Rhodiola Rosea - Scientific Review on Usage, Dosage, Side Effects _ Examine

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Summary (All Essential Benefits/Effects/Facts & Information)

Rhodiola rosea is a herb in the rhodiola genera (Crassulaceae family)

which has traditional usage as an anti-fatigue agent and Adaptogen

(/supplements/Adaptogen/) compound, and rhodiola is likely the second

SUMMARYTHINGS TOKNOWHOW TO TAKEEDITORS'THOUGHTS

COMPLETESUMMARYCITATIONS

QuickSummary:

Rhodiola rosea is a

Traditional Chinese

Medicine (/supplements

/Traditional+Chinese+Medicine/)

and Scandinavian herb

touted to promote

physical/cognitive vitality.

It appears to be proven

for reducing fatigue and

exhaustion in prolonged

stressful situations.

Rhodiola is also

neuroprotective and

promotes longevity in

preliminary evidence.

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/Rhodiola+Rosea/) •

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Rhodiola rosea is a Traditional Chinese Medicine (/supplements/Traditional+Chinese+Medicine/) and Scandinavian herb touted topromote physical/cognitive vitality. It appears to be proven forreducing fatigue and exhaustion in prolonged stressful situations.Rhodiola is also neuroprotective and promotes longevity inpreliminary evidence.

This page features 132 unique references to scientific papers.

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HUMAN EFFECTMATRIX

Rhodiola Rosea - Scientific Review on Usage, Dosage, Side Effects | Exa... http://examine.com/supplements/Rhodiola+Rosea/

1 of 35 1/31/2014 9:31 AM

Also Known As

Rosavin, Rosenroot, Rhodiola Is a Form of

most popular adaptogen (second only to Panax ginseng (/supplements

/Panax+ginseng/)).

In regards to fatigue, rhodiola appears to be able to significantly reduce the

effects of prolonged and minor physical exhaustion that results in fatigue.

This is more related to stress and the 'burnout' effect, or prolonged but low

intensity physical exercise. There is some limited evidence that parameters

of physical exercise can be improved with rhodiola, but this appears to be

limited to untrained persons with numerous studies on trained athletes

suggesting that rhodiola does not have an acute ergogenic effect. Despite

this, rhodiola appears to be highly reliable in reducing fatigue symptoms

and improving symptoms of stress (and secondary to that, well-being) in

persons fatigued from non-exercise related stressors.

Rhodiola can improve cognitive functioning in persons who experience a

reduction in fatigue, but there is insufficient evidence to support an outright

increase in cognition (which should occur in non-fatigued persons) and not

enough studies have assessed cognitive decline for conclusions to be

made.

Other potential uses of rhodiola include preliminary evidence that it is

highly neuroprotective against toxins (requires more evidence) and that

ingestion of rhodiola or its active component can reduce stress-induced

binge eating in female rats. In the brain, rhodiola appears to be highly

serotonergic (increases serotonin) and reduces corticosteroids; the

inhibition of monoamine oxidases (MAOs) commonly attributed to rhodiola

may not be relevant following oral ingestion of rhodiola, however.

Rhodiola may also promote longevity, with preliminary (non-mammalian)

evidence suggesting up to a 20% increase in lifespan secondary to

mechanisms that are indepedent of caloric restriction. Although very

promising, mammalian evidence is needed to confirm.

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Things to Know



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





History (/history




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HUMAN EFFECTMATRIX


2 of 35 1/31/2014 9:31 AM

Rhizome, Golden Root, Arctic Root,

Rhidola

Do Not Confuse With

Other species of Rhodiola, Rosa

damascena (/supplements

/Rose+Essential+Oil/), Rosmarinic

Acid (/supplements

/Rosmarinic+Acid/), Roselle

(/supplements

/Hibiscus+sabdariffa/), Scutellaria

baicalensis (/supplements

/Scutellaria+baicalensis/) (also

called Goldenroot)

Things to Note

Rhodiola Rosea is slightly stimulatory,

although not classically stimulatory

like Caffeine (/supplements/Caffeine/)

Rhodiola rosea is known to inhibit the

CYP3A4 enzyme in vitro at

concentrations which likely occur to

oral ingestion

Stress Relief (/supplements

/Stress+Relief/)

Adaptogen (/supplements

/Adaptogen/)

Traditional Chinese Medicine

(/supplements


Goes Well With

Eleutherococcus senticosus

(/supplements

/Eleutherococcus+senticosus/)

and Schisandra chinensis

(/supplements

/Schisandra+chinensis/) (as the

blend known as ADAPT-232)

Cranberry water extract

(α-amylase and α-glucoside

inhibition)

Hypericum perforatum

(/supplements

/Hypericum+perforatum/) (binge

eating)

Stacks Part Of

Cravings (/stacks

/cravings.html)

Fatigue and Stress (Chronic)

(/stacks/fatigue-and-stress-

chronic.html)

Addiction (/stacks

/addiction.html)

Caution Notice

Rhodiola rosea may interact

with enzymes of drug

metabolism

Examine.com Medical Disclaimer ()



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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HUMAN EFFECTMATRIX


3 of 35 1/31/2014 9:31 AM

When cycling off of something like Caffeine (/supplements/Caffeine/), I foundRhodiola Rosea made it a lot easier for the body.

— Sol Orwell (/user/Sol/)

How to Take (recommended dosage, active amounts,

other details)

Supplementation of rhodiola rosea tends to refer to either the SHR-5

extract in particular or an equivalent extract, any that confers both 3%

rosavins and 1% salidroside.

Usage of rhodiola as a daily preventative against fatigue has been reported

to be effective in doses as low as 50mg.

Acute usage of rhodiola for fatigue and anti-stress has been noted to be

taken in the 288-680mg range.

As rhodiola has been shown to have a bell-curve response before, it is

recommended to not exceed the aforementioned 680mg dosage as higher

doses may be ineffective.

Editors' Thoughts on RhodiolaRosea

Human Effect Matrix



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





History (/history




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HUMAN EFFECTMATRIX


4 of 35 1/31/2014 9:31 AM

A

B

C

D

The Human Effect Matrix looks at human studies (excluding animal/petri-dishstudies) to tell you what effect Rhodiola Rosea has in your body, and how strongthese effects are.

