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, recovery, along with bioavailability of curcumin as follows: (“curcumin” OR “turmeric”) AND (“muscle damage” OR “delay onset muscle soreness” OR “DOMS” OR “inflammation” OR “inflammatory” OR “inflammatory markers” OR “oxidative stress”) AND (“exercise”). For articles on other natural 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 performance’’), 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, hexahydrocurcumin, and octahydrocurcumin by reductases in enterocytes and hepatocytes [40]. For phase II, both curcumin and its metabolites from phase I undergo conjugation with sulphate 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 metabolised by intestinal microbiota, such as Escherichia coli to tetrahydrocurcumin with the help of an NADPH-dependent reductase and by Blautia sp. MRG-PMF1 (anaerobic bacterial strain) that facilitates curcumin demethylation to form demethylcurcumin and bis-demethylcurcumin [46].

Fig. 1

Metabolic pathways of curcumin

Pharmacokinetics of curcumin supplements

Absorption, distribution, hepatic and intestinal metabolism, and excretion regulate the bioavailability of ingested curcumin [45]. In addition, the physicochemical properties of each curcumin formulation and the dose, along with its rate of degradation in the lumen, lipophilicity, and gastric emptying time, help determine the body’s pharmacokinetics [47].

Some studies have assessed plasma curcumin levels after hydrolysis of blood plasma samples, however, such hydrolysis prior to extraction masks the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolysed samples [50]. When treated with the enzymes β-glucuronidase and sulfatase, curcumin generates glucuronide curcumin and curcumin sulphate, which are the primary circulating forms of curcumin but are physiologically inactive conjugates. This obscures the free bioactive curcumin 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 pharmacokinetic 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) [41,42,43,44, 49, 50].

Table 1 Composition of different curcumin formulationsTable 2 Pharmacokinetic parameters of curcumin from the different curcumin-based formulations and reference (unformulated curcumin) in human studies

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 dispersion 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 curcumin formulation with Tween 80 (non-ionic surfactant and emulsifier) that could deliver most of the curcumin to the intestinal wall for absorption by escaping the phase separation 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 natural curcuminoids and lecithin (phosphatidylcholine phytosome 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 unformulated 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] incorporated 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 containing 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 parameters such as curcumin/lipid/antioxidant ratio, globule-size distribution, and stability [51].

Consumption of a combination of curcumin and piperine in the Curcumin C3 Complex + Bioperine resulted in a 20-fold increase in plasma curcumin concentrations compared to the control formulation with the lowest Tmax of 0.69 h. Piperine is a P-glycoprotein and a uridine diphosphate-glucuronosyltransferase (UGT) inhibitor, and is suggested to improve absorption of curcumin by decreasing the efflux in the intestine and increasing the freely available 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 concentration 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).

Table 3 Summary of plasma curcumin concentration in studies examining the effect of curcumin intake on exercise-induced muscle damage (EIMD)Table 4 Summary of studies examining the effect of curcumin intake on exercise-induced muscle damage (EIMD)

It is difficult to compare and evaluate the plasma curcumin 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 differences 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 concentrations 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 overestimating 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 curcumin 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 inflammatory markers such as IL-6, TNF-α, and CK, also hindering comparisons between studies [54].

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 [16,17,18]. EIMD is characterised by muscular ultrastructural 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 inflammatory 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 participants 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 definitive conclusions as to whether curcumin supplementation is effective.

Muscle soreness

EIMD leads to delayed onset muscle soreness, associated 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 influence 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 redness, swelling (due to increased membrane permeability), and pain at the site of muscle damage [28]. Curcumin downregulates the expression of COX-2 and thus, decreases the release of prostaglandins [29] which in turn reduces muscle soreness [19,20,21,22,