Rhodiola rosea as an adaptogen to enhance exercise ...

Rhodiola rosea (RR) is a plant whose bioactive components may function as adaptogens, thereby increasing resistance to stress and improving overall resilience. Some of these effects may influence exercise performance and adaptations. Based on studies of rodents, potential mechanisms for the ergogenic effects of RR include modulation of energy substrate stores and use, reductions in fatigue and muscle damage and altered antioxidant activity. At least sixteen investigations in humans have explored the potential ergogenicity of RR. These studies indicate acute RR supplementation (&#;200 mg RR containing &#;1 % salidroside and &#;3 % rosavin, provided 60 min before exercise) may prolong time-to-exhaustion and improve time trial performance in recreationally active males and females, with limited documented benefits of chronic supplementation. Recent trials providing higher doses (&#; to mg RR/d for 4&#;30 d) have demonstrated ergogenic effects during sprints on bicycle ergometers and resistance training in trained and untrained adults. The effects of RR on muscle damage, inflammation, energy system modulation, antioxidant activity and perceived exertion are presently equivocal. Collectively, it appears that adequately dosed RR enhances dimensions of exercise performance and related outcomes for select tasks. However, the current literature does not unanimously show that RR is ergogenic. Variability in supplementation dose and duration, concentration of bioactive compounds, participant characteristics, exercise tests and statistical considerations may help explain these disparate findings. Future research should build on the longstanding use of RR and contemporary clinical trials to establish the conditions in which supplementation facilitates exercise performance and adaptations.

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The longstanding medicinal use of RR and the marked popularity of dietary supplements containing extracts of this plant ( 4 ) warrant cohesive summaries of research detailing its physiological effects. While RR has been widely studied for aiding mental health and cognitive function ( 11 ) , as well as general stress and fatigue resistance ( 10 ) , the purpose of this narrative review is to describe the potential roles of RR as an adaptogen within the context of physical performance. We begin by considering preclinical research on RR&#;s putative mechanisms of action and then summarise the available clinical research on the efficacy of RR supplementation.

Rhodiola rosea (RR) is a flowering perennial plant found in Arctic regions of Europe, Asia and North America. Known by several other names &#; including roseroot, rosenroot, golden root, arctic root and more &#; this member of the Crassulaceae family has been used for medicinal purposes for centuries, with the Greek physician Dioscorides describing medicinal application in 77 AD ( 1 , 2 ) . The physiological effects of RR ingestion are thought to arise from its roles as an adaptogen, a term historically applied to substances that cause &#;a state of non-specifically increased resistance to stress&#; ( 3 ) . Adaptogens can be defined as substances that promote physiological resilience, resistance to stress and maintenance or restoration of physiological function when homoeostasis is challenged. In this regard, adaptogens may enhance physical and cognitive performance under duress, as well as general well-being, and several purported adaptogens are experiencing increased popularity in the dietary supplement industry ( 4 ) . The adaptogenic actions of RR are primarily attributed to bioactive compounds within the root, with salidroside and rosavin often noted as the most influential compounds ( 5 ) . As a result, many commercial RR preparations are standardised to specific concentrations of salidroside and rosavin. However, at least 109 chemical compounds have been identified in RR ( 2 ) . Collectively, these bioactive components have been observed to exert anti-stress and anti-fatigue effects, as well as enhance aspects of cognitive and physical performance, in part through their antioxidant properties ( 6 , 7 , 8 , 9 ) . The effects of RR on cognitive and physical function could also relate to interactions with components of physiological stress-response systems, such as monoamine neurotransmitters (e.g. serotonin and catecholamines) and opioid peptides (e.g. β-endorphins) ( 10 ) .

Compared with endurance-based exercise models, there has been less research on the potential mechanisms by which RR modifies responses to resistance training. Roumanille et al. ( 22 ) studied both acute and chronic effects of RR supplementation (2 % rosavin, 1 % salidroside) in rats performing climbing resistance exercise. The authors observed no effects of supplementation on post-exercise skeletal muscle protein synthesis. In keeping with this finding, RR had no influence on muscle growth, strength or power following 4 weeks of exercise training plus supplementation. Clearly, additional mechanistic research is needed to establish any influences of RR on adaptations to resistance training. While yet to be demonstrated in a preclinical model of resistance training, one might speculate that the aforementioned RR-induced reductions in exercise-induced muscle damage and improvements in cellular bioenergetics could positively affect resistance training.