GRADE LEVEL OF EVIDENCE

Robust research conducted with repeated double blind clinical trials

Multiple studies where at least two are double-blind and placebo

controlled

Single double blind study or multiple cohort studies

Uncontrolled or observational studies only

LEVEL OFEVIDENCE

() EFFECT

CHANGE ()

MAGNITUDEOF EFFECT

SIZE () SCIENTIFIC CONSENSUS COMMENTS

A Fatigue (/topics/Fatigue/)Notable

100%

See all 7 studies

(/show_rubric_effect.php?id=35&

effect=Fatigue&selection=all)

The decrease in

fatigue appears

to be quite

strong and

reliable, rhodiola

may be an

active control on

this parameter

B Subjective Well-Being (/topics

/Subjective+Well-Being/) Notable

100%

See all 4 studies


effect=Subjective%20Well-Being&

selection=all)

Increases in

subjective well

being and

contentment in

fatigued or

stressed

individuals

appears to be

greater than

other

supplements.



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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5 of 35 1/31/2014 9:31 AM

LEVEL OFEVIDENCE

() EFFECT

CHANGE ()

MAGNITUDEOF EFFECT


B Cognition (/topics/Cognition/)Notable

100%

See all 4 studies


effect=Cognition&selection=all)

Notably effective

assuming

fatigue is being

reduced. There

is insufficient

evidence to

evaluate

rhodiola's

effects on

cognition without

the fatigue

reduction aspect

C Depression (/topics

/Depression/) Notable

100%

See study (/show_rubric_effect.php?id=35&

effect=Depression&selection=all)

Limited

evidence, but up

to a halving of

symptoms has

been noted with

higher doses of

Rhodiola

C Stress (/topics/Stress/)Minor

0%

See 2 studies


effect=Stress&selection=all)

Might be

effective, but the

reduction in

stress (rating

scale) appears

to be less than

that seen with

fatigue

C Heart Rate (/topics

/Heart+Rate/)

100%

See 2 studies


effect=Heart%20Rate&selection=all)

No significant

influences on

heart rate found

so far

C Rate of Perceived Exertion

(/topics

/Rate+of+Perceived+Exertion/)

Minor

0%


effect=Rate%20of%20Perceived%20Exertion&

selection=all)

Possibly

effective if

confounded with

fatigue (the

antifatigue

effects may

reduce the rate

of percieved

exertion during

submaximal

exercise) but

there does not

appear to... show



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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6 of 35 1/31/2014 9:31 AM

LEVEL OFEVIDENCE

() EFFECT

CHANGE ()

MAGNITUDEOF EFFECT


C VO2 Max (/topics/VO2+Max/) 100%


effect=VO2%20Max&selection=all)

May slightly

improve oxygen

consumption

during

submaximal

exercise in

untrained

persons, but

overall the

improvement in

VO2 max does

not appear to be

highly potent or

reliable.

C Lactate Production (/topics

/Lactate+Production/) Minor

100%


effect=Lactate%20Production&selection=all)

A decrease in

lactate

production has

been noted with

rhodiola

supplementation;

practical

significance

unknown

C Lipid Peroxidation (/topics

/Lipid+Peroxidation/)

100%

See 2 studies


effect=Lipid%20Peroxidation&selection=all)

No significant

influences on

lipid peroxidation

biomarkers in

serum

C Muscle Damage (/topics

/Muscle+Damage/) Minor

100%

See 2 studies


effect=Muscle%20Damage&selection=all)

Able to reduce

circulating levels

of creatine

kinase following

exercise

C Attention (/topics/Attention/) 100%


effect=Attention&selection=all)

No significant

influences on

attention

C Reaction Time (/topics

/Reaction+Time/)

100%


effect=Reaction%20Time&selection=all)

No significant

influences on

reaction time

C Power Output (/topics

/Power+Output/)

100%


effect=Power%20Output&selection=all)

No significant

influences on

power output



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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HUMAN EFFECTMATRIX


7 of 35 1/31/2014 9:31 AM

LEVEL OFEVIDENCE

() EFFECT

CHANGE ()

MAGNITUDEOF EFFECT


C Weight (/topics/Weight/) 100%


effect=Weight&selection=all)

Unable to modify

weight over time

C Processing Accuracy (/topics

/Processing+Accuracy/) Minor

100%


effect=Processing%20Accuracy&selection=all)

Increases in

processing

accuracy are

likely secondary

to reductions in

fatigue

C C-Reactive Protein (/topics

/C-Reactive+Protein/) Minor

100%


effect=C-Reactive%20Protein&selection=all)

A decrease in

C-reactive

protein has been

noted with

rhodiola

supplementation;

practical

significance of

these results

unknown

C Blood Pressure (/topics

/Blood+Pressure/)

100%


effect=Blood%20Pressure&selection=all)

No significant

effects yet noted

on blood

pressure

C Muscle Oxygenation (/topics

/Muscle+Oxygenation/)

100%


effect=Muscle%20Oxygenation&selection=all)

No significant

effects on

oxygenation

during exercise

or simulated

altitude tests

Studies Excluded from ConsiderationConfounded with inclusion of other nutrients

Being language barrier

Disagree? Join the Rhodiola Rosea Discussion (/discussion/Rhodiola+Rosea/)

[1][2][3]

[4]



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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8 of 35 1/31/2014 9:31 AM

Complete Summary

Table of Contents:

1. Sources and Composition1.1. Sources1.2. Composition1.3. Properties1.4. SHR-5 and ADAPT-232

2. Pharmacology2.1. Intestines and Absorption2.2. Serum2.3. Metabolism2.4. Enzymatic Interactions

3. Longevity3.1. Mechanisms

4. Neurology4.1. Mechanisms4.2. Nerve Injury and Neurogenesis4.3. Memory and Cognition4.4. Neuroprotection4.5. Serotonin4.6. Fatigue and Stress4.7. Appetite4.8. Depression4.9. Anxiety4.10. Pain

5. Cardiovascular Health5.1. Cardiac Tissue5.2. Blood Cells5.3. Blood Pressure

6. Interactions with Glucose Metabolism6.1. Absorption6.2. Mechanisms6.3. Interventions

7. Inflammation and Immunology7.1. Aging

8. Physical Exercise and Performance8.1. Mechanisms8.2. Blood Oxygenation8.3. Physical Fatigue and Performance



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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9 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Sources+and+Composition)

