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Rhodiola Update

iStock-889086356Rhodiola rosea (also known as rosenroot, golden root, rose root, and arctic root) has a long history of use throughout Asia and Europe, primarily as an “adaptogen,” a botanical thought to have broad applicability for improving fatigue, physical endurance, host defenses, and resistance to the effects of stress, typically with polyvalent mechanisms of action. Several recent publications point to rhodiola’s likely mechanisms of action and clinical uses, ranging from cardiovascular support to enhancing the gains of exercise.

For example, a recent literature review and network pharmacology analysis (a computer-based approach to determine the molecular interactions of compounds within the cell) of salidroside, thought to be one of the main active components of rhodiola, suggests it has multiple targets relevant to cardiovascular function. It may inhibit the inflammatory process which drives atherosclerosis, at least in part by preventing oxidation of LDL (ox-LDL) and foam cell formation via upregulation of nuclear factor erythroid 2-related factor 2 (nrf-2), a mechanism demonstrated previously in vitro. Additionally, salidroside was shown to upregulate p-AMPK, PPAR-α and PGC-1α in an experimental model, all signals which may mitigate myocardial injury. Upregulation of PGC-1α, for example, increases mitochondrial biogenesis, protective not only against endothelial injury, but potentially with much broader implications. Unfortunately, most data related to cardiovascular disease is in the pre-clinical phase, lacking well-controlled trials.

There is more clinical data related to the enhancement of physical performance when combined with exercise. In a recent systematic review of 10 clinical trials, mostly randomized or cross-over trials, generally favorable effects were found for rhodiola supplementation. For instance, it was associated with reduced muscle damage following various types of exercise, including exhaustive exercise, in several of the included studies. It also was associated with a lower rate of perceived exertion and improved exercise endurance performance, and greater resting plasma total antioxidant capacity in two of three studies examined. In the only study examining explosive power, supplementation was associated with an increase in explosive power, but this may have been at the expense of reduced endurance. In all 10 trials included in the analysis, no adverse effects of supplementation were reported. Additionally, in a recent controlled trial not included in the systematic review, rhodiola given in combination with caffeine was shown to improve exercise performance, including maximum voluntary isometric contraction (MVIC) and deep squat one repetition maximum (1RM) in both resistance-trained and untrained volunteers, as well as bench press 1RM, and the maximum repetitions at 60% 1RM bench press in untrained volunteers. Rhodiola was given for 30 days leading up to the evaluations, while only one dose of caffeine was given on the same day.

Regarding adaptations to stress and generalized fatigue, a recent review published in Molecules indicated generally favorable effects of rhodiola supplementation. For example, one randomized and controlled clinical trial included in this review found that supplementation had an anti-fatigue effect among study participants with fatigue syndrome. This included improvements in mental performance, particularly the ability to concentrate, and decreased cortisol morning stress response. In an open-label clinical trial, study participants with fatigue had improvement after 1 week of supplementation, which continued to improve throughout the 8-week study period. A subsequent multi-center open-label trial found that participants with significant life-stress (“burnout,” assessed via several validated scales) found that a wide range of measures improved over the 12-week study period, including “emotional exhaustion” (assessed by the Maslach Burnout Inventory (MBI-D)), fatigue, mood-related symptoms (e.g., “lack of joy,” “loss of zest for life,” etc.), sexual interest and functioning, and more. In one of the few-placebo controlled trials, rhodiola supplementation at two different dosages was found to improve mood, sleep, insomnia, and emotional instability among study participants with low mood compared to placebo, assessed by the Beck Depression Inventory and Hamilton Rating Scale for Depression (HAMD) questionnaires. Certainly, well-controlled randomized and placebo-controlled trials would help to buttress these findings.

Many mechanisms of action are suggested in the review published in Molecules. This includes increased levels of serotonin, catecholamines, and β-endorphins, with experimental data suggesting that modulation of the hypothalamic-pituitary axis is also likely, including decreasing the stress-induced elevation of CRH (corticotropin-releasing hormone) and subsequent cortisol production. This provides a likely mechanism for the adrenal support role often attributed to rhodiola, as a reduction in CRH would ultimately reduce stimulation of the adrenal glands.

In a 2022 study published in Oxidative medicine and cellular longevity, an in vitro model suggested a number of additional mechanisms related to mitochondrial function and cellular stress. In these models, rhodiola was shown to counter the effects of glucocorticoid-induced stress by increasing BDNF (brain-derived neurotrophic factor) levels, ATP production, and inhibiting reactive oxygen species synthesis. This study also found that rhodiola enhanced mitochondrial biogenesis (as mentioned above), suggesting another possible mechanism for both enhancing both the resilience to stress and exercise capacity. An upregulation of PGC-1α by salidroside was also observed in an experimental model, in which salidroside provided protection against particulate matter toxicity through this and other antioxidant mechanisms. Upregulation of PGC-1α appears to be a key mediator of exercise-induced adaptations.

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