Vol.:(0123456789)1 3 European Journal of Nutrition (2022) 61:3835–3855 https://doi.org/10.1007/s00394-022-02943-7 REVIEW Effect of curcumin supplementation on exercise‑induced muscle damage: a narrative review K. Nanavati1  · K. Rutherfurd‑Markwick2  · S. J. Lee3  · N. C. Bishop4  · A. Ali1 Received: 29 October 2021 / Accepted: 15 June 2022 / Published online: 13 July 2022 © The Author(s) 2022 Abstract Curcumin, a natural polyphenol extracted from turmeric, is a potent antioxidant and anti-inflammatory agent. In the past few decades, curcumin’s ability to impact chronic inflammatory conditions such as metabolic syndrome, arthritis, and cancer has been widely researched, along with growing interest in understanding its role in exercise-induced muscle damage (EIMD). EIMD impacts individuals differently depending on the type (resistance exercise, high-intensity interval training, and run- ning), intensity, and duration of the exercise. Exercise disrupts the muscles’ ultrastructure, raises inflammatory cytokine levels, and can cause swelling in the affected limb, a reduction in range of motion (ROM), and a reduction in muscular force-producing capacity. This review focuses on the metabolism, pharmacokinetics of various brands of curcumin supple- ments, and the effect of curcumin supplementation on EIMD regarding muscle soreness, activity of creatine kinase (CK), and production of inflammatory markers. Curcumin supplementation in the dose range of 90–5000 mg/day can decrease the subjective perception of muscle pain intensity, increase antioxidant capacity, and reduce CK activity, which reduces muscle damage when consumed close to exercise. Consumption of curcumin also improves muscle performance and has an anti-inflammatory effect, downregulating the production of pro-inflammatory cytokines, including TNF-α, IL-6, and IL-8. Curcumin may also improve oxidative capacity without hampering training adaptations in untrained and recreationally active individuals. The optimal curcumin dose to ameliorate EIMD is challenging to assess as its effect depends on the curcumin concentration in the supplement and its bioavailability. Keywords Curcumin · Pharmacokinetics · Inflammation · Muscle soreness · Oxidative stress · Antioxidant Introduction Curcumin, chemically known as 1,7-bis(4-hydroxy- 3-methoxyphenyl)-1,6-heptadiene-3,5-dione or diferu- loylmethane [1], is isolated from the plant Curcuma longa [2]. Over the past few decades, curcumin has been widely researched for its antioxidant and anti-inflammatory prop- erties in numerous chronic and malignant diseases such as metabolic syndrome [3], arthritis [4, 5], and cancer [6–8]. However, there has been a growing interest in understand- ing the effect of curcumin on exercise-induced muscle dam- age (EIMD) in recent years. EIMD affects all individuals depending upon the type, intensity, and duration of the exer- cise they undertake and training status of the individual [9, 10]. Resistance training [11], high-intensity interval training [12], trail running [13, 14], and downhill running [15] con- tribute to EIMD, leading to ultrastructural muscular disrup- tion and an increase in inflammatory cytokine levels. Swell- ing of the affected limb, decreased range of motion (ROM), * A. Ali a.ali@massey.ac.nz K. Nanavati k.nanavati@massey.ac.nz K. Rutherfurd-Markwick k.j.rutherfurd@massey.ac.nz S. J. Lee s.j.lee@massey.ac.nz N. C. Bishop n.c.bishop@lboro.ac.uk 1 School of Sport, Exercise, and Nutrition, Massey University, Auckland, New Zealand 2 School of Health Sciences, Massey University, Auckland, New Zealand 3 School of Food and Advanced Technology, Massey University, Auckland, New Zealand 4 School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK http://orcid.org/0000-0001-8638-3185 http://orcid.org/0000-0002-8815-3786 http://orcid.org/0000-0003-0634-1984 http://orcid.org/0000-0001-6221-3907 http://orcid.org/0000-0002-6093-1435 http://crossmark.crossref.org/dialog/?doi=10.1007/s00394-022-02943-7&domain=pdf 3836 European Journal of Nutrition (2022) 61:3835–3855 1 3 and impaired muscle force-producing capacity which can result from EIMD are undesirable [16–18]. Curcumin has been shown to attenuate muscle soreness, improve performance, reduce blood levels of inflammatory markers, and enhance endogenous oxidative capacity post- exercise [19–26]. Muscle damage is prominent post-exercise due to the release of prostaglandins under the influence of cyclooxygenase (COX-1 and COX-2), which contributes to redness, swelling, and pain at the site of damage [27, 28]. Curcumin downregulates the expression of COX-2 and thus decreases the release of prostaglandins [29] which in turn reduces muscle damage [19–23]. Exercise, and production of prostaglandins under the influence of COX-2, leads to increased membrane permeability [30, 31] and releases cre- atine kinase (CK) into the interstitial fluid and then circu- lation via the lymphatic system [32] and indicates muscle damage. Although research on the chronic effects of cur- cumin supplementation is limited, data so far have not dem- onstrated any ergolytic effects as observed following supple- mentation with other natural antioxidants such as vitamin C and E supplementation. A detailed review [36] on the effects of vitamin C and vitamin E supplementation on exercise per- formance suggests that these antioxidant supplementations may impair neuromuscular adaptation by affecting muscle mitochondrial biogenesis and muscle hypertrophy [33]. Clinical trials indicate consumption of curcumin close to exercise downregulates cyclooxygenase that influences membrane permeability [31] and offers a membrane-pro- tective effect by altering the structure of the cell membrane to improve its integrity [34]. Curcumin also helps in reduc- ing inflammation by hindering the activation of nuclear factor-kappa B (NF-κB), suppressing the activation and phosphorylation of Janus kinase/signal transducers and activators of transcription (JAK/STAT) proteins, and inhib- iting mitogen-activated protein kinase (MAPK) signalling that releases inflammatory markers such as tumour necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and interleukin-6 (IL-6) at the site of damage [35]. In addition, the downregu- lation of NF-κB can also lead to the elevation of antioxidant responses by activation of nuclear factor erythroid 2-related factor 2 (NRF2) [36]. NRF2 regulates the synthesis of anti- oxidant proteins that protect against oxidative damage trig- gered by injury and inflammation [37]. Curcumin can be tolerated without any associated toxic- ity at 8000 mg/day [38]. However, poor aqueous solubility [39] and low bioavailability [40] of curcumin have led to the development of different curcumin formulations such as nanoparticles [41], phytosomes [42], micelles [43], and phospholipid complexes [44]. Each formulation contains varying levels of curcuminoids and has a different rate of absorption, making it difficult to conclude a single recom- mended dose. Nevertheless, different curcumin formu- lations have been shown to effectively reduce EIMD and inflammation in doses varying from 90 mg/day to 5000 mg/ day [21, 25]. This narrative review evaluates the different curcumin formulations and their effect on EIMD, inflam- mation, and oxidative markers. Methods The databases SCOPUS, Medline (PubMed), and Web of Science (WOS) were searched using a mix of Medical Subject Headings (MeSH) and free words for key concepts related to curcumin, muscle, exercise, inflammation, recov- ery, along with bioavailability of curcumin as follows: (“cur- cumin” OR “turmeric”) AND (“muscle damage” OR “delay onset muscle soreness” OR “DOMS” OR “inflammation” OR “inflammatory” OR “inflammatory markers” OR “oxi- dative stress”) AND (“exercise”). For articles on other natu- ral antioxidants and their effect on exercise performance, search terms included (“antioxidants”), (“vitamin E and C”), (“tart cherry juice”), (“natural extracts”) AND (“exercise” OR “exercise-induced muscle damage” OR “exercise perfor- mance’’), between December 2020 and March 2021. Only full-text articles (written in English) describing human trials were included for review. Curcumin metabolism The bioavailability of curcumin is low due to its water insolubility and poor metabolism in the small intestine and liver, where it undergoes extensive reductive and conjugative metabolism and is finally eliminated through the gall bladder [45]. The metabolism of curcumin can be divided into two phases (Fig. 1). Phase I comprises the reduction of its double bonds to dihydrocurcumin, tetrahydrocurcumin, hexahydro- curcumin, and octahydrocurcumin by reductases in entero- cytes and hepatocytes [40]. For phase II, both curcumin and its metabolites from phase I undergo conjugation with sul- phate at its phenolic site in the hepatic and intestinal cytosol. In addition, metabolites also undergo glucuronidation via