9. Fat Mass and Obesity9.1. Mechanisms

10. Bone Mass and the Skeleton10.1. Mechanisms

11. Interactions with Oxidation11.1. Mechanisms

12. Interactions with Hormones12.1. Estrogen

13. Interactions with Organ Systems13.1. Liver

14. Interactions with Cancer14.1. Bladder14.2. Breast14.3. Stomach

15. Nutrient-Nutrient Interactions15.1. Nicotine15.2. Weikang Keli15.3. Hypericum perforatum

16. Safety and Toxicology16.1. General

1. Sources

and Composition

1.1. Sources

Rhodiola Rosea (of the family Crassulaceae; henceforth Rhodiola) is a herb

traditionally used as an Adaptogen (/supplements/Adaptogen/) compound

and is synonymous with common names such as Arctic root, Rose

root/Rosenroot, Orpin Rose, or Golden root. The adaptogenic effects

have traditionally been referred to as inducing a 'nonspecific immunity' and

normalizing effect, and traditional usage seems to be localized to around

Europe and sometimes spreading east into Asia (with usage reported in

Mongolia and Siberia ) and is commonly reported to have traditionally

been used by scandinavian Vikings to preserve physical robustness (this

may be speculative ). It has extended far enough into Asia to be

incorporated into Traditional Chinese Medicine (/supplements

/Traditional+Chinese+Medicine/) (under the name Hong Jing Tian) where

it is recommended to take 3-6g of the root daily for vitality and longevity.

Rhodiola is common to northern Europe and Russia at altitudes between

[5][6]

[5]

[5] [6]

[6]

[7]



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Rhodiola is also

neuroprotective and





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10 of 35 1/31/2014 9:31 AM

1000-5000m, and can be found on some North American coastlines. The

main commercial source of Rhodiola appears to be Mountain Altai and in

south region of foothill Altai, mainly in Ust-Kanski, Ust-Koksinski, Charishki

regions.

Rhodiola (rosea as the most common species) is a nordic/russian herb that hastraditionally been used as a vitality enhancing and physical preserving agent. Ithas also sometimes been used for cognitive decline and the connection betweencognition and physical fatigue

1.2. Composition

The root of rhodiola (main segment that is used medicinally) contains:

Tyrosol, sometimes seen as one of the main bioactives, and its glucoside known

as Salidroside (chemically p-hydroxyphenylethyl-O-ß-D-glucopyranoside and

synonymous with Rhodioloside or Rhodosin ) as the other main bioactive

The 'Rosavins' (Rosin, Rosarin, and Rosavin are the main rosavins.

Other molecules that can possible be called rosavins include rosaridin, but

this molecule is structurally different)

Viridoside (structurally Salidroside that is methylated)

Lotaustralin (Cyanogenic glycoside)

Gossypetin (as 7-O-L-rhamnopyranoside) and Rhodioflavonoside (Gossypetin

diglycoside)

Benzyl-O-β-glycopyranoside

Procyanidins built off of EGCG (from Green Tea Catechins (/supplements

/Green+Tea+Catechins/)) at up to 35% of a 70% aqueous acetone extract by

weight. Procyanidins appear to consist of up to 3.6-5.43% of the weight of the

dry root dependeing on growing conditions which places it lower than grapes

(7.8%) and sea buckthorn (8.14%) but higher than craetagus pinnatifida

(/contribute/supplements/craetagus+pinnatifida/) (2.7%).

Small phenolics including gallic acid, cinnamic acid,

β-sitosterol

The tyrosol and salidroside molecules as well as the rosavins are known as

phenylpropanoid compounds.

On a molecular basis, the main active ingredients appear to be Tyrosol and itsglucoside known as Salidroside. When consuming the root, there are otherstructurally related bioactive (the rosavins) that may play a role. Rhodiola is asurprisingly high source of procyanidins (same molecules as those in Pycnogenol(/supplements/Pycnogenol/)) built of EGCG, the catechin thought to be somewhatunique to green tea

[5]

[6]

[8]

[8]

[9]

[10][8] [8] [8][11]

[10][11]

[8]

[11]

[12]

[12]

[10]

[8][13]

[8]

[14]

[13]

[12] [12]

[11]

[10][15]



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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11 of 35 1/31/2014 9:31 AM

The clear and colorless essential oil (0.05% of the root by dry weight, it

has been reported to be lower) contains mostly:

n-Decanol (30.38% )

Gerianol (12.49% )

1,4-p-menthadien-7-ol (5.10% )

Limonene (/supplements/Limonene/) (4.91% )

α-Pinene (4.69% )

β-pinene (1.47% )

sabinene (1.45% )

β-Myrcene (2.25% )

3-Carene (2.04% )

β-Phellandrene (2.31% )

p-Cymene (2.97% )

n-Octanol (2.77% )

Linalool (2.31% )

Dodecanol (3.67% )

Cumin alcohol (2.66% )

Due to the remarkably low level of overall essential oils in rhodiola root, thesemolecules are unlikely to play a significant role in the body followingsupplementation

1.3. Properties

Isolated salidroside and tyrosol appear to be stable in solution at 2 hours at

room temperature and 30 days at either 4°C or -20°C.

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[5]

[16]



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





History (/history




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12 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Pharmacology)

1.4. SHR-5 and ADAPT-232

SHR-5 is a standardized extract of rhodiola that is used in many human

studies and is the extract used in the formulation ADAPT-232 (a

combination of rhodiola, Schisandra chinensis (/supplements

/Schisandra+chinensis/), and Eleutherococcus senticosus (/supplements

/Eleutherococcus+senticosus/)).

The SHR-5 extract is standardized for rhodioloside (4mg per 144mg

tablet) and appears to be a 70% ethanolic extract with a 4:1 drug:extract

ratio, thus 200mg of SHR-5 is claimed to be bioequivalent to 800mg of

the dry herb.

As for ADAPT-232, the 70% ethanolic extract is used in a drug:extract

concentration of 2.8:1 while schisandra chinensis and eleutherococcus

senticosus are used as a 95% ethanolic extract (fruits) and 70% ethanolic

extract (roots) respectively and in a 1.2:1 and 10.5:1 herb:drug

concentration. Adapt-232 appears to be standardized to 0.5% rosavin,

0.32% rhodioloside, 0.05% tyrosol, 0.37% schisandrin, 0.25%

γ-schisandrin, and 0.15% eleutherosides B and E.

2.

Pharmacology

2.1. Intestines and Absorption

Salidroside appears to be absorbed in the intestines via the SGLT1

transporter (which is similar to other glucoside compounds as the

glucoside is sensed by the transpoter and this has shown efficacy in

increasing absorption of Quercetin (/supplements/Quercetin/) glucosides

relative to free quercetin ) and oral ingestion of 48mg/kg does not appear

to confer any additional advantage relative to 24mg/kg (exact same serum

concentration) although 24mg/kg outperformed 12mg/kg.

