921; 15263)	14152 (13147; 16013)	14551 (12404; 16728)	8608 (7880; 9594)	8333 (7638; 9865)	16,507 (696)	17,000 (693)	67,177 (1810)	68,296 (1807)f	1967 (67)	2009 (67)	167.3 (2.9)	169.4 (2.9)
Change from pre- to 0 h post-exercise	−16.4 (4.2)	−10.4 (4.2)	−22.2 (4.3)	−18.3 (4.3)	-8.6 (−20.9; −1.8)	-7.8 (−17.1; 0.7)	−32.1 (5.3)	−23.1 (5.3)	6.3 (−22.0; 18.3)	-1.1 (−28.2; 19.0)	−0.2 (0.4)	−0.4 (0.4)	0.01 (−0.05; 0.05)	-0.01 (−0.07; 0.04)
Change from pre- to 24 h post-exercise	20.2 (4.2)	9.2 (4.2)a	22.7 (4.3)	11.1 (4.3)b	13.5 (26.4; 2.0)	8.7 (14.3; 1.4)	12.4 (5.3)	7.5 (5.3)	-21.1 (46.9; 13.4)	-4.1 (18.6; 6.9)g	1.1 (0.4)	0.4 (0.4)	-0.06 (0.12; 0.03)	-0.02 (0.03; 0.02k
Change from pre- to 48 h post-exercise	−17.0 (4.2)	−13.5 (4.2)	−19.0 (4.3)	−16.4 (4.3)	-8.3 (−26.6; −3.8)	-9.7 (−19.0; 2.5)	−17.8 (5.3)	−10.8 (5.3)	-5.7 (−47.0; 14.0)	2.8 (−26.9; 23.8)h	−0.9 (0.4)	−0.1 (0.4)	-0.02 (−0.11; 0.03)	-0.01 (−0.07; 0.05)
Change from pre- to 72 h post-exercise	−11.3 (4.2)	−3.2 (4.2)	−13.5 (4.3)	−6.0 (4.3)	-8.5 (−18.2; 5.6)	-4.2 (−9.6; 2.1)	−0.8 (5.4)	3.2 (5.3)	16.2 (−15.7; 34.6)	7.5 (−16.6; 21.2)	0.8 (0.4)	0.3 (0.4)	0.03 (−0.04; 0.08)	0.02 (−0.04; 0.05)

Adjusted mean (standard error) reported for mixed models on repeated measure including product group, sequence, supplementation period, timepoint on the supplementation period, and product group × timepoint as fixed effects and participant nested sequence as random effect. Median (interquartile range) reported (in italics) if the adequacy of the model could not be confirmed and sequence (carryover effect) was not significant, tested with Wilcoxon Signed-Rank test without adjustment of the variable. TF, turmeric formulation.

^aAdjusted mean (standard error) of significant difference from placebo: 11.0 (4.9), p = 0.0275.

^bAdjusted mean (standard error) of significant difference from placebo: 11.6 (4.9), p = 0.0195.

^cAdjusted mean (standard error) of difference from placebo: 9.7 (5.5), p = 0.0827.

^dSignificantly different from placebo p = 0.0445.

^eDifference from placebo p = 0.0625.

^fAdjusted mean (standard error) of difference from placebo: 1119 (607), p = 0.0746^gDifference from placebo p = 0.0933.

^hDifference from placebo p = 0.0692.

ⁱDifference from placebo p = 0.0748.

^jDifference from placebo p = 0.0734.

^kDifference from placebo p = 0.0811.

3.3.2.2. Vertical jump performance

Significant differences were found between TF and placebo in male participants in vertical jump peak power at 24 hours post-exercise (median [IQR] for TF: 931.1 [825.9; 1001.1] W vs. placebo: 916.5 [824.8; 989.5] W, p = 0.0445, Figure 5). All other vertical jump performance parameters of male participants assessed 24 hours after exercise did not differ significantly between TF and placebo, but several trends were observed (Table 4). Complete listings of all assessed timepoints and AUC are provided in Table 4 for male participants and in Supplemental Table 3 for the totality of participants.

Figure 5.

Tukey boxplots of vertical jump power in male participants supplementing with a turmeric formulation (TF) or placebo.

3.3.2.3. Range of motion

Knee flexion ROM for male participants and the totality of participants is listed in Supplemental Table 4. At 72 hours after exercise, there was a significant difference between TF and placebo in male participants (median [IQR] for TF: 138° [135°; 141°] vs. placebo: 137° [134°; 140°], p = 0.0095) and the totality of participants (adjusted mean [SE] for TF: 139° [1°] vs. placebo: 138° [1°], difference from placebo = 1° [0°], p = 0.0434).