UDP-glucuronosyltransferase in the intestinal and hepatic microsomes [40]. Alternatively, curcumin can be metabo- lised by intestinal microbiota, such as Escherichia coli to tetrahydrocurcumin with the help of an NADPH-dependent reductase and by Blautia sp. MRG-PMF1 (anaerobic bacte- rial strain) that facilitates curcumin demethylation to form demethylcurcumin and bis-demethylcurcumin [46]. Pharmacokinetics of curcumin supplements Absorption, distribution, hepatic and intestinal metabolism, and excretion regulate the bioavailability of ingested cur- cumin [45]. In addition, the physicochemical properties of each curcumin formulation and the dose, along with its rate 3837European Journal of Nutrition (2022) 61:3835–3855 1 3 of degradation in the lumen, lipophilicity, and gastric empty- ing time, help determine the body’s pharmacokinetics [47]. Some studies have assessed plasma curcumin levels after hydrolysis of blood plasma samples, however, such hydrol- ysis prior to extraction masks the amount of free, bioac- tive curcumin and total curcuminoids as compared to non- hydrolysed samples [50]. When treated with the enzymes β-glucuronidase and sulfatase, curcumin generates glucu- ronide curcumin and curcumin sulphate, which are the pri- mary circulating forms of curcumin but are physiologically inactive conjugates. This obscures the free bioactive cur- cumin and overestimates the amount of curcumin detected, thus providing incorrect and misleading results regarding the bioavailability of the formulation [48]. This highlights the importance of reporting free curcumin in the plasma without hydrolysis of the sample. Plasma samples obtained from studies involving Theracurmin [41], Meriva [42], and NovaSol [43] were all hydrolysed using β-glucuronidase/ sulfatase before analysis and thus the bioavailability results should be viewed with caution. Overview of bioavailability of different curcumin formulations Information on dosage, study type, and study population of six different formulations, namely Theracurmin [41], Meriva [42], NovaSol [43], CurQfen [49], Longvida [44], and Curcumin C3 Complex [50], along with their pharma- cokinetic parameters are presented in Tables 1 and 2 [47]. The evidence from human trials suggests that formulating curcumin improves systemic exposure and increases area under curve (AUC) and maximum blood concentration of curcumin, and thus, increases the bioavailability of curcumin (Cmax) [41–44, 49, 50]. The use of gum ghatti in a water-soluble formulation called Theracurmin [41] led to a preparation of a stable water-soluble complex that contributed to colloidal disper- sion and enhanced gastrointestinal absorption [41]. A dose of 30 mg of Theracurmin containing 3.6 mg curcuminoids showed a 27-fold improvement in its AUC (0–6 h), with a Tmax of 1 h. Another water-soluble curcumin: NovaSol [43] demonstrated the highest Cmax along with 185-fold better bioavailability compared to its native form, with a single dose of 500-mg of curcuminoids. The improved relative bioavailability was contributed by the micellar-based cur- cumin formulation with Tween 80 (non-ionic surfactant and Fig. 1 Metabolic pathways of curcumin 3838 European Journal of Nutrition (2022) 61:3835–3855 1 3 Table 1 Composition of different curcumin formulations Formulation name Formulation Technology Curcuminoid concentration Ingredients Theracurmin [41] Colloidal nanoparticles 12% 12% curcuminoids, 46% glycerine, 4% gum ghatti, 38% water Meriva® [42] Phytosome 18–20% Curcumin, soy lecithin, microcrystalline cellulose NovaSol [43] Liquid micelles 6% 93% Tween 80, and 7% curcumin powder CurQfen [49] Soluble fibre blend Not defined Fenugreek soluble fibre blend, and 40% curcumin Longvida® [44] Solid lipid curcumin particle 20–30% Solid lipid curcumin particle lipids, phosphatidylcholine, and 20% curcumin Curcumin C3 Com- plex® + Bioperine [50] Not applicable Not defined Bioperine and curcuminoids Table 2 Pharmacokinetic parameters of curcumin from the different curcumin-based formulations and reference (unformulated curcumin) in human studies a Mean ± standard deviation b Mean ± standard error of mean * AUC 0–24 ⁑ AUC 0–12 † AUC 0–6 Control: unformulated curcumin, AUC area under the drug concentration–time curve, Cmax maximum drug concentration, Tmax time at maximum drug concentration, ND not defined Formulation Clinical study design Population Intervention Dose Sample hydrolysis Cmax (ng/mL) Tmax (h) AUC 0–t (ng h/ mL) Theracurmin [41] Randomised, crossover Asian 14 (8 males, 6 females) 44.1 ± 8.5 years Formulationa 30 mg thera- curmin Hydrolysed 29.5 ± 12.9 1 113 ± 61* Controla 30 mg curcumin powder 1.8 ± 2.0 6 4.1 ± 7.0* Meriva® [42] Randomised, double- blind, crossover Caucasian 9 (8 males, 1 female) Formulationb 376 mg curcumin Hydrolysed 206.9 ± 54.9 2.7 ± 0.3 1336.0 ± 357.1* Controlb 1799 mg curcumin 14.4 ± 4.2 6.9 ± 2.2 202.8 ± 53.8* NovaSol [43] Randomised, single‐blind crossover Caucasian 23 (10 males, 13 females) 23 ± 3 years Formulationa 500 mg cur- cuminoids Hydrolysed 1189.1 ± 518.7 1.1 ± 0.4 4474.7 ± 1675.2⁑ Controla 500 mg cur- cuminoids 2.6 ± 4.9 7.5 ± 8.2 24.1 ± 42.6⁑ CurQfen [49] Crossover Indian 8 (males) 25–50 years Formulationa 600 mg curcumin Not hydro- lysed 0.4 ± 0.2 (µg/g) 1 8100 ± 287* (µg h/g) Controla 1000 mg curcumin 0.02 ± 0.01 (µg/g) 0.5 510 ± 123* (µg h/g) Longvida® [44] Randomised, double- blind, crossover Indian 6 (males) 18–40 years Formulationb 650 mg cur- cuminoids Not hydro- lysed 22.4 ± 1.9 2.4 ± 0.4 95.3 ± 4.6* Controlb 650 mg cur- cuminoids < 1 ND ND Curcumin C3 Com- plex® + Bio- perine [50] Randomised, crossover Indian 8 (males) 20–26 years Formulationb 2000 mg cur- cumin with bioperine Not hydro- lysed 180 ± 30 0.69 ± 0.07 80 ± 10† Controlb 2000 mg curcumin 6 ± 5 1 4† 3839European Journal of Nutrition (2022) 61:3835–3855 1 3 emulsifier) that could deliver most of the curcumin to the intestinal wall for absorption by escaping the phase separa- tion in the gastrointestinal tract [43]. Schiborr et al. [43] also observed that less than 0.2% of the oral dose of Novasol curcumin was excreted in urine within 24 h, and concluded that the remaining >98.8% of the ingested curcumin was either excreted via the bile and faeces or may have been distributed to body tissues where it may potentially exert biological activities. Meriva [42], a formulation using natu- ral curcuminoids and lecithin (phosphatidylcholine phyto- some complex of soy) in the ratio of 2:1 along with two parts of microcrystalline cellulose yielded the highest Tmax at 2.7 ± 1 h for a dose of 376 mg of curcuminoids, and 29-fold higher curcuminoid absorption compared to the unformu- lated curcumin. Interestingly, the authors [42] concluded that lecithin favoured the bioavailability of demethoxycurcumin as its plasma content was found to be higher than curcumin itself, despite its low concentration in the formulation. The formulation of fenugreek fibre and 40% curcumin called CurQfen [51] yielded the highest AUC over 24 h at a dose of 1500 mg (equivalent to 600 mg curcumin). The use of soluble fibre in the formulation produced a non-digestible gel hydrocolloid that could ferment in the colon, prevent curcumin degradation in the gastrointestinal tract, and retard curcumin release resulting in a lag time of more than 5 h and less than 30% the total release after 24 h [51]. Thus, the fibre–curcumin complex contributed to improved and delayed curcumin absorption [51]. The curcumin formulation named Longvida [44] incor- porated solid lipid curcumin particles (SLCP; 650 mg) in their formulation. A single dose of 130–195 mg of curcumin showed a Tmax of 2.4 h. The SLCP is a proprietary formula and comprises of curcumin mixed with soy lecithin contain- ing purified phospholipids, docosahexaenoic acid (DHA), and/or vegetable stearic acid, ascorbyl (vitamin C) esters, and inert ingredients. The improved bioavailability of SLCP compared to unformulated curcumin is linked to key param- eters such as curcumin/lipid/antioxidant ratio, globule-size distribution, and stability [51]. Consumption of a combination of curcumin and piper- ine in the Curcumin C3 Complex + Bioperine resulted in a 20-fold increase in plasma curcumin concentrations com- pared to the control formulation with the lowest Tmax of 0.69 h. Piperine is a P-glycoprotein and a uridine diphos- phate-glucuronosyltransferase (UGT) inhibitor, and is sug- gested to improve absorption of curcumin by decreasing the efflux in the intestine and increasing the freely avail- able curcumin in the systemic circulation [50]. Although curcumin was not observed in the plasma from 3 to 6 h, the bioavailability improved by 1.5 times compared to that of unformulated curcumin [50]. Plasma curcumin concentration in exercise trials Several studies [22, 23, 25, 52, 53] that investigated the effect of curcumin on exercise-induced inflammatory and oxidative stress markers also evaluated plasma curcumin