The bioavailability of salidroside has been detected to be 32.1% (12mg/kg

oral intake), 98.1% (25mg/kg), and 51.97% (100mg/kg); it is not

currently known why there is inconsistencies in these results.

2.2. Serum

Following oral ingestion of salidroside in rats, the half-life of salidroside

appears to be around 40-46 minutes with a T of 25 minutes and a

C of 10.47+/-1.08µg/mL (240 minute AUC of (695.62+/-95.39µg

[17][18]

[19]

[19]

[20]

[20]

[21]

[22]

[23]

[21]

[24] [25] [16]

[21]max

max



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Rhodiola is also

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13 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Longevity)

/h/mL). Another study using oral ingestion of 100mg/kg salidroside

noted a C of 3,716.73+/-860.13ng/mL, a T of 0.30+/-0.1 hours, and a

half-life of 1.32+/-0.22 hours with an AUC of 7,724.52+/-446.62h

/ng/mL.

2.3. Metabolism

In investigating whether salidroside in isolation can increase serum

p-tyrosol, one study has failed to find such an effect following 100mg/kg

salidroside to rats, but suggested that further metabolism was possible.

2.4. Enzymatic Interactions

In vitro, rhodiola appears to inhibit the CYP3A4 enzyme with an IC in the

range of 1.7-3.1mcg/mL and has been noted to inhibit P-glycoprotein with

an IC in the range of 16.7-51.7mcg/ML. Despite the possible

influences on CYP3A4, rhodiola has been noted to not adversely interact

with Warfarin pharmacokinetics in rats.

May possibly interact with CYP3A4 and P-gp, although there is not enoughevidence to come to a conclusion

3. Longevity

3.1. Mechanisms

Rhodiola (10-25ug/mL of feed) given to nematodes (C. Elegans) for their

lifetime was able to delay aging in the whole population (extending the time

required for the first deaths to occur) and extend life to around 10-20%; this

study also noted efficacy of Eleutherococcus senticosus (/supplements

/Eleutherococcus+senticosus/) at 10-fold the concentration, suggesting

common mechanisms. Higher doses of rhodiola (50-100ug/mL) had the

opposing effect (reducing lifespan) and adding the adaptogens later in life

(50% through the lifecyle) still exerted anti-aging effects but to a lower

degree (11.7% rather than 17.8% in a particular set of experiments).

The mechanism is thought to be secondary to DAF-16 nuclear

translocation, as DAF-16 is vital for improving heat tolerance in

nematodes which was also observed following dietary intake of

rhodiola. DAF-16 translocation is generally thought to be related to

longevity and stress resistance and the effects of rhodiola on DAF-16

is thought to be related to a hormetic mimicking of stress.

A subsequent study on drosophilia using Rhodiola at 15-200mg/mL noted

[21]

max max

0–∞[16]

[16]

50

50[26]

[27]

[28]

[28]

[28]

[29]

[28]

[30][31]

[32]



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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14 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Neurology)

significant reductions in mortality (with only the higher doses reducing

fecundity) and promoted longevity in these flies by 3.2-3.5 days, which

has been replicated twice elsewhere with an enhancement of life by

24%. Longevity has also been noted to occur in yeast, and when

comparing the two fly studies the one that had a higher concentration of

salidroside and rosavins appeared to outperform the one with standard

concentrations, suggesting they are the bioactive components.

Adaptogens in general, but particularly rhodiola, appear to be involved withpromoting longevity. A bell curve has been noted in nematodes, and themechanism is thought to be from inducing nuclear translocation of DAF-16 (aresponse to stress)

4. Neurology

4.1. Mechanisms

Ex vivo, 100µg/mL of the methanolic and water extracts can inhibit MAOA

(92.5% and 84.3%) and MAOB (81.8% and 88.9%) whereas the

dichloromethane extract appears to be less potent (50.5% and 66.9%).

When looking at causative compounds, it appears Rosiridin appears to

potently inhibit MAOB (83.8+/-1.1% at 10µM) but not MAOA (16.2+/-2.3%)

whereas salidroside was weakly effective on MAOB only (35.8+/-2.5% at

10µM). This study is duplicated elsewhere, where an inhibitory effect

on acetylcholinesterase was also noted to be and attributed to

hydroquinone, rhodiolgin, and rhodioflavonoside (although IC values

were not calculated).

The influence on monoamine oxidase has been brought into question as it

has been found that oral Rhodiola ingestion failed to modify the

5-HT/5-HIAA ratio.

It has been said rhodiola also has the ability to inhibit the COMT (Catechol-

o-methyltransferase) enzyme although the evidence this is based on

does not appear to be publicly available.

Appears to have mechanisms to inhibit MAO enzymes, and appears to be potentin vitro. This may not apply following oral ingestion of rhodiola supplements.COMT interactions have been mentioned, but there does not appear to beevidence for this claim

Rhodiola has been implicated in inducing the activity of Neuropeptide Y

[7]

[33][34] [35]

[33]

[7]

[36]

[36] [37]

50

[38]

[39]



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15 of 35 1/31/2014 9:31 AM

and subsequent release of Hsp72 (seen using the mixture of ADAPT-232

as well as isolated salidroside ) via HSP1 dependent mechanisms and

ADAPT-232 appears synergistic in this regard, as the amount of salidroside

in ADAPT-323 at the EC concentration was equivalent to 5.5nM while in

isolation salidroside needed to be present at concentrations of 5µM

(5000nM). It has been hypothesized, but not established, that these

effects may underlie the stress reducing effects of rhodiola

supplementation as increases in serum Hsp72 have been seen with

ADAPT-323 in rats.

Appears to influence Neuropeptide Y activity, which then increases Hsp72 levelsvia HSP1 transcription; thought to underlie the anti-stress effects

A psychostimulatory effect has been noted to last for 4 hours or so

following oral ingestion of 2.5mg salidroside (around 250mg rhodiola)

according to one review (main article, Aksenova 1968, not detectable

online).

May have a small psychostimulatory effect

4.2. Nerve Injury and Neurogenesis

Salidroside at 5-10mg/kg (intraperitoneal injections) to rats following a

sciatic nerve injury has been noted to accelerate the rate of nerve

healing. This has been noted with other adaptogens such as Panax

Ginseng (via Ginsenoside Rg1 ) and may be related to the

anti-degenerative effects of Hsp70 on neurons.