Additional research has assessed the potential roles of RR as an antioxidant, which may be relevant to exercise training, recovery and adaptation. While reactive oxygen species have important signalling roles that affect physiological adaptations to exercise, the antioxidant status of individuals influences whether antioxidant supplementation will have positive, negative or null effects on exercise performance and adaptations ( 18 ) . As such, potential antioxidant effects of bioactive compounds should be considered alongside baseline antioxidant status, which is influenced by dietary intake, adaptations to exercise and numerous other factors. In a rodent model, Huang et al. ( 19 ) demonstrated the free radical-scavenging activity of several of RR&#;s bioactive phytochemicals (e.g. salidroside, rosavin, rosin and rosarin) and found RR supplementation enhanced weight-loaded swimming performance. In this study, 4 weeks of RR supplementation increased liver expression of the antioxidant enzymes catalase, manganese superoxide dismutase and copper/zinc superoxide dismutase; suppressed exercise-induced increases in oxygen-free radicals in blood, liver and skeletal muscle and reduced levels of the lipid peroxidation product malondialdehyde ( 19 ) . Other work has highlighted the potential of isolated salidroside to increase antioxidant enzyme activity, bolster liver glycogen and improve exercise performance following 4 weeks of supplementation ( 20 ) . Collectively, murine research that has assessed antioxidant activity alongside exercise performance has generally reported that ergogenic effects of RR supplementation are concurrent with augmented antioxidant defence systems. In these studies, RR&#;s antioxidant activity appears not to hinder beneficial exercise adaptations due to suppression of signalling by reactive species, as has been reported for certain other antioxidant supplements, such as high doses of vitamins C and E ( mg/d vitamin C and 400 mg/d vitamin E) ( 21 ) . It is also possible that the other advantageous effects of supplementation may outweigh any detrimental effects resulting from acutely increased antioxidant activity. Additionally, it is plausible that the antioxidant status of the animals used in this research may have been conducive to demonstrating ergogenic effects of a supplement with antioxidant activity ( 18 ) .

Multiple mechanisms have been proposed to explain the potential ergogenic effects of RR on exercise performance, recovery and long-term adaptations to exercise training. Several rodent studies that have demonstrated improvements in exercise performance following supplementation have probed the means by which RR acts ( 12 , 13 ) . Four weeks of RR ingestion (5&#;125 mg/d) increased resting liver glycogen content and attenuated muscle glycogen depletion during 90-min unloaded swimming exercise in Wistar rats, although the mechanism for these findings was not established ( 12 ) . RR prolonged time-to-exhaustion (TTE) during weight-loaded swimming by 21&#;65 %, with increasing doses providing greater benefits. Compared with the control group, RR supplementation reduced post-exercise fatigue biomarkers, including glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and lactate dehydrogenase, and supplementation increased skeletal muscle and liver tissue oxygenation and expression of proteins involved in TAG synthesis (sterol regulatory element-binding protein-1 and fatty acid synthase) ( 12 ) . Other work has corroborated the reduction in post-exercise lactate dehydrogenase following 30 d of RR supplementation and also finding reductions in creatine kinase, suggesting an attenuation of exercise-induced muscle damage during strenuous activity ( 14 ) . A separate investigation reported that 6 d of supplementation with 50 mg/kg/d of RR (3 % rosavin, 0·9 % salidroside) administered 30 min prior to daily exercise sessions increased swimming TTE by 25 % in Sprague-Dawley rats ( 13 ) . Mitochondrial ATP content, as estimated by a bioluminescence assay quantifying ATP reactivity with recombinant firefly luciferase ( 15 ) , was better preserved following exercise in the supplemented group, implying RR may improve mitochondrial ATP synthesis during or after intense exercise. In rat skeletal muscle cells, isolated salidroside has been found to activate AMP-activated protein kinase ( 16 ) , a master regulator of exercise signalling pathways that senses cellular energy status and exerts numerous downstream effects on carbohydrate and lipid metabolism at times of energy stress ( 17 ) . Together, these studies show that RR supplementation may enhance endurance exercise performance in rodents by countering fatigue associated with changes in cellular bioenergetics.

Studies of humans

Study characteristics

Literature search

Over the past two decades, more than a dozen clinical trials have examined the effects of RR on exercise performance and adaptations ( )(23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39). To ensure this narrative review accurately represents the current body of scientific evidence, searches were performed using several electronic databases (PubMed®, Web of ScienceTM and Scopus), with screening of relevant articles to identify research reporting the effects of RR on exercise performance and related outcomes in humans. We only considered trials providing RR in isolation, excluding those providing it as a component of a multi-ingredient supplement. In this process, we identified sixteen trials, primarily randomised controlled trials, published between and , collectively totalling 363 total participants.

Table 1.