concentration post-supplementation. All studies [22, 23, 25, 52, 53] observed an increase in plasma curcumin con- centration post-supplementation at time points ranging from 2 h to 1–4 days (Table 3). The studies also concluded that supplementation with curcumin resulted in an increase in oxidative capacity [25], improvements in visual analogue scale for muscle soreness [23] and daily analysis of life demands questionnaire [52], and a decrease in CK levels [22, 53] (Table 4). It is difficult to compare and evaluate the plasma cur- cumin concentration as studies by Tanabe et al. [22, 53] did not describe the sample preparation process and studies by Takahashi et al. [25], Sciberras et al. [52], and Tanabe et al. [23] hydrolysed their plasma samples and, therefore, the amount of curcumin in the plasma [48], may have been overestimated. Difficulties in comparing the effects of different pharmacokinetic characteristics of curcumin supplements on muscle damage markers It is challenging to understand how the measured differ- ences in pharmacokinetic characteristics (Cmax, Tmax, and AUC) of the specific supplements may relate to changes in inflammatory markers and attenuation of muscle damage. One key contributing factor is that although pharmacokinetic and exercise trials have both been carried out using the same formulations (Theracurmin [41] and Meriva [42]) different doses have been used for the exercise [23, 25, 43] versus the pharmacokinetic studies [41, 42]. In addition, some researchers have not measured the plasma curcumin con- centrations post-supplementation, or do not clearly state the curcumin concentrations in the supplement, also making it challenging to compare results [24]. Others have hydrolysed the plasma samples before analysis [23, 25, 43], thus over- estimating the true concentration of curcumin in the blood and making it difficult to accurately correlate any observed changes in levels of inflammatory markers to plasma cur- cumin levels. Finally, although some researchers [54] have reported that curcumin supplementation increased working capacity at the fatigue threshold and delayed the onset of neuromuscular fatigue, they did not analyse common inflam- matory markers such as IL-6, TNF-α, and CK, also hinder- ing comparisons between studies [54]. 3840 European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 3 S um m ar y of p la sm a cu rc um in c on ce nt ra tio n in st ud ie s e xa m in in g th e eff ec t o f c ur cu m in in ta ke o n ex er ci se -in du ce d m us cl e da m ag e (E IM D ) A ut ho r a nd y ea r Po pu la tio n D ur at io n C ur cu m in su pp le m en t D os ag e Pl as m a cu rc um in c on ce nt ra - tio n Sa m pl e hy dr ol ys is Ta ka ha sh i e t a l., 2 01 3 [2 5] 26 m al es (2 6. 8 ± 2. 0  ye ar s) (r ec re at io na lly a ct iv e) 1  da y Th er ac ur m in C on tro l Pl as m a cu rc um in c on ce n- tra tio ns in th e do ub le cu rc um in su pp le m en ta tio n tri al 2  h a fte r e xe rc is e w er e si gn ifi ca nt ly h ig he r t ha n th os e in th e si ng le c ur cu m in su pp le m en ta tio n tri al H yd ro ly si s 90  m g/ da y 2  h be fo re e xe rc is e 18 0  m g/ da y 2  h be fo re a nd im m ed ia te ly af te r e xe rc is e Ta na be e t a l., 2 01 8 [2 2] 10 m al es (2 8. 5 ± 3. 4  ye ar s) (u nt ra in ed ) 7  da ys Th er ac ur m in Ex pe rim en t 1 — 18 0  m g (9 0  m g tw ic e a da y— at br ea kf as t a nd d in ne r) co ns um ed fo r 7  d ay s b ef or e ex er ci se Pl as m a cu rc um in c on - ce nt ra tio ns si gn ifi ca nt ly de cr ea se d fro m b as el in e (3 8. 8 ± 17 .8  n g  m L− 1 ) to 1 , 3 , 5 , a nd 7  d ay s af te r e xe rc is e (1 0. 2 ± 5. 4, 5. 0 ± 2. 7, 0 .1 ± 0. 4, a nd 0. 1 ± 0. 2  ng   m L− 1 , r es pe c- tiv el y) N o m en tio n of th e pr oc es s us ed 10 m al es (2 9. 0 ± 3. 9  ye ar s) (u nt ra in ed ) Ex pe rim en t 2 — 18 0  m g (9 0  m g tw ic e a da y— at br ea kf as t a nd d in ne r) C on su m ed fo r 7  d ay s a fte r ex er ci se Pl as m a cu rc um in si g- ni fic an tly in cr ea se d fro m b as el in e (5 .3 ± 6. 1  ng   m L− 1 ) t o 1  da y (5 0. 6 ± 25 .6  n g  m L− 1 ), an d th en m ai nt ai ne d a hi gh p la sm a cu rc um in co nc en tra tio n th ro ug h 3, 5 , an d 7  da ys a fte r e xe rc is e (5 8. 5 ± 37 .1 , 4 2. 2 ± 46 .0 , an d 41 .1 ± 29 .2  n g  m L− 1 , re sp ec tiv el y) Ta na be e t a l., 2 01 9 [2 3] 8 m al es (2 8. 0 ± 3. 2  ye ar s) (u nt ra in ed ) 7  da ys Th er ac ur m in C R- 03 3P C on tro l – H yd ro ly si s 8 m al es (2 8. 8 ± 3. 6  ye ar s) (u nt ra in ed ) PR E— 18 0  m g (9 0  m g tw ic e a da y— at br ea kf as t a nd d in ne r) C on su m ed fo r 7  d ay s b ef or e ex er ci se A t b as el in e an d at 1 –3  d af te r e xe rc is e, th e pl as m a cu rc um in c on ce nt ra tio n of th e PR E gr ou p w as si g- ni fic an tly h ig he r t ha n th at in th e co nt ro l a nd P O ST gr ou ps 8 m al es (2 9. 8 ± 3. 4  ye ar s) (u nt ra in ed ) PO ST — 18 0  m g (9 0  m g tw ic e a da y— at br ea kf as t a nd d in ne r) C on su m ed fo r 4  d ay s a fte r ex er ci se A t 1 –4  d a fte r e xe rc is e, th e pl as m a cu rc um in c on ce n- tra tio n of th e PO ST g ro up w as si gn ifi ca nt ly h ig he r th an th at o f t he c on tro l a nd PR E gr ou ps 3841European Journal of Nutrition (2022) 61:3835–3855 1 3 Effect of curcumin on exercise‑induced muscle damage Intense training can lead to EIMD and can cause swelling, reduced ROM, and loss of muscle strength in the affected limb [16–18]. EIMD is characterised by muscular ultrastruc- tural disruption that increases the release of inflammatory cytokines from myofibers and consequently increases their circulating levels. Muscle soreness increases from about 24 to 48 h post-exercise and decreases gradually from 72 h post- exercise. The activity of CK, a marker of EIMD, increases from 24 h onwards post-exercise and is sustained over a period of 7 days post-exercise [30]. Curcumin ingestion results in the attenuation of the release of inflammatory and oxidative markers, muscle pain, muscle performance, and CK levels by modulating inflam- matory signalling cascades. Table 4 contains information from studies investigating the effect of curcumin on EIMD. Out of the 15 studies discussed below, the majority of par- ticipants in the trials were young physically active males 20–40 years of age. In addition, studies investigating the effect of curcumin supplementation on EIMD employed exercise protocols that led to different levels of muscle damage and assessed a variety of parameters, thus making it difficult to directly compare results and provide defini- tive conclusions as to whether curcumin supplementation is effective. Muscle soreness EIMD leads to delayed onset muscle soreness, associ- ated with muscle pain, resulting in reductions in muscle strength and function and impairing physical function for several days post-exercise [55]. Damage to skeletal muscle activates phospholipase A2, which leads to the removal of arachidonic acid from the cell membrane [56]. Arachidonic acid is converted to prostaglandin G2 (PGG2) under the influ- ence of cyclooxygenase (COX-1 and COX-2) and then to prostaglandin H2 (a common precursor to all prostaglandins) [27]. Prostaglandins are pro-inflammatory and cause red- ness, swelling (due to increased membrane permeability), and pain at the site of muscle damage [28]. Curcumin down- regulates the expression of COX-2 and thus, decreases the release of prostaglandins [29] which in turn reduces muscle soreness [19–23]. Studies [19–23] have shown significantly lower levels of muscle soreness when curcumin was consumed approxi- mately 24 h before or after exercise. Consumption of 150 mg of curcumin (Theracurmin) immediately post-exercise resulted in a lower visual analogue scale (VAS) score for perceived muscle soreness compared to placebo at 48 and 72 h after unaccustomed squat exercises in untrained males [19]. Similarly, consumption of 180 mg of Theracurmin Ta bl e 3 (c on tin ue d) A ut ho r a nd y ea r Po pu la tio n D ur at io n C ur cu m in su pp le m en t D os ag e Pl as m a cu rc um in c on ce nt ra - tio n Sa m pl e hy dr ol ys is Ta na be e t a l., 2 01 5 [5 3] 14 m al es (2 3. 5 ± 2. 3  ye ar s) (U N TR A IN ED ) Si ng le d os e Th er ac ur m in 30 0  m g 15 0  m g— 1  h be fo re e xe rc is e 15 0  m g— 12  h a fte r e xe rc is e Pl as m a cu rc um in c on ce nt ra - tio n in cr ea se d fro m b as el in e (0 .0 4 ± 0. 07  n g/ m L) to 12 7. 7 ± 14 4. 6, 8 5. 7 ± 51 .6 , 8. 6 ± 5. 5, 2 .2 ± 1. 4 an d 0. 9 ± 0. 6  ng /m L at 0 , 2 4, 48 , 7 2 an d 96  h a fte r e xe r- ci se , r es pe ct iv el y N o m en tio n of th e pr oc es s us ed Sc ib er ra s e t a l., 2 01 5 [5 2] 11 m al es (3 5. 5 ± 5. 