Requires more evidence, but has mechanisms to accelerate the rate of nervehealing

Salidroside has been noted to improve neurogenesis rates in the diabetic

rat hippocampus (thought to be from reducing oxidative stress, which may

impair neurogenesis in diabetic mammals) and has been replicated with

intracerebral injections of rhodiola. In vitro, salidroside also appears to

preserve stem cell differentiation rates in the presence of streptozotocin

(diabetic toxin used in the aforemented studies) without significantly

affecting viability up to 2mM.

As a side note, it was recorded that salidroside incubation with neurons

increased the average length of cellular processes in NF150 positive cells

[17]

50

[17]

[40]

[41]

[42]

[43]

[44]

[45][46]

[47]

[48]

[47]



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16 of 35 1/31/2014 9:31 AM

suggesting that salidroside may enhance the extension of cellular

processes in differentiating cells.

Neurogenesis may be implicated with rhodiola, but most practically this appearsto be secondary to reducing oxidation in stem cells and preserving normalneurogenesis rates (with research toxins that are oxidative in nature reducingneurogenesis rates). Practical significance of the above unknown

4.3. Memory and Cognition

In rats given a passive avoidance task, rhodiola at 50-100mg/kg for 9 days

was able to enhance memory in a dose and time dependent manner in

otherwise normal and healthy rats. Not many other studies assess

cognitive enhancement in non-stressed and healthy rats, with one

suggesting efficacy with 0.10mL of a 1:1 aqueous alcoholic extract of

rhodiola and the same dose showing inefficacy elsewhere.

50-100mg/kg rhodiola is able to abolish the memory impairing effects of

scopolamine over 9 days of oral supplementation. The memory

impairing effects from β-amyloid injections has also been noted to be

abolished with 50-75mg/kg isolated salidroside and the impairments in

both neurogenesis and cognitive function seen in diabetic rats is

abolished.

Memory improvements have been noted in persons with cognitive

impairment (not pathological) given a formulation known as Vigodana

but the results are confounded with Magnesium (/supplements

/Magnesium/) and B-vitamins.

Rhodiola has outright abolished the effects of scopolamine, suggesting it is apotent anti-amnesian agent. May also improve memory slightly independent ofstress (although in practical situations, the reduction of stress and fatigue andpreservation of cognition is likely to be the most noticeable)

4.4. Neuroprotection

Salidroside has shown protective effects in neurons exposed to

hypoglycemia and serum starvation, with pretreatment of 80-320µg/mL

preserving as many neurons as the active control of adenosine

(250µg/mL), the protective effects mediated via stabilizing the mitochondria

and thought to be related to preventing the increase in ROS (reactive

oxygen species) seen in cell pretreated with rhodiola. These possibly

antioxidative effects may also extend to protection from the oxidative stress

from β-amyloid protein (reduced with salidroside at 10-100µM) and

[47]

[49]

[50] [51]

[49]

[52]

[47][48] [53]

[54]

[55]

[55]



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17 of 35 1/31/2014 9:31 AM

subsequently reduced JNK activation and apoptosis from these proteins

which has been shown to be biologically relevant at an oral intake of

50-75mg/kg in rats.

General antioxidative effects are noted with salidroside in response to

hydrogen peroxide (H O ) which has also been noted with isolated

tyrosol galactoside.

Salidroside has been noted to induce levels of the mRNA of the

antioxidative enzymes heme-oxygenase 1 (HO-1), thioredoxin, and

peroxiredoxin-I and thus enzymatic induction may underlie the protective

effects observed with salidroside.

Salidroside, and thus rhodiola, appear to have antioxidative protective effects inisolated neurons. The mechanisms appear to be from inducing levels ofantioxidative enzymes or otherwise exerting antioxidative effects

Salidroside has also shown protective effects against excitotoxicity induced

by glutamate or intracellular calcium in neurons.

Possible protective against excitotoxicity

4.5. Serotonin

One study assessing the interactions of rhodiola and Nicotine

(/supplements/Nicotine/) withdrawal noted that rhodiola was able to

increase neural serotonin and 5-HIAA concentrations independent of

nicotine dependency, with dose-dependent increases in serotonin at

5-40mg/kg rhodiola in control (13-183%) and nicotine dependent (11-262%)

rats, with more effects in the latter due to a relative serotonin

insufficiency. This study did not note any alterations in the 5-HT/5-HIAA

ratio nor in levels of tryptophan,

One other study has noted that the decreased levels of serotonin found in

depressive rat hippocampus' was normalized with rhodiola ingestion

(1.5-6g/kg of rhodiola with 4% salidroside), with 1.5g/kg actually being

most effective (serotonin increasing 20% higher than nonstressed control)

although not as effective as fluoxetine (2.2mg/kg; reached 48% of

control).

Rhodiola appears to be serotonergic, and increases serotonin levels in the brainand hippocampus. This appears to be general rather than context-specific

[56]

[52]

2 2[57]

[58]

[56]

[59][60][61]

[38]

[38]

[62]



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18 of 35 1/31/2014 9:31 AM

Rhodiola has also been found to increase the protein content of the 5-HT

receptor in both control and nicotine dependent rats (although much more

profoundly in the latter) and ADAPT-232 has been implicated in

downregulating the 5-HT receptor of serotonin, which is due to

suppressing expression of the gene HTR1A via tyrosol and salidroside at

3µM (6.3 and 6.6-fold downregulation). This is hypothesized to be

related to anxiolysis, as activation of the 5-HT receptor induces anxiety.

Rhodiola has been shown to alter expression of serotonin receptors, with moreof the 5-HT subset and possibly suppressive effects on 5-HT subsets

4.6. Fatigue and Stress

One meta-analysis investigating fatigue in academic settings assessing

the following studies with students given 100mg SHR-5 for 20 days,

660mg of a product called Rhodaxon (rhodiola root extract, unspecified) for

20 days, 100mg Rhodiola for 2 days, 170mg SHR-5 for 42 days,

and 370-555mg SHR-5 for a single dose (work related stress). Overall,

these studies suggest that usage of rhodiola is associated with

improvements in cognitive fatigue, PWC exercise scores,

neuro-motoric fitness (maze drawing), reductions in processing errors,

sustained attention, reaction time, general well-being, and a

reduction in pulse rate relative to placebo treatment. Although the

reduction in fatigue perception appears to be reliable, the improvement in

both sustained attention and improved visual reaction speeds appears to

be less reliable.

Other trials conducted after this date and not included in the meta-analysis

include an open-label trial with rhodiola extract (WS1375; a 1.5-5:1

concentration) at 400mg daily (200mg twice daily) for 4 weeks showed

general benefits on perceived stress (questionnaire), improvements in

stress-induced social and work dysfunction, and reductions in fatigue.