ReferenceParticipantsStudy characteristicsResultsYearResearchers n (sex)Age (years)BM (kg)BMI (kg/m2)Training statusDesignAcute/chronic* Supplement duration (d) RR dose (mg/d)%Salidroside; %RosavinExercise testingExercise performanceOther outcomesSpasov et al.(23) 40 (M)17&#;19NRNRNRRandomised, double-blind, placebo-controlled parallel-arm trialChronic
(as SHR-5)&#;2 %
&#;3 %Bicycle ergometer
(physical work capacity-170 test)&#; Physical working capacity
&#; HR&#; Movement accuracy and speed
&#; Tapping test
&#; Mental capacity
&#; General well-being
&#; Mental fatigueAbidov et al.(24) 36 (NR)21&#;24NRNRUntrainedRandomised, double-blind, placebo-controlled parallel-arm trialChronicNR; 60 mg total active substancesBicycle ergometer
(incremental max test)NR&#;CRP
&#;CKDe Bock et al.(25) 24
(12 M, 12 F)M: 22
F: 200·3
0·3M: 72·3
F: 59·42·4
1·5NRActiveAcute: Randomised, double-blind, placebo-controlled, crossover trial
Chronic: Randomised, double-blind, placebo-controlled, parallel-arm trialsAcute & Chronic1 to 2 (Acute)
28 (Chronic)200
60-min pre-exercise1 %
3 %Bicycle ergometer
(incremental max test)
Isokinetic dynamometer
Plate-tapping test&#;TTE (acute)
&#;VO2peak
&#; Maximal isometric torque
&#; Limb movement speed&#; Sustained attentionWalker et al.(26) 12 (M)29·94·589·612·1NRTrained
(>6 months RT)Double-blind, placebo-controlled, crossover trialAcute for 3 d
on day of testNR
3 %Incremental forearm wrist flexion (to exhaustion)&#; TTE
&#; RPE&#; [PCr]
&#; [ATP]
&#; [Pi]
&#; [pH]Skarpanska-Stejnborn et al.(27) 22 (M)RR: 20·4
PL: 21·01·20·9RR: 78·6
PL: 83·310·6
7·9NRTrained
(members of national rowing team)Randomised, double-blind, placebo-controlled parallel-arm trialChronicNRRowing ergometer
( m max test)&#; Power output
&#; Exercise time&#; SOD
&#; GPx
&#; TBARS
&#; CK
&#;TAC
&#; Lactate
&#; Uric acidParisi et al.(28) 14 (M)·49·422·22·4Athletes involved in competitive sport
(8·4 ± 1·4 h training/week)Double-blind, placebo-controlled, crossover trialChronicNRBicycle ergometer
(cycle to exhaustion at 75 % VO2max)&#; VO2max
&#; HR
&#; RPE
&#; TTE&#;NEFA
&#;lactate
&#;CK
&#; for all othersNoreen et al.(29) 18 (F)22·03·356·66·2NRRecreationally activeRandomised, double-blind, placebo-controlled, crossover trialAcute1&#;170 (3 mg/kg)
60-min pre-exercise1 %
3 %Bicycle ergometer
(6-mile time trial)&#; Time to completion
&#; Average power
&#; Average cadence
&#; HR (warm-up only)
&#; RPE&#; Lactate (blood)
&#; Cortisol (saliva)
&#; Alpha amylase (saliva)
&#; Profile of Mood States
&#; Stroop Colour TestDuncan et al.(30) 10 (M)26··76·3NRRecreationally active
(3&#;10 h physical activity/week)Randomised, double-blind, placebo-controlled, crossover trialAcute1&#;203 (3 mg/kg)
60-min pre-exerciseNRBicycle ergometer
(30-min at 70 % VO2max)&#; EE
&#; Substrate oxidation
&#; HR
&#; RPE&#; Arousal
&#; Pleasure
&#; Vigour
Shanely et al.(31)
Ahmed et al.(32) 48
(35 M, 13 F)RR: 40·3
PL: 43·91·4
1·2RR: 72·7
PL: 71·02·6
2·0RR: 23·4
PL: 23·30·6
0·4Trained
(runners)Randomised, double-blind, placebo-controlled parallel-arm trialChronic·4 %
3·8 %Running
(marathon race)&#; Race performance
&#; Vertical jump
&#; DOMS&#; Viral susceptibility
&#; Virus replication
&#; Antibacterial activity
&#; Myoglobin
&#; CK
&#; AST
&#; ALT
&#; IL-6, IL-8, IL-10
&#; MCP-1
&#; G-CSF
&#; CRP
&#; eHSPDuncan et al.(33) 12 (M)24·66·0NRNRRecreationally active (3 to 10 h/week of recreational physical activity)Randomised, double-blind, placebo-controlled crossover trialAcute13 mg/kg 60-min pre-exercise1 %
3 %Treadmill (5-km time trial run at 1 % gradient)&#; Time to completion
&#; HR
&#; Blood pressure
&#; RPE&#;LactateTimpmann et al.(34) 20 (M)22·12·8RR: 76·4
PL: 83·712·2
7·8NRActiveDouble-blind, placebo-controlled parallel-arm trialChronic·3 %
2·7 %Treadmill (walk to exhaustion at 6 km/h). Conducted in climate chamber (42°C, 18 % humidity).&#;TTE
&#;HR
&#;RPE&#;Core temperature
&#;Skin temperature
&#;Cortisol
&#;Lactate
&#;GlucoseJówko et al. (35) 26 (M)RR: 20·5
PL: 20·90·3
0·2RR: 79·1
PL: 81·12·8
3·0NRRecreationally activeRandomised, double-blind, placebo-controlled parallel-arm trialChronic for 27 d
200 additional 90-min pre-exerciseNR
3 %Bicycle ergometer
(TTE/VO2peak incremental max test)&#; VO2peak
&#; TTE
&#; Maximum power
&#; Change in maximum power
&#; HR&#; Reaction time
&#; Cortisol
&#; Testosterone
&#; GH
&#; CK
&#; TAC
&#; SOD
&#; Lipid hydroperoxides
&#; Lactate (at rest)Ballmann et al.(36) 11 (F)19·40·866·28·523·32·5Active
(>150 min/week)Randomised, double-blind, placebo-controlled, crossover trialAcute for 3 d
500 additional 30-min pre-exercise1 %
3 %Bicycle ergometer
(3 × 15-s Wingate anaerobic tests)&#; Mean power
&#; Mean anaerobic capacity
&#; Mean anaerobic power
&#; Mean peak power
&#;Mean total work
&#; Mean fatigue indexN/ALin et al.(37) 12 (M)24·70·572·12·4NRActiveRandomised, double-blind, placebo-controlled, crossover trialChronicNRTreadmill
(30-min run at 75 % VO2max)NR&#; CK (72 h post-exercise only)
&#; Lactate
&#; IL-1B
&#; IL-6
&#; TNF-α
&#; CRPWilliams et al.(38) 10 (M)24·85·683·27·6NRResistance-trained
(8·7 ± 6·3 years experience)Randomised, double-blind, placebo-controlled, crossover trialAcute for 3 d
500 additional 30-min pre-exercise1 %
3 %Resistance exercise
(bench press)&#; Mean concentric velocity
&#; Total repetitions (RTF)&#; Lactate
&#; Epinephrine
&#; NorepinephrineLiu et al.(39) 48 (M)20·52·675·17·024·41·7UntrainedRandomised, double-blind, placebo-controlled, crossover trialChronic·5 %
NRResistance exercise
(squat and bench press)&#; 1RM (bench press)
&#; 1RM (squat)
&#; MVIC (knee extension)
&#; RTF (bench press)N/AOpen in a separate window