7  ye ar s) (tr ai ne d) 4  da ys M er iv a® 50 0  m g w ith m id da y m ea l fo r 3  d ay s a nd 5 00  m g ju st be fo re e xe rc is e M ea n ± S D (r an ge ) c ur cu m in co nc en tra tio n ob ta in ed w as 79 .7 ± 26 .3  n g/ m l ( 50 .7  n g/ m L to 1 25 .5  n g/ m L) H yd ro ly si s 3842 European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 4 S um m ar y of st ud ie s e xa m in in g th e eff ec t o f c ur cu m in in ta ke o n ex er ci se -in du ce d m us cl e da m ag e (E IM D ) A ut ho r a nd y ea r Po pu la tio n St ud y de si gn D ur at io n C ur cu m in su pp le - m en t D os ag e C ur cu m in oi ds co nt en t A ct iv ity ty pe K ey fi nd in gs Ta ka ha sh i e t a l., 20 13 [2 5] 26 m al es (2 6. 8 ± 2. 0  ye ar s) (r ec re at io na lly ac tiv e) D ou bl e- bl in d, p la - ce bo -c on tro lle d, co un te rb al an ce d cr os so ve r d es ig n 1  da y Th er ac ur m in Pl ac eb o N A W al ki ng o r r un ni ng at 6 5% V ̇O 2 m ax on a tr ea dm ill fo r 60  m in ↑ G PX ↑ d- RO M ’s 90  m g/ da y 2  h be fo re e xe rc is e 10 % c ur cu m in , 2 % cu rc um in oi ds w ith ou t c ur cu m in ↑ Pl as m a cu rc um in ↑ BA P ↑ G SH † TB A R S † G SS H † SO D 18 0  m g/ da y 2  h be fo re a nd im m ed ia te ly a fte r ex er ci se N ak ho sti n- Ro oh i et  a l., 2 01 6 [1 9] 10 m al es (2 5. 0 ± 1. 6  ye ar s) (u nt ra in ed ) R an do m is ed c on - tro lle d tri al — do u- bl e- bl in d cr os so ve r Si ng le d os e Th er ac ur m in 15 0  m g Im m ed ia te ly p os t- ex er ci se 10 % c ur cu m in , 2 % cu rc um in oi ds w ith ou t c ur cu m in U na cc us to m ed sq ua t ex er ci se s ↓ CK ↓ VA S fo r p ai n ↑ TA C Ta na be e t a l., 2 01 8 [2 2] 10 m al es (2 8. 5 ± 3. 4  ye ar s) (u nt ra in ed ) D ou bl e‐ bl in d cr os so ve r d es ig n 7  da ys Th er ac ur m in 18 0  m g (9 0  m g tw ic e a da y— at b re ak fa st an d di nn er ) C on su m ed fo r 7  da ys b ef or e ex er ci se N ot d efi ne d 30 m ax im al e cc en - tri c co nt ra ct io ns o f th e el bo w fl ex or s at a n an gu la r ve lo ci ty o f 1 20 °/ s ↓ Pl as m a cu rc um in ↓I L- 8 10 m al es (2 9. 0 ± 3. 9  ye ar s) (u nt ra in ed ) 18 0  m g (9 0  m g tw ic e a da y— at b re ak fa st an d di nn er ) C on su m ed fo r 7  da ys a fte r ex er ci se ↑ Pl as m a cu rc um in ↓ VA S fo r m us cl e so re ne ss ↓ CK Ta na be e t a l., 2 01 9 [2 3] 8 m al es (2 8. 8 ± 3. 6  ye ar s) (u nt ra in ed ) R an do m is ed , co nt ro lle d, si ng le - bl in d, p ar al le l de si gn st ud y 7  da ys Th er ac ur m in C R- 03 3P PR E— 18 0  m g (9 0  m g tw ic e a da y— at b re ak fa st an d di nn er ) C on su m ed fo r 7  da ys b ef or e ex er ci se 30 % c ur cu m in , 6 % ot he r c ur cu m i- no id s 30 m ax im al e cc en - tri c co nt ra ct io ns o f th e el bo w fl ex or s at a n an gu la r ve lo ci ty o f 1 20 °/ s ↑ Pl as m a cu rc um in a t ba se lin e † CK 8 m al es (2 9. 8 ± 3. 4  ye ar s) (u nt ra in ed ) 4  da ys PO ST — 18 0  m g (9 0  m g tw ic e a da y— at b re ak fa st an d di nn er ) C on su m ed fo r 4  da ys a fte r ex er ci se ↓ VA S fo r m us cl e so re ne ss † CK 3843European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 4 (c on tin ue d) A ut ho r a nd y ea r Po pu la tio n St ud y de si gn D ur at io n C ur cu m in su pp le - m en t D os ag e C ur cu m in oi ds co nt en t A ct iv ity ty pe K ey fi nd in gs Ta na be e t a l., 2 01 5 [5 3] 14 m al es (2 3. 5 ± 2. 3  ye ar s) (u nt ra in ed ) R an do m is ed , c ro ss o- ve r d es ig n Si ng le d os e Th er ac ur m in 30 0  m g 15 0  m g— 1  h be fo re ex er ci se 15 0  m g— 12  h a fte r ex er ci se N ot d efi ne d 50 m ax im al e cc en - tri c co nt ra ct io ns o f th e el bo w fl ex or s at a n an gu la r ve lo ci ty 1 20 °/ s ↑ Pl as m a cu rc um in ↓ M V C to rq ue ↓ CK † IL -6 a nd T N F- α M cF ar lin e t a l., 20 16 [2 4] 16 (5  M , 1 1 F) (2 0 ± 1  ye ar s) (u nt ra in ed ) R an do m is ed c on - tro lle d 6  da ys Lo ng vi da 40 0  m g 48  h b ef or e ex er ci se an d fo r 7 2  h af te r N ot d efi ne d 6 se ts o f 1 0 re p- et iti on s o f t he le g pr es s e xe rc is e w ith a b eg in ni ng lo ad se t a t 1 10 % of th ei r e sti m at ed 1R M † Su bj ec tiv e qu ad ri- ce ps p ai n †A D L ↓C K ↓T N F- α ↓I L- 8 † IL -1 0 † IL -6 Sc ib er ra s e t a l., 20 15 [5 2] 11 m al es (3 5. 5 ± 5. 7  ye ar s) (tr ai ne d) D ou bl e- bl in d ra n- do m is ed c ro ss ov er 4  da ys M er iv a® 50 0  m g w ith m id da y m ea l f or 3  d ay s an d 50 0  m g ju st be fo re e xe rc is e N ot d efi ne d Pa rti ci pa nt s e xe r- ci se d fo r 2  h a t a po w er o ut pu t eq ui va le nt to 9 5% of th ei r l ac ta te th re sh ol d † IL -6 , I L- 10 ↑ D A LD A Q ue sti on - na ire (b et te r t ha n us ua l) F. D ro bn ic e t a l., 20 14 [7 0] C — 9 m al es (3 2. 7 ± 12 .3  y ea rs ) (tr ai ne d) R an do m is ed , p la - ce bo -c on tro lle d, si ng le -c en tre , si ng le -b lin d pi lo t tri al 4  da ys M er iv a® 1  g tw ic e a da y 48  h p rio r t o ex er - ci se a nd c on tin ue d fo r 2 4  h af te r ex er ci se 20 0  m g/ do se M od ifi ed d ow nh ill ru nn in g te st— ru n- ni ng a t a c on st an t sp ee d fo r 4 5  m in af te r a 1 0- m in w ar m -u p on tre ad m ill †C R P † hs C R P † M C P- 1 † FR A P † G Px † CK ↓ IL -8 † In te ns ity o f p ai n P— 10 m al es (3 8. 1 ± 11 .1  y ea rs ) (tr ai ne d) Jä ge r e t a l., 2 01 9 [5 7] 63 (3 1  M , 3 2 F) (2 1 ± 2  ye ar s) (tr ai ne d) D ou bl e- bl in d, ra n- do m is ed , p la ce bo - co nt ro lle d pa ra lle l de si gn 8  w ee ks C ur cu W IN ® Lo w -d os e gr ou p 25 0  m g th ric e a da y (b re ak fa st/ lu nc h/ di nn er ) 50  m g of c ur cu m i- no id s 45 -m in d ow nh ill ru n at a – 1 5% gr ad e an d sp ee d eq ui va le nt to 6 5% V O 2M ax a fte r 5- m in w ar m u p ↑ Su bj ec tiv e m us cl e pa in (a nt er io r, po s- te rio r) a ll gr ou ps † Su bj ec tiv e (to ta l) m us cl e pa in in hi gh -d os e gr ou p 1  h an d 24  h p os t- ex er ci se † M ax im um b en di ng to rq ue a nd b en di ng po w er in lo w -d os e gr ou p H ig h- do se g ro up 10 00  m g th ric e a da y (b re ak fa st/ lu nc h/ di nn er ) 20 0  m g of c ur cu m i- no id s Pl ac eb o N A 3844 European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 4 (c on tin ue d) A ut ho r a nd y ea r Po pu la tio n St ud y de si gn D ur at io n C ur cu m in su pp le - m en t D os ag e C ur cu m in oi ds co nt en t A ct iv ity ty pe K ey fi nd in gs M cA lli ste r e t a l., 20 20 [6 6] 14 m al es (2 1– 30  y ea rs ) (tr ai ne d) D ou bl e- bl in de d, ra nd om is ed , cr os so ve r d es ig n 4  da ys C ur cu Fr es h 15 00  m g/ da y 10 00  m g at b re ak fa st an d 50 0  m g at d in - ne r f or d ay s 1 , 2 an d 3 an d 45  m in be fo re te sti ng o n da y 4 69  m g of c ur cu m i- no id s D ua l s tre ss c ha l- le ng es ta sk th at co ns ist ed o f 35  m in o f s te ad y- st at e ex er ci se at a w or kl oa d co rr es po nd in g to 60 % V O 2 p ea k w ith m en ta l s tre ss ch al le ng es † G H S ↓S O D ↓ A O PP ↓ H 2O 2 S. B as ha m e t a l., 20 19 [2 6] 20 m al es (2 1. 7 ± 2. 9  ye ar s) (tr ai ne d) R an do m is ed , do ub le -b lin de d, pl ac eb o- co n- tro lle d, c ro ss ov er 28  d ay s C ur cu Fr es h 15 00  m g/ da y 10 00  m g at b re ak fa st an d 50 0  m g at d in - ne r f or 2 8  da ys 69  m g of c ur cu m i- no id s 22 5 re pe tit io ns o f s it an d st an d us in g an ae ro bi c ste p be nc h in 1 5  m in ↓ CK ↓ VA S † TA C † M D A † TN F- α A m al ra j e t a l., 2 02 0 [2 0] 30 (1 2  M , 1 8 F) (3 6 ± 11  y ea rs ) (tr ai ne d) R an do m is ed , p la - ce bo -c on tro lle d, do ub le -b lin d 4  da ys C ur ei t 50 0  m g/ da y (c on su m ed o n da y 2, 3 an d 4 of st ud y) N ot d efi ne d D ow nh ill ru nn in g fo r 4 5  m in † CK ↓ VA S fo r m us cl e pa in D el ec ro ix e t a l., 20 17 [6 1] 16 m al es (2 0. 7 ± 1. 4  ye ar s) (tr ai ne d) R an do m is ed , p la - ce bo -c on tro lle d, ba la nc ed c ro ss ov er de si gn 4  da ys M G D n at ur e 2  g cu r- cu m in + 20  m g Pi pe rin e co ns um ed th re e tim es a d ay ev er y 6  h be tw ee n 8 am a nd 1 0  pm O n ex er ci se da y— 45  m in be fo re , i m m ed i- at el y po st- a nd 6  h po st- ex er ci se N ot d efi ne d 25 re pe tit io ns o ve r 25  m o f o ne -le g ju m ps o n an 8 % do w nh ill sl op e † Is om et ric p ea k to rq ue † C on ce nt ric p ea k to rq ue † Ju m p pe rfo rm an ce † CK † M us cl e so re ne ss a t an y tim e po in t H er ric k et  a l., 2 02 0 [5 4] 47 (2 5  M , 2 2 F) (2 1. 0 ± 2. 