Appears to be effective, either acutely or with daily supplementation, for reducingperceived fatigue and the subsequent impairment to cognition that results fromfatigue in otherwise healthy persons subject to stress or a high workload

One trial in persons with chronic fatigue related to stress (not necessarily

'chronic fatigue syndrome') was able to find a significant protective effect of

rhodiola (576mg SHR-5 for 28 days) against stress as assessed by the

Pines’ burnout score.

1A

[38]

3

[63]

3[64]

1A 3

[65]

[66]

[4] [67] [68]

[69]

[68][66][4][69] [66]

[66] [4]

[67] [67] [66][4]

[66]

[65]

[70]

[19]



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19 of 35 1/31/2014 9:31 AM

In chronically fatigued people, rhodiola may have some efficacy in attenuatingfatigue

4.7. Appetite

In female rats conditioned to binge eat to highly palatable foods in

response to stress, rhodiola (3% rosavins and 3.12% salidroside) one hour

prior to binge eating there appeared to be a significant reduction in binge

eating with 10mg/kg and 20mg/kg abolished the binge eating. This was

apparently due to the salidroside content, and rhodiola did not have any

apparent effect on eating patterns that weren't stress induced binge

eating. Another study that noted anorectic (appetite suppressing) effects

of stress has also noted normalization with rhodiola. These bidirectional

effects are similar to those seen with Panax ginseng (/supplements

/Panax+ginseng/) and suggest a common mechanism, and one study has

noted that the reduction in binge eating seen with salidroside is synergistic

with Hypericum perforatum (/supplements/Hypericum+perforatum/).

This is thought to be more due to the adaptogenic effects of rhodiola rather

than the serotonergic effects, as serotonergic drugs (fluoxetine,

sibutramine) reduce food intake universally.

Rhodiola appears to regulate the interaction between stress and appetite, andalthough human evidence is lacking animal evidence suggests it can attenuate orotherwise abolish both binge eating and appetite suppression from stress. Theseeffects may merely be from reducing the effects of stress rather than per seinfluences on appetite, and although there is serotonergic actions of rhodiolathere is no evidence to suggest it can reduce appetite like 5-HTP (/supplements/5-HTP/) supplementation

4.8. Depression

In animal models, rhodiola has been noted to exert anti-depressive effects

in a forced swim test at 10-20mg/kg bodyweight (3% rosavins and 1%

salidroside content).

Rhodiola has been reported to reduce the side-effect profile of tricyclic

antidepressants when taken alongside the TCA pharmaceutical, which

appears to also apply to Eleutherococcus senticosus (/supplements

/Eleutherococcus+senticosus/).

In persons with mild to moderate depression given either 340mg or 680mg

of rhodiola (SHR-5) daily for 42 days noted that treatment reduced total

symptoms of depression as assessed by the BDI and HAMD rating scales

[71]

[71]

[72]

[73]

[74]

[75]

[76]



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20 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Cardiovascular+Health)

(no dose-dependence noted on HAMD and a trend for dose-dependence

on BDI, symptoms being reduced to 65-70% of baseline value on HAMD

and halved with the higher dose according to BDI) with improvements in

insomnia and emotional instability, and only the higher dose being

associated with improved sense of well being.

Appears to reduce depressive symptoms when taken as a daily supplement, andthe degree of improvement in the prelimianry evidence appears to be quite large

4.9. Anxiety

It is thought that rhodiola may aid anxiety secondary to its adaptogenic

abilities, with the increase in serotonin seen with rhodiola not likely a

concern for anxiogenic effects as the receptor that mediates anxiety from

serotonin (5-HT ) appears to be downregulated by rhodiola.

10-20mg/kg of rhodiola (3% rosavins and 1% salidroside) one hour prior to

a light/dark exploration test has been found to have some minor anxiolytic

effects with no apparent dose-dependency. In humans, there appears to

be improvements in generalized anxiety disorder with rhodiola

supplementation at 340mg over 10 weeks; this study was open-label.

Rhodiola is suspected to have anxiolytic effects, but currently there is insufficientevidence to support it. Preliminary evidence looks promising

4.10. Pain

A study assessing the nocioreceptive interactions with rhodiola failed to

find a significant reduction in pain as assessed by a tail-flick test in animals

given an active dose of rhodiola.

5.

Cardiovascular Health

5.1. Cardiac Tissue

In cardiac muscle cells (H9c2 cell line) subject to ischemia/reperfusion

injury, both salidroside (50-200µM) and tyrosol (125-500µM) or their

combination were able to greatly reduce the damage to the cells as

measured by apoptosis rates, which was attributed to inhibition of JNK

activation where tyrosol and salidroside was additive (a reference drug for

JNK inhibition also mimicked the cardioprotective effects). This inhibition

[18]

[38][62]

3[64]

[75]

[77]

[75]

[78]



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21 of 35 1/31/2014 9:31 AM

may account for results seen elsewhere where salidroside protected

cardiomyocytes from ischemia via inhibiting mitochondrial-dependent

apoptosis (JNK acts on the mitochondria to induce apoptosis ). This

inhibition of JNK may come secondary to antioxidant effects, since ROS

activates JNK in this cell line (H9c2) and salidroside confers and

antioxidative potential, and the antioxidative effects may also underlie

less N-acetylglucosamine linkages (an alternate theory of

cardioprotection from salidroside).

Elsewhere, salidroside has been noted to protect the heart from cell death

induced by hypoxia, and oxidative damage by H O .

Appears to have cardioprotective effects at the level of the heart tissue in vitrowhich appears to mostly be related to antioxidative effects of the activecompounds (tyrosol and salidroside)

In diabetic rats showing signs of heart failure, 75mg/kg of a 95% ethanolic

extract of rhodiola for 21 days was able to preserve blood pressure

(reduced in diabetic rats with heart failure) and improve cardiac output via

PPARδ dependent mechanisms. The level of PPARδ protein and mRNA

levels in the hearts of diabetic rats were reduced compared to control, and

rhodiola ingestion normalized these parameters. PPARδ is a receptor

that is known to regulate ionotrophic function when expressed in

cardiomyocytes (heart muscle cells).

Has been noted to have some bioactivity following oral ingestion and isdependent on the actions of PPARδ

One study using isolated salidroside at 600mg daily in breast cancer

patients started 1 week prior to chemotherapy noted that the reduction in

systolic function (as assessed by Strain Rate Imaging) induced by

epirubicin (a cardiotoxic anthracycline that is highly effective in breast

cancer ) was abolished by salidroside, and the increase in plasma

ROS found with placebo did not significantly occur with salidroside.