Exercise protocols

Eight of the clinical studies identified included bicycle ergometry as an exercise testing modality, and the specific protocols varied widely(23,24,25,28,29,30,35,36). Three trials included running, either on a treadmill(33,37) or as a marathon race(31,32), one trial employed walking on a treadmill in a climate chamber(34), one trial used rowing ergometry(27) and three trials incorporated resistance exercise, including wrist flexion(26), bench press(38,39) and/or squat exercises(39).

Participant demographics

The participants in most trials were healthy young adults, with mean ages <30 years in all trials except one, which contained participants with mean ages of &#;40 to 44 years and was described in two articles(31,32). Eleven studies included only male participants, two only included female participants, two included both sexes and biological sex was not reported in one investigation. Training status ranged from untrained to highly trained, although some descriptions of training status were vague, precluding the ability to determine the true training status of participants. Nonetheless, training statuses were designated by study authors as untrained (n 2), recreationally active (n 4), active (n 4) and trained/athletes (n 5), with training status not reported in one investigation. Collectively, based on a recent Participation Classification Framework(40), most participants likely fell within the tier 1 (recreationally active) or tier 2 (trained/developmental) categories, with the possibility of some untrained participants falling within tier 0 (sedentary)(24,39) and some highly trained participants belonging to tier 3 (highly trained/national level)(27). Six studies used acute RR supplementation protocols(26,29,30,33,36,38), defined here as 1&#;7 d of supplementation, nine implemented chronic supplementation (>7 d; range 8&#;38 d)(23,24,27,28,31,32,34,37,39) and one incorporated both acute and chronic supplementation strategies(25). Daily doses of RR ranged from 100 to mg/d. While not all studies reported the concentration of bioactive compounds, the most commonly reported concentrations were &#;1 % salidroside and &#;3 % rosavin.

Endurance exercise capacity and performance

Several trials included in this review assessed the effects of RR on endurance exercise performance. One crossover study of &#;physically active&#; males and females reported 2·4 % longer cycling TTE following acute RR ingestion(25), and a separate parallel-arm trial of male physical education students &#;not engaged in high-performance sports&#; at the time of testing found a similar increase in cycling TTE of 2·6 %, although this was not statistically significant(35). Both studies provided a 200 mg dose of RR (3 % rosavin) 60&#;90 min before the incremental maximum effort TTE test. However, one trial evaluated TTE both after acute (2-d) and chronic (28-d) supplementation(25), whereas the other only tested TTE after chronic (28-d) supplementation(35). In the study of De Bock et al.(25), an increase in TTE (+24 s, on average; RR 17·2 (se 0·8) min v. placebo 16·8 (se 0·7) min) was only observed in the acute crossover trial, and there were no between-condition differences in the subsequent parallel-arm trial included in the same report, which included 200 mg/d RR supplementation over 4 weeks. This could be due to the larger sample size per condition/group and greater statistical power in the acute trial (n 24, crossover design) compared with the chronic trial (n 11&#;12 per group, parallel arm). Similarly, the trial of Jówko et al.(35) used chronic supplementation (600 mg/d, with 200 mg/d provided before TTE tests) in a parallel-arm design (n 13 per group) and found no statistically significant effects of chronic supplementation on TTE. However, the mean difference in TTE in the RR group was +20·8 s (+2·6 %) after 4 weeks of supplementation compared with &#;10·1 s (-1·3 %) with placebo. As such, it is possible these trials of chronic supplementation were underpowered to detect a small-but-meaningful influence of supplementation on TTE performance. Additionally, analysis of changes in maximal cycling power from the incremental maximum effort TTE tests indicated a significant difference between RR (+5·7 %) and placebo (-4·1 %)(35).