6  ye ar s) (u nt ra in ed ) G 1: 1 8 (C + F EN ) G 2: 1 4 (F EN ) G 3: 1 5 (P ) R an do m is ed , d ou - bl e- bl in d, p la ce bo - co nt ro lle d, p ar al le l de si gn 28  d ay s C ur Q fe n 50 0  m g/ da y cu r- cu m in + 30 0  m g fe nu gr ee k di et ar y fib re (g al ac to m an - na ns ) C on su m ed in th e m or ni ng b ef or e ea tin g 19 0  m g of c ur cu m in M ax im al g ra de d ex er ci se te st on a cy cl e er go m et er ↑ Ph ys ic al w or k- in g ca pa ci ty a t t he fa tig ue th re sh ol d ↑ de la y th e on se t of n eu ro m us cu la r fa tig ue † V ̇O 2p ea k †T im e to e xh au sti on 3845European Journal of Nutrition (2022) 61:3835–3855 1 3 (90 mg twice a day at breakfast and dinner) for 7 days after exercise resulted in a significant reduction in muscle sore- ness 3–6 days after eccentric exercise in untrained males compared to the placebo group [22]. A study on untrained males reported a significantly lower perceived muscle soreness VAS score for the upper arm and elbow joint at 3 and 4 days after consumption of 180 mg Theracurmin CR-033P (90 mg twice a day at breakfast and dinner) for 4 days after eccentric elbow flexion [23]. Intake of 500 mg/day (Cureit; consumed on days 2, 3, and 4 after exercise) by trained participants resulted in a decreased pain VAS score from 2.90 to 1.17 in the curcumin group com- pared to a smaller decrease in the placebo group [20]. More- over, administration of 2500 mg twice daily of curcumin for 2.5 days before exercise, and then 2500 mg twice daily for 2.5 days after exercise, resulted in moderate to large effect size reductions in muscle pain during single-leg squat and gluteal stretch at 24 and 48 h [21]. Not all studies show clear benefits of curcumin sup- plementation in reducing muscle soreness. For example, one study implementing 56 days of supplementation with 200 mg of curcuminoids (1000 mg curcumin by CurcuWIN) in trained individuals indicated not statistically significant reductions in muscle soreness. Compared to the placebo and low-dose (50 mg) curcumin groups, the treatment group showed non-significant reductions of 26, 20, and 8% lower muscle soreness immediately, 24, and 48 h post-exercise (conducted on 57 ± 3 days), respectively. Further research would be required to determine if the non-significant recov- ery benefits from curcumin may have been due to the final supplementation dose being administered 24 h prior to the exercise and the lack of supplementation after exercise [57]. A wide range of curcumin doses were administered across these studies with differences in formulation, frequency, and timing of ingestion relative to exercise, along with the train- ing status of the participants and the exercise protocol used that may have influenced the extent of muscle soreness post- completion of exercise. In addition, VAS for soreness is a subjective measure, varying from individual to individual, thus potentially influencing the results. Nonetheless, studies have reported lower levels of soreness when 180–2500 mg/ day curcumin was consumed immediately after exercise and/ or within at least 24 h before and/or after exercise [21, 23]. Muscle performance NF-κB is the transcriptional control for myokines (cytokines synthesised and released during muscular contractions) that are involved in post-exercise inflammatory responses [58]. Overuse of joints contributes to high mechanical stress and generates bone and cartilage extracellular matrix fragments that are recognised by receptors expressed by innate immune cells. Cell activation mediated by this process stimulates the Ta bl e 4 (c on tin ue d) A ut ho r a nd y ea r Po pu la tio n St ud y de si gn D ur at io n C ur cu m in su pp le - m en t D os ag e C ur cu m in oi ds co nt en t A ct iv ity ty pe K ey fi nd in gs N ic ol e t a l., 2 01 5 [2 1] 17 m al es (3 3. 8 ± 5. 4  ye ar s) (tr ai ne d) D ou bl e- bl in d ra nd om is ed -c on - tro lle d cr os so ve r 5  da ys Eu ro fin s s ci en tifi c in c. 50 00  m g/ da y 5 ca ps ul es tw ic e da ily fo r 2 .5  d ay s pr io r t o ex er ci se , th en 5 c ap su le s tw ic e da ily fo r 2. 5  da ys a fte r ex er ci se N ot d efi ne d 7 se ts o f 1 0 ec ce n- tri c si ng le -le g pr es s r ep et iti on s on a le g pr es s m ac hi ne a ↓ V A S fo r m us cl e pa in ↓ CK ↓I L- 6 (a t 2 4  h re la tiv e to b as el in e) ‡T N F- α ↑ St at ist ic al ly si gn ifi ca nt in cr ea se ↓ St at ist ic al ly si gn ifi ca nt d ec re as e † C ha ng e w ith ou t s ta tis tic al si gn ifi ca nc e ‡ N o im pa ct a m od er at e to la rg e eff ec t C C ur cu m in G ro up , P P la ce bo G ro up , M M al es , F F em al es , G PX g lu ta th io ne p er ox id as e, d -R O M ’s re ac tiv e ox yg en m et ab ol ite s, BA P bi ol og ic al a nt io xi da nt p ot en tia l, G SH a nd G SS H re du ce d an d ox id is ed g lu ta th io ne , T BA RS th io ba rb itu ric a ci d- re ac tiv e su bs ta nc es , S O D s up er ox id e di sm ut as e, C K c re at in e ki na se , V AS v is ua l a na lo gu e sc al e, T AC to ta l a nt io xi da nt c ap ac ity , I L- 8 In te r- le uk in -8 , M VC M ax im al v ol un ta ry c on tra ct io n, A D L A ct iv iti es o f d ai ly li vi ng so re ne ss , T N F- α Tu m ou r N ec ro si s F ac to r-α , I L- 10 In te rle uk in -1 0, IL -6 In te rle uk in -6 , D AL D A Q ue sti on na ire D ai ly A na ly si s of L ife D em an ds Q ue sti on na ire , C RP C -R ea ct iv e Pr ot ei n, M C P- 1 m on oc yt e ch em oa ttr ac ta nt p ro te in -1 , F RA P Fe rr ic R ed uc in g A nt io xi da nt P ow er , A O PP a dv an ce d ox id at io n pr ot ei n pr od uc ts , H 2O 2 h yd ro ge n pe ro xi de , M D A m al on di al de hy de , F EN F en ug re ek 3846 European Journal of Nutrition (2022) 61:3835–3855 1 3 activation of NF-κB, resulting in secretion of inflammatory cytokines such as IL-1 and TNF-α, which contribute to tis- sue damage [59]. Curcumin blocks the signalling pathway of NF-κB, reducing the inflammatory response, decreas- ing swelling, while improving joint mobility and stiffness (assessed via maximum voluntary contraction (MVC) force and ROM) [22, 23, 53]. Intake of 90 mg curcumin (Theracurmin) twice a day (breakfast and dinner) for 7 days in untrained males resulted in significant improvements in MVC torque and ROM com- pared to the placebo group 3–7 days after eccentric exercise [22]. In a similar study, consumption of 90 mg curcumin (TheracurminCR-033P) twice a day (breakfast and dinner) for 4 days after eccentric exercise resulted in improvements in ROM of the elbow joint at 3–4 days in untrained males compared to the placebo group. The increases in the degree of ROM coincided with improvements in muscle soreness, indicating that the two could be related. However, another study [23] involving 30 maximal eccentric contractions of elbow flexors showed no significant differences in MVC torque between curcumin and placebo groups at all time points [23]. Muscle regeneration begins on day 3 after exer- cise [60], and since the follow-up of the recovery period was only 4 days, this time period may have been insufficient to establish the effect of curcumin on MVC torque [23]. One study examining the effect of 50 mg of curcumin (in the form of 250 mg of CurcuWIN®) or 200 mg of curcumin (in the form of 1000 mg of CurcuWIN®) over 56 days in physically active men and women reported that curcumin could prevent decreases in peak extension torque values observed at 1 and 24 h after muscle-damaging exercise (downhill running) [57]. However, changes in isokinetic peak and average flexion torque, peak extension and flexion power, peak and average peak torque failed to yield statisti- cal significance at 1, 24, 48, and 72 h post-exercise. One of the limitations of the supplementation protocol used was conducting the exercise protocol after discontinuing cur- cumin supplementation and it is possible that continuing supplementation may have prevented a decrease in the per- formance measures [57]. Ingestion of 150 mg of curcumin (Theracurmin) imme- diately and 12 h after eccentric exercise in untrained males led to a decrease in MVC from baseline [53]. However, the decrease in MVC was significantly smaller (33.0 ± 8.0%) in the curcumin group than in the placebo group (40.0 ± 9.1%) immediately after exercise and 48–96 h after exercise. The smaller decrease in MVC indicates that intake of curcumin leads to a lower level of muscle damage than the placebo group. However, ROM significantly decreased through all time points from the baseline in the curcumin group and there was no significant interaction effect for the changes compared to the placebo groups [53]. This suggests that supplementation with 150 mg Theracurmin twice a day for only one day is inadequate to improve ROM post-exercise. In a randomised crossover trial, elite rugby players, consuming 6 g of curcumin and 60 mg of piperine (MGD Nature, Brandérion, France) each day starting 48 h pre-exer- cise and continuing until 48 h post-exercise experienced a moderately smaller loss of mean power output during the 6-s sprint compared to the control group 24 h after exercise [61]. However, this result was counterbalanced by the absence of effect from curcumin supplementation on isometric peak torque, concentric peak torque, and jump performance at all time points. This was possibly because the EIMD protocol consisted of 25 repetitions over 25 m of one-leg jumps on an 8% downhill slope, which required a greater neuromuscular recruitment pattern compared to isokinetic and isometric tests [61]. Furthermore, a possible limitation of this study could be the quick muscle damage recovery kinetics (train- ing adaptations) which