May have cardioprotective effects against anthracycline drugs similar to CoQ10(/supplements/Coenzyme+Q10/), although protection from rhodiola occurs at alarge dose of isolated salidroside

5.2. Blood Cells

Hematopoietic stem cells (a self-renewing source of pluripotent stem cells

[79] [80][81]

[82]

[83]

[84]

[85]2 2

[86]

[87]

[87]

[88][89][90]

[91][92]

[93]



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22 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Interactions+with+Glucose+Metabolism)

in bone marrow ) experience an increase in DNA synthesis after

incubation with salidroside (secondary to stimulating PARP-1 activity)

and red blood cells experience protection form oxidative damage (from

inducing thioredoxin and glutathione peroxidase) and appeared to

augment the efficacy of erythropoeitin in vitro. The induction of PARP-1

appears to also occur in lymphocytes, and has been confirmed in mice at

an oral dose of 75mg/kg; this PARP-1 activity appeared to be vital for

antioxidative effects.

Elsewhere, the mRNA expression of erythropoietin (EPO) has been found

to be induced in liver and kidney cells via isolated salidroside, which was

thought to be due to HIF-1α accumulation within the cell.

5.3. Blood Pressure

Rhodiola water extract appears to have ACE inhibiting effects with around

30% inhibition of 100-200µg/mL in vitro and 50% at 500µg/mL. This ACE

inhibitory effect has been noted elsewhere with a 12% ethanolic extract of

rhodiola with 38.5% inhibition.

6.

Interactions with Glucose Metabolism

6.1. Absorption

Rhodiola water extracts appear to have α-glucoside inhibitory potential,

where 100-200µg/mL reached absolute in vitro inhibition and 50µg/mL

inhibited just under 50% of enzyme activity; this inhibitory effect was

synergistic with cranberry extract, as the inhibitory effects of rhodiola were

preserved when in a 3:1 mixture with cranberry water extract. Rhodiola

was determined to have an IC of 93µg/mL on α-glucoside and an IC of

100µg/mL on α-amylase. This inhibition has been replicated elsewhere

with IC values for α-glucoside (44.7-52.3µg/mL) and α-amylase

(173.4µg/mL) which is thought to be linked to tyrosol (IC of 70.8µg/mL)

and the salidroside content.

Appears to have mechanisms to reduce carbohydrate absorption, but does notappear to be overly potent in this regard. Currently no studies assessingcarbohydrate absorption in a living model

6.2. Mechanisms

Salidroside appears to reduce advanced glycemic end product (AGE)

[94]

[95]

[96]

[95]

[97]

[98]

[99]

[98]

80 80[98]

50

50[99]

[100]



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23 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Inflammation+and+Immunology)

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Physical+Exercise+and+Performance)

formation in mice injected with D-galactosamine (an accelerated aging

model that is at least partially due to the AGE production )

where high doses of 1,000mg/kg salidroside reduced the AGE content in

serum to 62% of galactosamine control yet fully preserved motor

function.

6.3. Interventions

Salidroside has shown hypoglycemic activity in alloxan-induced diabetic

rats at 50, 100, and 200mg/kg oral intake for 28 days in a time and dose

depedent manner (with no significant differences between doses). The

highest dose of salidroside at 28 days was able to normalize blood glucose

levels similar to non-diabetic control. Another study using db/db

diabetic rats and 200mg/kg of rhodiola for 12 weeks noted that rhodiola

was effective as 200mg/kg Cinnamon (/supplements/Cinnamon/) in

reducing blood glucose (51.4-54.2% lower than control) and no time

dependence was noted.

7.

Inflammation and Immunology

7.1. Aging

The age-related suppression in T-lymphocyte proliferation and IL-2

secretion (from a mitogen) appears to be abolished with ingestion of

1,000mg/kg salidroside in mice which has been noted in rats.

8.

Physical Exercise and Performance

8.1. Mechanisms

Salidroside has been noted to active AMPK in skeletal muscle cells and

increased glucose uptake in a concentration dependent manner between

1.25-80µM with no dose outperforming the active control (insulin at

100nM). This study also noted that insulin-induced glucose uptake was

slightly enhanced with salidroside.

One study using rhodiola supplementation (170mg daily for 4 weeks) noted

a reduced fatty acid circulating level during a VO max test (from

12.86+/-1.62mg/dL to 7.31+/-1.31mg/dL) without significantly affecting

[101][102] [103]

[104]

[105]

[105]

[106]

[104] [107]

[108]

[108]

2



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24 of 35 1/31/2014 9:31 AM

glucose, which was associated with increased antioxidative parameters in

serum and less biomarkers of muscle damage. Lactate levels were also

reduced after exercise when measured at 3 minutes into recovery (50%

lower than control), 6 minutes (42%), and 9 minutes (33%).

8.2. Blood Oxygenation

In studies assessing blood oxygenation, Rhodiola has twice failed to

significantly influnce this parameter relative to placebo.

8.3. Physical Fatigue and Performance

Currently, one meta-analysis has assessed the interaction of rhodiola

supplementation on physical performance or physical fatigue. Of the 7

trials included in this analysis, they have used 660mg of rhodiola root

extract (Rhodaxon) for 30 days prior to exercise, 100mg of rhodiola for 4

days, 250mg for 15-22 days preceding the test (1,000mg on the day

of), 447mg acutely, 288mg of SHR-5 for 5 days, 100mg SHR-5

for 20 days, and 660mg of a product called Rhodaxon (rhodiola root

extract, unspecified) for 20 days. Most of the trials assessed in this

meta-analysis were relatively minor in regards to physical capacity, and the

observed benefits seem to be related to reducing the neural sensation of

fatigue and allowing more physical work to be conducted (effective in

cycling tests but ineffective in hypoxia and photon emission ).