Other studies have yielded conflicting or null results. In a crossover study including recreationally active females, RR improved time trial performance in a 6-mile bicycle ergometry test (RR 25·4 (se 2·7) min, placebo 25·8 (se 3·0) min, P = 0·04) following acute supplementation with 3 mg/kg (&#;170 mg) RR provided 60 min before exercise(29). RR also reduced average heart rate during the warm-up period (RR 136 (se 17) bpm, placebo 140 (se 17) bpm). In contrast, supplementation did not affect -m rowing time in male rowers(27) or marathon performance in male and female runners(31,32). Additional research reported no benefit of acute RR supplementation for 5-km run time trial performance in recreationally active males(33), nor any benefit of chronic supplementation for a treadmill walk to exhaustion conducted in a climate chamber(34). However, a separate trial found RR decreased heart rate during bicycle ergometry work capacity testing following 20 d of supplementation with 100 mg/d(23). These findings are discordant with other investigations reporting no influence of RR on heart rate during exercise(28,30,33,34,35). The divergent training statuses, exercise testing modalities and RR dosing protocols may contribute to differences in endurance exercise performance outcomes.

As discussed, improvements in TTE with RR supplementation in murine models have been associated with higher resting liver glycogen content and attenuated exercise-induced reductions in muscle glycogen(12), suggesting that alterations in glycogen turnover potentially contribute to ergogenic effects on endurance exercise following chronic supplementation. RR has also been found to support mitochondrial ATP content(13), representing another mechanism by which RR may improve prolonged exercise performance. However, similar outcomes have not been examined in human participants to determine whether these mechanisms contribute to the observed results.

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Power and resistance exercise performance

Although limited, clinical research examining the effects of RR supplementation on power and resistance exercise performance has demonstrated potentially meaningful ergogenic effects. In their study of physically active (>150 min/week of moderate physical activity) young adult females, Ballmann et al.(36) observed improvements in nearly all outcomes during repeated Wingate tests (3 × 15-s tests) performed on a bicycle ergometer, including mean and peak power, total work, anaerobic capacity and anaerobic power following RR supplementation. Effect sizes indicating the magnitude of performance improvements ranged from small to large, with the largest values observed for anaerobic capacity (RR 10·5 (se 0·9) watts/kg body mass, placebo 10·1 (se 1·1) watts/kg; P = 0·01; Cohen&#;s d effect size 0·96 (large)) and anaerobic power (RR 15·2 (se 1·1) watts/kg body mass, placebo 14·0 (se 1·2) watts/kg; P = 0·03; Cohen&#;s d effect size 1·07 (large)). The supplementation protocol included 3 d of mg/d RR (1 % salidroside, 3 % rosavin), followed by 500 mg ingestion on the fourth day, 30 min prior to exercise testing. This trial, along with a subsequent trial from the same research group(38), used a higher dose of RR than nearly all other trials we identified ( ). The origin of this higher dose appears to be a study conducted by Walker et al.(26), who sought to employ a dose higher than manufacturer recommendations in an attempt to approach doses shown to exert beneficial effects on mitochondrial ATP content in rodents(13). While one other investigation used a higher total dose of RR ( mg/d), the lower concentration of bioactive compounds (0·5 % salidroside, rosavin not reported)(39) led to a lower absolute dose of these compounds compared with the aforementioned studies. The trial of Walker et al.(26) first administered a daily dose of mg/d (3 % rosavin, salidroside not reported), although this was in the context of a muscular endurance test (incremental forearm wrist flexion to exhaustion). In this instance, there were no benefits of acute (4-d) supplementation, although the forearm exercise protocol is dissimilar to those employing multiple larger muscle groups and inducing greater systemic stress and fatigue. As discussed, other research also supports potential benefits of RR for improving maximal cycling power(35).

Two recent trials have examined whether RR supplementation improves resistance exercise performance, with one employing acute supplementation prior to exercise testing(38) and the other pairing chronic supplementation with supervised resistance training(39). In untrained participants, Liu et al.(39) found that 30 d of supplementation with mg/d RR (0·5 % salidroside, rosavin not reported) alongside supervised resistance training produced superior performance adaptations compared with placebo. The resistance training programme contained thirteen training sessions over the 30-d study and included the bench press and deep squat exercises, with 4 sets of 10 repetitions at 60 % of the pre-training 1-repetition maximum (1RM) for the first 15 d and 4 sets of 8 repetitions at 70 % of the pre-training 1RM for the last 15 d. In the RR group, greater increases were observed for bench press 1RM (9 % greater increase with RR compared with placebo; P = 0·01), squat 1RM (7·5 % greater increase with RR compared with placebo; P = 0·01), knee extension maximal voluntary isometric contraction (8·6 % greater increase with RR compared with placebo; P = 0·008) and bench press repetitions to failure (12·7 % greater increase with RR than placebo; P = 0·005). The same study also found potentially additive effects of RR and caffeine ingestion in untrained participants, leading to a follow-up examination of RR plus caffeine in resistance-trained participants. This subsequent work also found improvements in select resistance exercise performance metrics compared with placebo(39). Interestingly, Williams et al.(38) observed some beneficial and some disadvantageous effects of acute RR supplementation ( mg/d, 1 % salidroside, 3 % rosavin) on bench press performance in resistance-trained males (8·7 (se 6·3) years resistance training experience). RR supplementation led to an &#;8 % greater increase in mean concentric velocity (P = 0·049; Cohen&#;s d effect size 0·73 (medium-to-large)) during a set of 2 repetitions at 75 % of 1RM, performed with maximal explosive intent, compared with placebo. However, in a subsequent test of repetitions to failure across 3 sets at 75 % 1RM, RR supplementation reduced total repetitions completed compared with placebo (P < 0·001; Cohen&#;s d 1·90 (large)), although the difference was small (&#;2 repetitions across 3 sets). Although the test of concentric velocity can be viewed as non-fatiguing, and a 5-min rest took place between the velocity test and subsequent repetitions to failure protocol, it is possible the superior performance in the RR condition during the concentric velocity test influenced subsequent performance during the repetitions to failure test. Nonetheless, a potential tradeoff between mean concentric velocity and total training volume should be considered, as the relative importance of these variables depends on training goals and other contextual factors.