could be a result of the population tested, i.e. elite rugby players [61]. Another study examining the effects of curcumin in combination with fenugreek soluble fibre (CUR + FEN) or fenugreek soluble fibre alone (FEN) on the physical work- ing capacity at the fatigue threshold (PWCFT), peak oxygen consumption (V ̇O2 peak), and time to exhaustion (Tlim) on a graded exercise test in untrained subjects for 28 days [54], showed no effect of curcumin supplementation on VȮ2 peak or Tlim. However, the PWCFT was greater after combined supplementation with curcumin and FEN compared with a placebo in ~20% of subjects [54]. Thus, based on the results obtained by Tanabe et al. [23], improvements in both MVC force and ROM in untrained males could be a result of consumption of 180 mg of cur- cumin in divided doses (two times a day) across 4–7 days post-eccentric exercise [23]. Creatine kinase Muscle creatine kinase (CK-MM), a marker of EIMD, is one of the three isoforms of CK, and is present at places within the muscle fibre where ATP consumption is high [62]. Eccentric muscle contractions exceeding the muscle’s resistance result in perforations in the sarcolemma and dam- age to the sarcomeres, leading to increased membrane per- meability [30, 62, 63], and release of CK into the interstitial fluid that then enters circulation via the lymphatic system [32]. In addition, the production of prostaglandins under the influence of COX-2 leads to vascular hyperpermeability, which could further aid release of CK [31]. Curcumin supplementation indirectly lowers plasma CK activity in several ways. First, curcumin in the blood offers a membrane-protective effect by altering the structure of the membrane [34] and improving membrane integrity, thus reducing CK release into the blood [64]. Second, curcumin 3847European Journal of Nutrition (2022) 61:3835–3855 1 3 can suppress the regulation of the COX-2 pathway, reducing prostaglandin release and hence influence vascular perme- ability, ultimately decreasing the intracellular–intravascular flow of CK [31]. Lastly, curcumin’s antioxidant properties can suppress the activity of ROS generated during muscle contractions that would ordinarily contribute to muscle dam- age via CK release [25, 65]. Several studies [19, 21, 22, 24, 26, 53] have observed sig- nificantly lower CK activity in the curcumin supplemented group at doses of 150–5000 mg/day in both trained [21] and untrained individuals [24, 53]. Single-dose investiga- tions with an intake of 150 mg curcumin (Theracurmin) post-eccentric exercise showed a lower rise in CK activity immediately 0, 24, 48, and 72 h post-exercise compared to the placebo group [19]. In addition, CK activity was signifi- cantly lower in the curcumin group compared to the placebo group at 24 h [19]. Intake of 180 mg of curcumin (Thera- curmin) for 7 days (90 mg twice a day, at breakfast and din- ner) after exercise in untrained men also resulted in lower CK activity compared to the placebo group [22]. Consump- tion of 300 mg curcumin (Theracurmin) in divided doses (150 mg 1 h before exercise and 150 mg 12 h after exer- cise) showed a significantly smaller peak CK activity for the curcumin group (3398 ± 3562 IU/L) compared to placebo (7684 ± 8959 IU/L) and lower activity at 48, 72 and 96 h compared to baseline CK levels [53]. Similarly, 1500 mg/ day (CurcuFresh) of curcumin resulted in significantly lower CK activity (199.62 U/L in the curcumin group compared to 287.03 U/L in the placebo group) [66]. Supplementation with 5000 mg/day of curcumin (Eurofins Scientific Inc.) for 5 days (5 capsules twice daily for 2.5 days before exercise, then 5 capsules twice daily for 2.5 days after exercise) in trained men showed a small reduction in CK activity at 24 and 48 h (−22 to 29%; ±21 to –22%) compared to the base- line values [21]. Lower CK activity in the curcumin groups across the studies may suggest that myofibril damage due to exercise was attenuated by curcumin ingestion [53]. Curcumin supplementation before and/or after exercise can decrease CK activity post-exercise. However, the magni- tude of the reduction varies from study to study. Several fac- tors may have contributed to the differing outcomes, includ- ing the training status of the participants, exercise protocol, duration of the study, the timing of ingestion of the curcumin supplement, and the formulation of the curcumin supple- ment itself (including treatments and other ingredients that affect the rate of absorption). Inflammatory markers Curcumin exerts anti-inflammatory actions by hindering the activation of NF-κB, suppressing the activation and phos- phorylation of JAK/STAT proteins, and inhibiting MAPK signalling that contribute to the production of inflammatory markers such as TNF-α, IL-6, and IL-8 at the site of muscle damage [35]. TNF-α: The effect of curcumin supplementation on reduc- ing TNF-α levels in the blood has been evaluated in several studies [21, 22, 24, 26, 53], with equivocal observations reported. No significant differences in plasma TNF-α levels were found between the curcumin and placebo trials when 150 mg [53] and 180 mg of curcumin [22] were consumed by untrained males following elbow flexor eccentric exer- cise [22, 53]. This could be because the exercise protocol involved small muscle mass and was short in duration, and, therefore, did not affect the inflammatory cytokine levels in the blood [67]. In addition, as TNF-α has a very short half- life (15–30 min), plasma concentrations do not always reflect those produced by myocytes [68]. Moreover, the TNF-α lev- els were measured in the blood and not the muscle tissue. As concentrations of inflammatory markers and oxidative stress markers after exercise are different between muscle tissue and blood [69], the observation on the effect of curcumin on TNF-α levels post-exercise may be limited. In the study by McFarlin et al. [24], untrained subjects completed 6 sets of 10 repetitions of leg press exercise and consumed 400 mg/ day of curcumin 48 h before exercise, up until 72 h after exercise. They observed that TNF-α levels were significantly lower with curcumin at 1 day (− 25%), 2 days (− 23%), and 4 days (− 23%) compared to placebo and concluded that a minimum dose of 400 mg curcumin could be effective in decreasing circulating levels of TNF-α [24]. However, studies involving 1500 mg/day of curcumin supplementation (69 mg of curcuminoids) for 28 days (Cur- cuFresh) [26] and 5000 mg/day for 5 days (Eurofins Scien- tific Inc.) [21] reported no significant decrease in plasma TNF-α levels after exercise in trained males. Curcumin sup- plementation in both the studies [21, 26] was likely inef- fective because physically active individuals were recruited and the participants’ aerobic training status (150 min of moderate-intensity aerobic activity or 30 min of vigorous- intensity aerobic activity per week) offered the stimulus for adaptations that contributed to lower resting levels of TNF-α (1.2 pg/mL), thus negating any potential anti-inflammatory benefits of curcumin supplementation [26]. In addition, the authors proposed that no significant decrease in TNF-α levels was observed in the trained individuals because the exercise protocol they used (7 sets of 10 eccentric single-leg press repetitions) failed to cause sufficient muscle damage due to muscle adaptations from prior physical activity [21]. In most studies [21, 22, 53], the exercise protocol used led to only minor increases in plasma TNF-α concentrations and reported no significant differences in plasma TNF-α levels in curcumin groups compared to placebo groups. Nonethe- less, as observed for untrained individuals, a minimum of 400 mg curcumin supplementation before and after eccentric 3848 European Journal of Nutrition (2022) 61:3835–3855 1 3 exercise may result in lower increases in TNF-α levels post- eccentric exercise [24]. IL-6 and IL-8 The effect of curcumin supplementation on IL-6 and IL-8 levels before and after exercise in trained and untrained individuals has been evaluated in several studies [21, 22, 24, 53, 70]. No significant decrease in post- exercise IL-6 levels was observed in the curcumin group when compared to placebo groups when supplemented with 300 mg (Theracurmin) [53] or 400 mg of curcumin (Long- vida), respectively [24]. However, the exercise protocol cho- sen (6 sets of 10 repetitions of the leg press exercise with a beginning load set at 110% of their estimated 1-repeti- tion maximum) may not have been sufficient to increase the pro-inflammatory cytokines in the body due to the muscle mass involved and the short duration of the activity [24]. In addition, blood samples were not taken immediately after exercise but were taken at 24, 48, 72, and 96 h post-exer- cise; therefore, the researchers may have missed observing changes in IL-6 levels which typically increase from 8 to 12 h post-eccentric exercise, and return to baseline