3.3.3. Wellness and wellbeing

While the measures of wellness and wellbeing are not directly related to EIMD, muscle damage or function, we aimed to assess the influence of the TF on overall wellbeing, as it is known that turmeric may impact mood and stress, which could, in turn, influence exercise-related outcomes. There were no significant differences in overall wellness and wellbeing, as well as in all subscores, between TF and placebo in the male participants (Supplemental Table S5) and the totality of participants (Supplemental Table S6).

3.3.4. Perceived exertion during exercise

There were no significant differences in RPE during exercise, assessed as change from pre-exercise, between TF and placebo in the male participants and the totality of participants (Supplemental Table S7).

3.4. Safety outcomes

A total of three participants (6.8%) experienced a TEAE during the TF period of the study (back pain, muscle spasms, syncope). One participant (2.3%) experienced a TEAE during the placebo period (cough). All adverse events (AE) were of mild or moderate intensity. No serious AEs were reported in this study and no AE resulted in discontinuation of the study product. Two AEs were assessed as related to the study product (muscle spasms, back pain). No gastrointestinal discomfort was reported during the study period. All AEs and their severity are listed in Supplemental Table S23.

4. Discussion

This randomized, double-blind, placebo-controlled, crossover clinical trial evaluated the efficacy of a highly bioavailable dried colloidal turmeric suspension (TF) on DOMS and muscular function recovery in moderately active adults after unaccustomed EIMD. While there was no significant difference between TF and placebo in the primary endpoint (muscle soreness AUC_72 h), a significant 10.7% (SE 4.3%, p = 0.0184) improvement over placebo in recovery from maximal muscle soreness was observed at 72 hours after EIMD with TF. Furthermore, TF resulted in significantly better muscular function recovery (isokinetic peak torque and max rep work) and muscle performance (peak jump power) 24 hours after EIMD. This time point coincides with the peak loss of muscular function, highlighting the potential of turmeric supplementation to mitigate functional decline following EIMD. RPE during exercise, CK levels as an indicator for muscle damage, and perceived wellness and wellbeing were not significantly different between TF and placebo.

The exercise effect on DOMS in this study was lower than expected when the protocol for EIMD was designed (adjusted mean [SE] immediate exercise effect was 20.4 [2.6] for TF and 18.2 [2.6] mm for placebo, and exercise effect after 24 hours was 21.1 [2.6] for TF and 20.3 [2.6] mm for placebo). This resulted in lower overall DOMS levels (adjusted mean [SE] maximal soreness in male participants was 35.0 [3.1] mm for TF and 36.6 [3.1] mm for placebo) compared to studies reporting significant differences in DOMS with turmeric supplementation [29,32,33,35]. The previously published short-term studies investigating the effect of turmeric supplementation after a downhill run found reduced muscle soreness [25,27]. It is crucial to consider the methodological variations in downhill running protocols since they can result in different levels of EIMD. Key factors include the grade, running speed, and exercise duration. For example, previous studies have indicated that steeper slopes and higher running speeds are associated with greater EIMD, as evidenced by increased levels of DOMS and elevated biomarkers such as CK [7]. The previous turmeric supplementation studies employed longer running duration (45 versus 30 minutes at the anaerobic threshold [25] or maximal maintainable effort [27], while the grade was the same (−10%). However, besides the EIMD protocol, another major difference is that the curcuminoid dosages were 4.4 [25] and 2.8 times [27] than in the present study. Running downhill is generally less energetically demanding than running uphill, as potential energy is transformed into kinetic energy. In our study, participants ran at 70% VO₂ max, which may not have been sufficient to elicit the expected levels of DOMS in the downhill context. Therefore, we recommend that future studies increase the running speed to better compensate for the effects of gravity on acceleration.

To adjust for the low DOMS levels in this study, the recovery from maximal soreness was investigated and found to be significantly improved with TF compared to placebo (adjusted mean [SE] for difference from placebo = −10.7% [4.3%], p = 0.0184). Furthermore, the subgroup analysis in male participants with higher DOMS levels (soreness change from pre-exercise ≥30 mm) revealed a trend toward significance in the muscle soreness AUC_72 h, with an effect size that was 1.12 times higher than hypothesized (482.8 vs. 432 mm∙h hypothesized). Finally, the SD of the effect size of the primary outcome was higher than assumed in the sample size calculation (1013.0 vs. 708 mm∙h for TF, 1350.1 vs. 396 mm∙h for placebo). Therefore, the primary outcome might have reached significance with a higher level of muscle soreness and/or a larger sample size.