Muscle damage and inflammation

Several trials have examined the potential influence of RR on post-exercise markers of muscle damage. While RR supplementation has been found to reduce creatine kinase concentrations at rest and following fatiguing bicycle ergometry tests(24,28) and treadmill running(37), this has not been found consistently in all studies(27,31,32,35). When untrained adults performed an incremental bicycle ergometry test to exhaustion, Abidov et al. (24) found a substantial increase in creatine kinase concentrations (&#;166 U/ml at baseline to &#; U/ml 5 h after exercise), which did not appear to be influenced by RR supplementation (30 d of 680 mg/d prior to test). However, 5 d after the test, creatine kinase fell to &#; U/ml in RR condition, whereas values remained at &#; U/ml in the placebo condition, on average, suggesting a delayed effect of RR. In the same study, RR supplementation reduced C-reactive protein both 5 h and 5 d after the exercise test. Following 30 d of supplementation with 170 mg RR/d, Parisi et al.(28) reported lower creatine kinase concentrations compared with placebo, both at rest and during exercise recovery. Most of the investigations showing no effect of RR supplementation on creatine kinase and other markers of muscle damage or inflammation have included well-trained participants, such as marathon runners(31,32) and members of a national rowing team(27). As such, it is plausible that adaptations to habitual exercise training &#; such as the neural, connective tissue and cellular factors potentially contributing to the repeated bout effect(41) &#; either minimised muscle damage or otherwise reduced the likelihood of an influence of supplementation. Additional trials have reported no changes in multiple markers of inflammation, including C-reactive protein, various IL and liver enzymes following treadmill or marathon running(31,32,37).

Energy systems

As mentioned, RR influences ATP production, energy substrate storage and signalling pathways involved in cellular energy status in rodents(12,13,16). A few clinical studies have investigated outcomes related to energy metabolism. For instance, RR supplementation has been found to increase(38), decrease(28) or exert no discernible influence(27,29,33,34,37) on post-exercise lactate concentrations compared with placebo. The sole study reporting an increase in lactate concentrations with supplementation used resistance training in resistance-trained males(38), while the only trial indicating a decrease in post-exercise lactate included cycling to exhaustion in male athletes(28). The studies reporting no influence on lactate used varying exercise modalities and participants (i.e. rowing in male rowers(27), treadmill running in active males(33,37), cycling in recreationally active females(29) and treadmill walking in active males(34)).

As mentioned, RR supplementation has been reported to improve Wingate test performance, implying potential benefits related to the energy substrates and metabolic pathways involved in rapid ATP production (i.e. ATP storage, the ATP-phosphocreatine system and anaerobic glycolysis). However, one of the most informative studies relevant to these outcomes(26) demonstrated no clear influence of RR on the phosphocreatine energy system. Specifically, there were no differences in concentrations of phosphocreatine, ATP, inorganic phosphate or pH during incremental wrist flexion performed to exhaustion in resistance-trained (> 6 months training experience) males following 4 d of RR supplementation ( mg/d for 3 d, mg on the testing day; 3 % rosavin). The authors speculated the lack of effect on muscle phosphate kinetics, in contrast to rodent research(13), could have been related to supplement dosing. Specifically, they estimated that a dose of &#; mg/d RR for humans would be needed to match the dose provided by Abidov et al.(13), who reported superior mitochondrial ATP preservation following exercise in rodents supplemented with RR. Additionally, the authors acknowledged that if RR influences central fatigue, the model of wrist flexion may not be optimal to detect ergogenic effects(26). Other relevant effects observed in murine models, such as increased glycogen storage and delayed glycogen depletion(12), have yet to be examined in humans.

Antioxidant activity

Multiple bioactive compounds within RR have antioxidant activity in rodent models(19,20). In human trials, two studies have reported an increase in total antioxidant capacity, an overall measure of plasma antioxidant activity, following 28 d of 200&#;600 mg/d RR supplementation in recreationally active or highly trained individuals(27,35). This was observed for resting (pre-exercise) values in both studies and for post-exercise values in one trial(27). The differences in exercise testing protocol (i.e. -m maximal effort rowing(27) v. incremental maximal effort bicycle ergometry test(35)) and participant training status (national rowing team members(27) v. recreationally active(35)) may have influenced the difference in post-exercise total antioxidant capacity values. Alongside the increase in total antioxidant capacity, a decrease in post-exercise erythrocyte superoxide dismutase activity was observed by Skarpanska-Stejnborn et al.(27), which the authors interpreted as an indication that RR led to more effective elimination of superoxide anions in erythrocytes. However, Jówko et al.(35), who also reported increased total antioxidant capacity at rest, found no effect of supplementation on erythrocyte superoxide dismutase activity at rest, post-exercise or 24 h after exercise. Additional research is needed to clarify the degree to which RR exerts antioxidant effects in humans. Based on the lack of investigations reporting ergolytic effects of supplementation, coupled with several trials reporting positive effects, the current evidence does not suggest that any supplementation-associated increases in antioxidant status compromise exercise performance in the short term(18). However, while ten studies employed RR supplementation lasting 8&#;38 d, most investigations have not included supervised or structured exercise training alongside supplementation. As such, the influence of long-term RR supplementation on adaptations to chronic exercise training is currently unclear. Future research should employ adequately powered parallel-arm trials to establish whether long-term RR supplementation alongside progressive exercise training influences adaptations to exercise, not only in terms of antioxidant capacity but also for exercise performance, body composition and other exercise- and health-relevant outcomes.