levels by 24 h post-exercise [53, 71]. In contrast, Nicol et al. [21] observed a decrease in IL-6 values in the curcumin supple- mented group (5000 mg curcumin; Eurofins Scientific Inc.) in trained participants after 7 sets of 10 eccentric single-leg press repetitions on a leg press machine at 24 h relative to immediately post-exercise [21]. However, they also observed an increase in IL-6 levels (small standardised differences) immediately post-exercise (31%; ±29%) and again at 48-h post-exercise (32%; ±29%) relative to baseline, thus, making the overall effect of curcumin supplementation unclear [21]. Supplementation with 180 mg of curcumin for 7 days prior to exercise (30 maximal eccentric contractions of the elbow flexors) in untrained males was associated with sig- nificantly lower plasma IL-8 levels 12 h after exercise than the placebo group [22]. This decrease in plasma IL-8 levels was associated with high concentrations of curcumin in the blood during and after exercise that suppressed the exercise- induced inflammatory effect [22]. However, no significant differences were observed when curcumin was ingested after exercise [22]. Conversely, intake of 400 mg/day of curcumin (Longvida) (2 days before exercise and for 3 days after exer- cise) resulted in a significantly lower IL-8 concentrations at day 1 (−21%) and day 2 (−18%) post-exercise (6 sets of 10 repetitions of leg press) compared to placebo in untrained individuals [24]. Furthermore, intake of 1 g of curcumin supplement (Meriva) twice a day 2 days before exercise and for 1 day after exercise (modified downhill running) in trained individuals also resulted in a significantly lower increase in plasma IL-8 levels 2 h post-exercise [70]. Thus, although the effect of curcumin supplementation on IL-6 levels remains unclear, curcumin intake before and after exercise may lower serum IL-8 levels in both trained and untrained individuals. Oxidative markers Reactive oxygen species are produced by a variety of extra- cellular and intracellular agents such as electron leakage from the mitochondrial respiratory chain and NADPH oxi- dases [72]. Exercise can induce oxidative stress by increas- ing oxygen utilisation up to 200-fold in active muscles and contributing to excessive amounts of ROS [73, 74], which can damage DNA, proteins, and lipids [75, 76] and affect exercise performance [77]. Reactive oxygen species contribute to oxidative stress and maintain inflammation by promoting the activation of NF-κB. During a sustained inflammatory response, accu- mulation of neutrophils within tissues provides a growth medium for producing oxidative enzymes, cytokines, and chemokines [78–80]. Curcumin can suppress the activa- tion of NF-κB and potentially lead to elevated antioxidant responses by activating NRF2 [36], which upregulates the synthesis of antioxidant proteins that protect against oxi- dative damage triggered by injury and inflammation [37]. Thus, activation of NRF2 can improve the total antioxidant capacity of the body and reduce the harmful effects of ROS [36]. In addition, the phenolic OH group of curcumin has the potential to act as a ROS scavenger and a quencher of the lipid peroxidative side chain, thus reducing the activity of lipid hydroperoxides [81]. Curcumin supplementation (Theracurmin) with 90 mg/ day (2 h before endurance exercise) and 180 mg/day (90 mg 2 h before and immediately after endurance exercise) in healthy men attenuated exercise-induced increases in the serum concentrations of derivatives of reactive oxygen metabolites (d-ROMs) and serum biological antioxidant potential (BAP), and also reduced plasma glutathione levels (GSH) post-exercise [25]. However, there were no signifi- cant increase observed in superoxide dismutase (SOD), and glutathione peroxidase (GPx) concentrations immediately after and post-2 h of exercise compared to the pre-values in both single and double curcumin supplementation groups [25]. In addition, supplementation with 150 mg curcumin (Theracurmin) after squat exercises in untrained males resulted in improved total antioxidant capacity (TAC) at 24 and 48 h post-exercise compared to the placebo group [19]. In a study [22] where curcumin (180 mg; Theracurmin) was supplemented for 7 days before and after exercise in a double-blind crossover study, no statistically significant improvements in serum concentrations of d-ROMs and BAP were observed in the curcumin and placebo groups as well as between groups over time [17]. It is possible that the exercise protocol used in this study (30 maximal eccen- tric contractions of the elbow flexors at an angular velocity of 120°/s) was insufficient to result in significant oxidative stress [22]. Similarly, curcumin supplementation (1500 mg/ day (1000 mg breakfast, 500 mg dinner); CurcuFresh) for 3849European Journal of Nutrition (2022) 61:3835–3855 1 3 28 days in trained males showed no significant improve- ments in TAC post-exercise (225 repetitions of sit and stand using aerobic step bench over 15 min) compared to the placebo. According to the authors, the lack of significant changes in TAC may be because the assay did not quantify changes in enzymatic antioxidants and had poor sensitivity [26]. In a trial comparing the effects of curcumin (1 g, Meriva, 2× per day, 2 days before, and 1 day after exercise) versus placebo on catalase (CAT) and GPx levels in aerobically trained males who completed a 2 h downhill run, levels of both enzymes tended to increase 2 h after exercise and returned towards baseline values 24 h after exercise in both curcumin and placebo groups [70]. The recruitment of aero- bically trained participants may have limited muscle damage with the exercise protocol used, thus possibly explaining limited changes in CAT and GPx activity [65]. Thus, results from two studies indicate that supplementa- tion with 90–180 mg curcumin 2 h before exercise or imme- diately after exercise may improve the antioxidant capac- ity of the body [19, 25]. However, more quality research is needed to clarify the optimal dose. Based on the studies discussed in this review, curcumin is beneficial in alleviating exercised-induced muscle damage. However, due to the vast differences in the formulations of curcumin supplements and study protocols, it is difficult to determine a single dose that would be effective in reducing various inflammatory markers and increase the antioxidant enzymes such as SOD and GPx. Table 5 summarises the timing and dose of curcumin supplementation required to improve muscle soreness and performance, inflammatory markers, and oxidative markers associated with EIMD in trained and untrained participants after eccentric and endur- ance exercise. Limitations of research and future directions The curcumin formulations discussed in this review have been developed with varying amounts of curcuminoids and different ingredients that impact their bioavailability, thus making it complicated to suggest a single optimal dose for reducing inflammation post-exercise. However, formula- tion-specific doses can be suggested based on the scientific research for each particular product. Most of the studies discussed in this review recruited young healthy participants and there are no data available for the effect of curcumin on EIMD in older adults. Older adults are of special interest as they experience sarcopenia: gener- alised loss of skeletal muscle mass and muscle strength with age. As a result, older individuals have low muscle mass, low muscle strength, and an increased body fat percent- age that contributes to chronic inflammation and oxidative stress compared to young individuals [82]. Moreover, the body composition of older individuals with sarcopenia is significantly altered compared to that of a young population. Therefore, the results from the studies based on the effect of curcumin on EIMD in young trained and untrained individu- als should not be extrapolated to a sarcopenic older popula- tion. In addition, research on the chronic effects of curcumin consumption based on specific formulations, in association with an appropriate exercise protocol are required to evalu- ate their effects on recovery from EIMD. Conclusion Curcumin is a challenging ergogenic aid to study due to its poor bioavailability and poor metabolism in the intestine and liver. However, new formulations using nanoparticles [41], phytosomes [42], micelles [43], and phospholipid complexes [44] have been developed which demonstrate improved bioavailability and their effects on EIMD have been investigated in humans. Overall, curcumin supple- mentation is most effective in reducing EIMD when con- sumed by untrained individuals. Supplementation immedi- ately after exercise and/or within at least 24 h before and/ or after exercise is highly recommended. Though the opti- mum amount of curcumin required to decrease serum IL-6 levels is still unclear, supplementation with 400–1000 mg of curcumin 1–2 times a day could be considered to aid in improving muscle performance and lowering circulat- ing IL-8 levels. To date, one study in untrained males has shown decreases in TNF-α levels post-exercise following consumption of 400 mg/day of curcumin for a period of 6 days [24]; however, more studies are needed to confirm this effect. In addition, curcumin supplementation in the range of 150–5000 mg/day has been effective in decreas- ing CK levels in both untrained and trained individuals when consumed pre- and/or post-exercise. To improve the antioxidant capacity of the body post-exercise, curcumin supplementation with 90–180 mg curcumin 2 h before exercise or immediately after exercise may be effective [19, 25]. Curcumin impacts the production of several exercise- induced inflammatory markers. However, the amount of curcumin required to elicit changes in these inflammatory markers vary significantly. In addition, as no two studies fol- low the same protocol along with the same curcumin formu- lation, it is challenging to conclude the amount of curcumin required to reduce EIMD. Author contributions KN reviewed papers, wrote, and revised the article and AA, KRM, SJL and NCB suggested improvements and reviewed the article. 