A recent systematic review and meta-analysis found a positive effect of turmeric supplementation on muscle soreness at 72 and 96 hours after exercise [53]. Even though the included studies also used turmeric supplements formulated for improved absorption, they differed from our study in that they used high curcuminoid dosages (≥150 mg/day curcumin) or long-term (8 weeks) supplementation [26,29–32]. Although we used a dose that was only half of the acceptable daily intake for a person weighing 60 kg, we found significantly improved DOMS recovery. Similarly, Basham et al. observed a significant reduction in muscle soreness with a low long-term (four weeks) dose of a preparation of fresh turmeric rhizome (1500 mg/day, ~70 mg/day curcuminoids) [37]. In contrast, studies using standard turmeric extracts in high doses (5700 mg/day curcuminoids combined with piperine or 1060 mg/day curcuminoids alone) found no significant effects on DOMS [28,36].

Improved DOMS recovery by TF is supported by improved muscular function 24 hours after exercise, including significantly better jump power and smaller decreases in isokinetic peak torque and max rep work. Despite an observed 23% reduction in the AUC_72 h of CK, there were no significant differences in CK levels, potentially attributable to the high variability of this parameter [7]. Similarly, a meta-analysis conducting subgroup analysis according to study design and train status did not find a significant effect on CK concentration in crossover trials or trials in trained participants [53]. Comparable to the population in the present study, the trained participants included in the meta-analysis engaged in either at least 150 minutes of moderate-intensity aerobic activity or 30 minutes of vigorous-intensity aerobic activity per week [37], light to moderate regular physical activity including sports training (e.g. football and basketball, but not lower limb resisted exercise) [28], or were elite rugby players [36].

The clinical implications of the improved recovery with TF supplementation found in this study may include an earlier return to training or competition in acute recovery scenarios in recreational athletes. For recreational athletes and moderately active individuals, reduced muscle soreness might support motivation and improve discipline [54,55].

No deaths, serious AEs, or withdrawals due to AEs occurred in this study. All AEs were of mild or moderate intensity and only two were deemed to be related to TF. No notable or clinically meaningful changes in participants’ anthropometrics or vitals were detected during the study. Therefore, TF was found to be safe and well tolerated in this study.

The strengths of this clinical trial include the randomized, double-blind, placebo-controlled, crossover design, and the conduct and statistical analyses by independent contract research organizations. Furthermore, the participant-reported primary outcome was supported by objectively measured secondary outcomes. Limitations in the design of this clinical trial included the protocol of EIMD, which did not induce the expected levels of muscle soreness and damage to obtain distinct soreness and CK levels. Future downhill running protocols should consider increasing running speed, a steeper slope, and a longer exercise duration [7]. In addition, increasing the investigated post-exercise window to 96 hours would be beneficial in future studies [7]. At the time of study design, available published data permitted a power calculation solely for male participants, necessitating that primary analyses be conducted exclusively in this group. This limits the generalizability of the findings to women. Nonetheless, female participants were included as exploratory outcomes. Furthermore, this investigation was conducted in a free-living setting, which presents both advantages and disadvantages. The advantages include the ability to observe participants in their natural environment, leading to greater generalizability to real-world scenarios. However, the disadvantages may involve less control over external variables, such as dietary intake and physical activity levels, which could introduce variability in the data. Finally, the acute nature of the study limits conclusions regarding the long-term adaptations to exercise. Given that this study focused on downhill running, the generalizability of these results to other forms of exercise, such as resistance training, remains to be determined.

In conclusion, supplementation with a highly bioavailable dried colloidal suspension of curcuminoids can accelerate DOMS recovery and could attenuate muscular function loss 24 hours after unaccustomed eccentric exercise in young, moderately active, male adults. The efficacy in females, other age groups (e.g. seniors), and highly trained athletes striving for optimized long-term training adaption remains to be investigated in separate, adequately powered and correspondingly designed clinical and training studies.

Funding Statement

This research was funded by Givaudan France Naturals. KAS is an employee of Givaudan International SA. JL, SN, and PFB are employees of Givaudan France Naturals. They (KAS, JL, SN, and PFB) contributed to experimental design and write-up but were not involved in any data collection or analysis. RT, TW and SM were supported through a service agreement with Givaudan France Naturals.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15502783.2025.2568048