Other outcomes

In addition to the effects of RR on exercise performance, muscle damage, inflammation, energy systems and antioxidant activity, a few other outcomes from trials in humans are noteworthy. For instance, some research groups have documented reductions in ratings of perceived exertion following acute RR supplementation (3 mg/kg; &#;170 to 203 mg) provided 30 min prior to time trial cycling(29) or cycling with a fixed duration and intensity(30). In one of these trials, reduced ratings of perceived exertion were concurrent with increases in self-reported arousal, pleasure and vigour(30). These beneficial subjective responses are aligned with other documented effects of RR, such as its anti-stress and anti-fatigue effects(8,9). While speculative, these effects could possibly be due to the influence of bioactive compounds on monoamine neurotransmitters and opioid peptides(10). However, several other trials have reported no influence of supplementation on ratings of perceived exertion(26,28,33,34). Due to potential antidepressant properties of RR (42), the possibility of varying effects, including downstream consequences for exercise performance, based on the presence of affective disorders should be considered. Furthermore, it should be noted that RR has been widely studied for aiding mental health and cognitive function(11) and promoting resistance to general stress and fatigue(10), although the purpose of the present review is to describe the roles of RR within the context of physical performance.

Additional trials have reported beneficial effects of RR supplementation that may be relevant to sports performance, such as improvements in movement speed and accuracy, reductions in mental fatigue(23) and quicker reaction time(35). Spasov et al.(23) found that 20 d of supplementation with 100 mg/d RR (2 % salidroside, 3 % rosavin) reduced self-assessed mental fatigue, with a &#;30 % decrease in fatigue &#; based on a questionnaire evaluating various forms of fatigue, sleeping patterns, mood and mental states &#; compared with a &#;21 % increase in the placebo group. In a study of 28 d of supplementation with 600 mg/d RR (3 % rosavin), Jówko et al.(35) found significant differences in relative changes in simple reaction (median reaction time and total response time) and choice reaction (number of correct responses) with supplementation compared with placebo. Median reaction time and total response time decreased by 5·7&#;9·5 % on average with supplementation, with mean increases of &#;4 to 5 % in the placebo group. The increase in correct responses in the choice reaction test was 16 % on average with supplementation compared with an increase in 6·6 % on average with placebo. However, changes in other reaction metrics, such as median movement time during the simple reaction test and median response time in the choice reaction test, were unaffected by supplementation(35). Collectively, these findings provide initial support for benefits of RR for cognitive and subjective outcomes ancillary to exercise performance per se.

While limited data are available, one trial assessed the potential immunomodulatory actions of RR in exercising adults. After 30 d of supplementation with 600 mg/d RR or placebo, male and female runners provided serum samples before and after completing a marathon race, to examine various components of the immune system(32). While RR did not exert any obvious antibacterial effects, a decrease in viral replication following vesicular stomatitis virus was evident in the serum of runners supplementing with RR, leading the authors to conclude that supplementation could help defend against exercise-induced susceptibility to viral infections(32). If this is the case, the finding is potentially meaningful due to the detrimental impacts of acute illnesses in athletes, the inability to train and compete due to infection and the risk of infection transmission to team members(43).

3.1.1. Asthenia and Resilience

The clearest indication for R. rosea extracts&#; administration is the management of asthenic conditions, including: a decline in work performance due to physical or intellectual strain, mental and physical fatigue, sleep disturbances, poor appetite, irritability, hypertension, headaches, etc. [1,2,4]. The extract from the rhizomes of R. rosea acts as an adaptogen that aims to increase the body&#;s resistance to the imposed stressors and has a normalizing effect independent of the nature, either environmental or emotional, of the stress signal [6]. The plant&#;s dual actions of cognitive stimulation and emotional calming create benefits for both immediate cognitive and memory performance, as well as for the long-term preservation of brain functions. This is the main adaptogen given the indication &#;stress&#; by the EMA [7]. A number of clinical trials have supported these effects.