3850 European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 5 S um m ar y of th e tim in g an d do se o f cu rc um in s up pl em en ta tio n re qu ire d to im pr ov e m us cl e so re ne ss a nd p er fo rm an ce , i nfl am m at or y m ar ke rs , a nd o xi da tiv e m ar ke rs a ss oc ia te d w ith ex er ci se -in du ce d m us cl e da m ag e (E IM D ) EI M D m ar ke rs a nd ox id at iv e m ar ke rs A ut ho r Tr ai ni ng st at us o f pa rti ci pa nt s Ex er ci se p ro to co l Fo rm ul at io n C ur cu m in oi ds co nt en t D ur at io n D os ag e Ti m in g of d os e M us cl e so re ne ss N ak ho sti n- Ro oh i et  a l., 2 01 6 [1 9] U nt ra in ed U na cc us to m ed sq ua t ex er ci se s Th er ac ur m in 10 % c ur cu m in , 2 % cu rc um in oi ds w ith - ou t c ur cu m in Si ng le d os e 15 0  m g Im m ed ia te ly p os t- ex er ci se Ta na be e t a l., 2 01 8 [2 2] U nt ra in ed 30 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity o f 12 0° /s Th er ac ur m in N ot d efi ne d 7  da ys 18 0  m g 90  m g tw ic e a da y at br ea kf as t a nd d in ne r, co ns um ed fo r 7  d ay s af te r e xe rc is e Ta na be e t a l., 2 01 9 [2 3] U nt ra in ed 30 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity o f 12 0° /s Th er ac ur m in 30 % c ur cu m in , 6 % ot he r c ur cu m in oi ds 4  da ys 18 0  m g 90  m g tw ic e a da y at br ea kf as t a nd d in ne r, co ns um ed fo r 4  d ay s af te r e xe rc is e A m al ra j e t a l., 2 02 0 [2 0] Tr ai ne d D ow nh ill ru nn in g fo r 45  m in C ur ei t N ot d efi ne d 4  da ys 50 0  m g/ da y C on su m ed o n da y 2, 3 an d 4 of st ud y N ic ol e t a l., 2 01 5 [2 1] Tr ai ne d 7 se ts o f 1 0 ec ce nt ric si ng le -le g pr es s re pe tit io ns o n a le g pr es s m ac hi ne Eu ro fin s s ci en tifi c In c N ot d efi ne d 5  da ys 50 00  m g/ da y 5 ca ps ul es (2 .5  g c ur - cu m in ) t w ic e da ily fo r 2 .5  d ay s p rio r to e xe rc is e, th en 5 ca ps ul es tw ic e da ily fo r 2 .5  d ay s a fte r ex er ci se M us cl e pe rfo rm an ce Ta na be e t a l., 2 01 8 [2 2] U nt ra in ed 30 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity o f 12 0° /s Th er ac ur m in N ot d efi ne d 7  da ys 18 0  m g 90  m g tw ic e a da y at br ea kf as t a nd d in ne r, co ns um ed fo r 7  d ay s af te r e xe rc is e Ta na be e t a l., 2 01 9 [2 3] U nt ra in ed 30 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity o f 12 0° /s Th er ac ur m in 30 % c ur cu m in , 6 % ot he r c ur cu m in oi ds 4  da ys 18 0  m g 90  m g tw ic e a da y at br ea kf as t a nd d in ne r, co ns um ed fo r 4  d ay s af te r e xe rc is e Ta na be e t a l., 2 01 5 [5 3] U nt ra in ed 50 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity 12 0° /s Th er ac ur m in N ot d efi ne d Si ng le d os e 30 0  m g 15 0  m g 1  h be fo re ex er ci se a nd 1 50  m g 12  h a fte r e xe rc is e 3851European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 5 (c on tin ue d) EI M D m ar ke rs a nd ox id at iv e m ar ke rs A ut ho r Tr ai ni ng st at us o f pa rti ci pa nt s Ex er ci se p ro to co l Fo rm ul at io n C ur cu m in oi ds co nt en t D ur at io n D os ag e Ti m in g of d os e C re at in e ki na se N ak ho sti n- Ro oh i et  a l., 2 01 6 [1 9] U nt ra in ed U na cc us to m ed sq ua t ex er ci se s Th er ac ur m in 10 % c ur cu m in , 2 % cu rc um in oi ds w ith - ou t c ur cu m in Si ng le d os e 15 0  m g Im m ed ia te ly p os t- ex er ci se Ta na be e t a l., 2 01 8 [2 2] U nt ra in ed 30 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity o f 12 0° /s Th er ac ur m in N ot d efi ne d 7  da ys 18 0  m g 90  m g tw ic e a da y at br ea kf as t a nd d in ne r, co ns um ed fo r 7  d ay s af te r e xe rc is e M cF ar lin e t a l., 2 01 6 [2 4] U nt ra in ed 6 se ts o f 1 0 re p- et iti on s o f t he le g pr es s e xe rc is e w ith a be gi nn in g lo ad se t a t 1 10 % o f t he ir es tim at ed 1 R M Lo ng vi da N ot d efi ne d 6  da ys 40 0  m g 48  h b ef or e ex er ci se an d fo r 7 2  h af te r Ta na be e t a l., 2 01 5 [5 3] U nt ra in ed 50 m ax im al e cc en tri c co nt ra ct io ns o f t he el bo w fl ex or s a t a n an gu la r v el oc ity 12 0° /s Th er ac ur m in N ot d efi ne d Si ng le d os e 30 0  m g 15 0  m g 1  h be fo re ex er ci se a nd 1 50  m g 12  h a fte r e xe rc is e S. B as ha m e t a l., 20 19 [2 6] Tr ai ne d 22 5 re pe tit io ns o f s it an d st an d us in g an ae ro bi c ste p be nc h in 1 5  m in C ur cu Fr es h 69  m g of c ur cu m i- no id s 28  d ay s 15 00  m g/ da y 10 00  m g at b re ak fa st an d 50 0  m g at d in ne r N ic ol e t a l., 2 01 5 [2 1] Tr ai ne d 7 se ts o f 1 0 ec ce nt ric si ng le -le g pr es s re pe tit io ns o n a le g pr es s m ac hi ne Eu ro fin s s ci en tifi c In c N ot d efi ne d 5  da ys 50 00  m g/ da y 5 ca ps ul es (2 .5  g c ur - cu m in ) t w ic e da ily fo r 2 .5  d ay s p rio r to e xe rc is e, th en 5 ca ps ul es tw ic e da ily fo r 2 .5  d ay s a fte r ex er ci se Tu m ou r n ec ro si s fa ct or -α M cF ar lin e t a l., 2 01 6 [2 4] U nt ra in ed 6 se ts o f 1 0 re p- et iti on s o f t he le g pr es s e xe rc is e w ith a be gi nn in g lo ad se t a t 1 10 % o f t he ir es tim at ed 1 R M Lo ng vi da N ot d efi ne d 6  da ys 40 0  m g 48  h b ef or e ex er ci se an d fo r 7 2  h af te r 3852 European Journal of Nutrition (2022) 61:3835–3855 1 3 Ta bl e 5 (c on tin ue d) EI M D m ar ke rs a nd ox id at iv e m ar ke rs A ut ho r Tr ai ni ng st at us o f pa rti ci pa nt s Ex er ci se p ro to co l Fo rm ul at io n C ur cu m in oi ds co nt en t D ur at io n D os ag e Ti m in g of d os e In te rle uk in -6 N ic ol e t a l., 2 01 5 [2 1] Tr ai ne d 7 se ts o f 1 0 ec ce nt ric si ng le -le g pr es s re pe tit io ns o n a le g pr es s m ac hi ne Eu ro fin s s ci en tifi c In c N ot d efi ne d 5  da ys 50 00  m g/ da y 5 ca ps ul es (2 .5  g c ur - cu m in ) t w ic e da ily fo r 2 .5  d ay s p rio r to e xe rc is e, th en 5 ca ps ul es tw ic e da ily fo r 2 .5  d ay s a fte r ex er ci se In te rle uk in -8 M cF ar lin e t a l., 2 01 6 [2 4] U nt ra in ed 6 se ts o f 1 0 re p- et iti on s o f t he le g pr es s e xe rc is e w ith a be gi nn in g lo ad se t a t 1 10 % o f t he ir es tim at ed 1 R M Lo ng vi da N ot d efi ne d 6  da ys 40 0  m g 48  h b ef or e ex er ci se an d fo r 7 2  h af te r F. D ro bn ic e t a l., 20 14 [7 0] Tr ai ne d M od ifi ed d ow nh ill ru nn in g te st— ru n- ni ng a t a c on st an t sp ee d fo r 4 5  m in af te r a 1 0- m in w ar m -u p on tr ea d- m ill M er iv a® 20 0  m g/ do se 4  da ys 1  g tw ic e a da y 48  h p rio r t o ex er ci se an d co nt in ue d fo r 24  h a fte r e xe rc is e B io lo gi ca l a nt io xi - da nt p ot en tia l a nd gl ut at hi on e Ta ka ha sh i e t a l., 20 13 [2 5] Re cr ea tio na lly a ct iv e W al ki ng o r r un ni ng at 6 5% V ̇O 2 m ax on a tr ea dm ill fo r 60  m in Th er ac ur m in 10 % c ur cu m in , 2 % cu rc um in oi ds w ith - ou t c ur cu m in 1  da y 18 0  m g/ da y 2  h be fo re a nd im m e- di at el y af te r e xe rc is e 3853European Journal of Nutrition (2022) 61:3835–3855 1 3 Funding Open Access funding enabled and organized by CAUL and its Member Institutions. No sources of funding were used to assist in the preparation of this article. Availability of data and materials Not applicable. Code availability Not applicable. Declarations Conflict of interest Krutika Nanavati, Ajmol Ali, Kay Rutherfurd- Markwick, Sung Je Lee and Nicolette Bishop declare that they have no conflicts of interest relevant to the content of this review. Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Open Access This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. 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