Darbinyan et al. [10] investigated the effect of the chronic administration of 170 mg of standardized R. rosea rhizome extract on aspects of mental performance and fatigue on 56 healthy male and female physicians (age 24&#;35) on night duty for 14 days. In a randomized, placebo-controlled, double-blind, cross-over study with a wash-out period, total mental performance was measured by calculating a Fatigue Index that reflected on the outcomes of complex perceptive and cognitive cerebral functions, such as associative thinking, attention capacity, speed of visual and auditory perception and short-term memory. A statistically significant improvement in the Fatigue Index was observed in the R. rosea treatment group. Additionally, the improved mental performance reverted to baseline values during the washout period, supporting the beneficial effects of the extract. Among people suffering from life-stress symptoms, R. rosea treatment over four weeks resulted in an overall therapeutic effect with clinically relevant improvements in stress symptoms, stress-related disabilities in work, social and family life and functional impairment. In this single-arm, multicenter study by Edwards et al. [11], various aspects of stress symptoms and psychological well-being were evaluated in 101 adult subjects with life-stress symptoms who received R. rosea root extract (200 mg, twice-daily). All outcome measurements showed significant, consistent and steady improvements in stress symptoms, fatigue, quality of life, mood, concentration, disability, functional impairment and an overall therapeutic effect.

In two separate studies, Spasov and colleagues investigated the effects of R. rosea on students during their final exam period [12,13]. During the first study, 40 medical students were randomized to receive either 50 mg of a standardized R. rosea extract or placebo twice daily for a period of 20 days [12]. The students receiving R. rosea demonstrated significant improvements in physical fitness, neuro-motoric functions, mental performance, and general well-being. Statistically significant reductions in mental fatigue, including improved sleep patterns and a reduced need for sleep, greater mood stability and a greater motivation to study were also reported in the treatment group. In a follow-up, double-blind, placebo-controlled study by the same group, 60 students received either 660 mg/day R. rosea extract, placebo, or nothing for 20 days [13]. The administration of R. rosea resulted in an increase in the physical work capacity, coordination, kinesthetic sensitivity, and general well-being of the students, along with a decrease in fatigue and situational anxiety.

A randomized, double-blind, placebo-controlled, parallel-group clinical study by Shevtsov et al. compared the effect of a single dose of either 370 mg or 555 mg of standardized R. rosea extract to placebo on the capacity for mental work against a background of fatigue and stress in 161 cadets aged from 19 to 21 years [14]. The study showed a pronounced anti-fatigue effect in both R. rosea treatment groups, with no significant difference between the two dosages. Additionally, the levels of stress and fatigue were measured by Schutgens et al. in a double-blind, placebo-controlled clinical trial [15]. Thirty subjects were randomly assigned to three groups: a placebo group, a group that took 144 mg of R. rosea extract, and a group that took a supplement called ADAPT-232, a fixed combination of Eleutherococcus senticosus Rupr. and Maxim., R. rosea L. and Schisandra chinensis (Turcz.) Baill. After 1 week of supplementation, a significant decrease in the experienced level of fatigue was observed in the Rhodiola group compared with the placebo and the ADAPT-232 groups.

R. rosea was shown to improve all dimensions of chronic fatigue and burnout-related symptoms. Investigating these effects of R. rosea, a non-interventional study was conducted in 128 primary care practices in Germany, including 330 patients with burnout indicator symptoms (exhaustion, depression, insomnia, fatigue or drop in performance). A considerable alleviation of these complaints after the administration of R. rosea over 8 weeks was reported, along with very good tolerability [16]. Likewise, in a double-blind, placebo-controlled clinical trial, 60 participants, selected according to the diagnostic criteria for fatigue syndrome, were randomized to receive R. rosea (576 mg extract/day) or placebo for four weeks [17]. R. rosea was found to exert a notable anti-fatigue effect that increased mental performance, particularly the ability to concentrate, and decreased cortisol response to awakening stress in burnout patients. In addition, another exploratory single-arm, multi-center study investigated the clinical outcomes of R. rosea intervention (200 mg of R. rosea extract) in 118 burnout patients [18]. The fatigue symptoms experienced by the patients continuously declined during the 8 weeks of intervention, with noteworthy results after only one week of treatment, and a statistically significant improvement at week 8. Finally, an open-label, multicenter, single-arm trial by Kasper et al. [19], explored the clinical outcomes in burnout patients treated with 400 mg of R. rosea extract over 12 weeks. A wide range of outcome measures assessed in the trial, such as alertness, calmness and good mood, clearly improved over time, with considerable changes already being detected after the first week of R. rosea administration.

The ability of R. rosea to increase the non-specific resistance and exert neuroprotective properties have been primarily attributed to its capacity to influence the levels and activity of several components of the stress-response system, including monoamine neurotransmitters such as serotonin and catecholamine, and opioid peptides such as β-endorphins [1,5,20,21,22,23,24]. In small and medium doses, R. rosea administration was found to stimulate the noradrenalin, serotonin, dopamine and acetylcholine receptors in the central nervous system (CNS) [24]. It also enhanced the effects of these neurotransmitters on the brain by increasing the permeability of the blood&#;brain barrier to precursors of dopamine and serotonin [25]. Additionally, the literature data indicate that R. rosea may stimulate the synthesis, transport, and receptor activity of opioid receptors and peptides such as the β-endorphins [23,26]. β-endorphins attenuate the intensity of the stress response and the sudden release of opioid peptides that occurs as part of the pituitary&#;adrenal axis response to stress. The excess production of endorphins at stressful situations interferes with normal brain functions and can lead to heart damage. In addition, R. rosea might protect the brain and heart by reducing the secretion of corticotrophin releasing factor (CRF) under stress, decrease corticosterone levels and increase the expression of stress-responsive genes, especially in the hippocampus and prefrontal cortex [27,28].

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