In regards to physical fatigue not related to exercise, rhodiola appears to have asignificant protective and rehabilitative effect. This has been tested in moderateto high stress situations such as in physicians (doing rounds) or students duringexam periods

Rhodiola has been associated with an increased VO max and time to

exhaustion on a cycling test with another study performing a VO max

test (and not reporting on the outcome of said test) noting a reduction

creatine kinase and C-reactive protein release from the test relative to

placebo. In other studies merely assessing cardiovascular output on a

cycling test (in part of a battery of tests on fatigue) there does appear to be

benefit with rhodiola relative to placebo, which has been tested in one

study (acute dose of 3mg/kg SHR-5) which noted that rhodiola taken prior

to a 10k bicycle ride showed significantly reduced time to complete the ride

(25.4 minutes relative to 25.8 minutes) and reduced heart rate during the

warmup (136+/-17 relative to placebo's 140+/-17) but not during exericse,

which alongside average power output and cadence only trended towards

improvement. This study was conducted in recreationally fit women,

[109]

[109]

[110][111]

[65]

[112]

[67]

[111] [110] [113]

[66]

[4]

[66][4] [110] [113]

2[67]

2

[112]

[66][4]

[114]



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25 of 35 1/31/2014 9:31 AM

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Fat+Mass+and+Obesity)

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Bone+Mass+and+the+Skeleton)

and the subjects reported less subjective fatigue after consumption of

Rhodiola Rosea, and is duplicated in Medline.

Some other studies are confounded with Cordyceps sinensis

(/supplements/Cordyceps/) (no significant effect of supplementation with

300mg rhodiola with 2.5% salidroside on VO max of trained cyclists),

Cordyceps and minerals (same dose of rhodiola and again a failure of 2

weeks of supplementation to improve performance), or 5mg Zinc

(/supplements/Zinc/) with 200mg rhodiola in elite rowers, where despite

increasing plasma anti-oxidant capacity there was no effect on power

output or time to complete a 2,000m rowing test. Other studies using

trained or elite athletes note that 170mg of rhodiola for 4 weeks trended to

but failed to significantly increase VO max.

Mixed effects when looking at the interaction of rhodiola and physical exercise,with some benefit seen with higher doses in untrained persons but moremoderate doses in trained athletes not having a significant ergogenic effect.Studies are a bit too hetereogeneous to compare (studies in elite athletes areconfounded with inclusion of other nutrients, and it is unclear if the benefit seenin the other studies is due to higher dosages or due to training status)

9. Fat Mass

and Obesity

9.1. Mechanisms

Rhodiola appears to be able to prevent accumulation of lipids during

adipocyte differentiation in vitro at 1mg/mL (with Tyrosol inhibiting lipid

accumulation at 0.1-1mg/mL) with lower concentrations not highly

effective.

10. Bone

Mass and the Skeleton

10.1. Mechanisms

Salidroside in MC3T3-E1 cells (bone) at 0.1-10µM concentration is able to

reduce the oxidative damage done by H O , with 0.1µM of salidroside

being as effective as the other concentrations and as effective as the active

control of N-Acetylcysteine (10mM). The mechanisms that normally

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Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Interactions+with+Hormones)

proceeded following oxidative damage were thus inhibited.

When supplementing salidroside (5-20mg/kg) to ovarectomized rats, there

was a dose-dependent increase in bone mineral density with the higher

dose preserving 55% of bone mass of true control (relative to

ovarectomized control femur).

May be able to attenuate the rate of bone loss via antioxidative effects

11.

Interactions with Oxidation

11.1. Mechanisms

Rhodiola, via the salidroside component, appears to induce PARP-1 activity

which appears crucial for in vivo protection of DNA from H O , which

has been noted in red and white blood cells as well as fibroblasts.

PARP-1 is an NAD(+) dependent enzyme that is activated by damaged

DNA and acts to preserve DNA integrity and induce repair which has

been noted with salidroside in mice.

Salidroside is known to increase protein levels of the antioxidant enzymes

thioredoxin-1 and glutathione peroxidase with heme

oxygenase-1 (HO-1) (contested ), peroxiredoxin-I, catalase,

and superoxide dismutase having been implicated. As many of these

enzymes tend to be catered towards hydrogen peroxide (H O ) that radical

seems to be where most antioxidative defense comes from salidroside in

vitro in bone, red blood cells, neurons, fibroblasts,

and liver cells.

One study has concluded, however, that antioxidative effects cannot fully

explain cytoprotective effects of rhodiola.

Salidroside appears to both activate antioxidant enzymes and to also act uponPARP-1 and induce DNA repair machinery. The antioxidative effects seem to bebest demonstrated with hydrogen peroxide

12.

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Rhodiola rosea is a

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touted to promote






Rhodiola is also

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Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Interactions+with+Organ+Systems)

Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Interactions+with+Cancer)

Interactions with Hormones

12.1. Estrogen

A standardized extract of rhodiola (3% rosavins and 1% salidroside) is able

to competitively inhibit estrogen binding to the receptor in a concentration

dependent manner and when given to ovarectomized rats fails to show

estrogenic effects (and instead caused a nonsignificant anti-estrogenic

trend in some rats due to increasing the metabolism of estradiol).

Preliminary evidence suggests that Rhodiola Rosea is anti-estrogenic

13.

Interactions with Organ Systems

13.1. Liver

One study has noted that salidroside is able to induce mesenchymal cell

division towards hepatocytes and, when assessing biomarker proteins

(EROD, PROD, and LDL uptake) salidroside at 2µM appears to be as

effective as hepatocyte growth factor (HGF; 20ng/mL) for inducing

mesenchymal division over 4 weeks.

Appears to induce proliferation of liver cells from a common stem cell precursor,practical significance of these results currently unknown

Salidroside (25-100mg/kg) has been noted to reduce oxidative stress in the

liver that is the result of exhaustive exercise which has also been noted

with p-tyrosol, rosavin, and rosidrin (as well as rhodiola extract

consumption).

14.

Interactions with Cancer

14.1. Bladder

A small trial (n=12) has associated rhodiola supplementation with half the

risk for bladder cancer relapse |published=1995

Mar-Apr|authors=Bocharova OA, Matveev BP, Baryshnikov AIu, Figurin KM,

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Rhodiola rosea is a

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Rhodiola is also

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Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Nutrient-Nutrient+Interactions)

Serebriakova RV, Bodrova NB|journal=Urol Nefrol (Mosk)] and a later in

vitro test noted that salidroside had suppressive effects on p53 deficient

cells which was partly dependent on TSC2 expression; there was

ultimately an activation of AMPK and suppression of mTOR signalling and

its downstream targets (S6 and 4E-BP1) resulting in autophagic cell

death. Concentrations as low as 5µg/mL were active on cancer cells,

and 25µg/mL was unable to suppress noncancerous cells.

14.2. Breast

Salidroside has been noted to induce apoptosis in breast cancer cells on

both MDA-MB-231 and MCF-7 cells, with an IC of 10µM and 20µM

respectively. Salidroside was confirmed in this study to not be an

estrogen receptor antagonist (which can induce apoptosis in MCF-7 cells)

and was noted to induce apoptosis in both cell lines in a concentration

dependent manner. Elsewhere, the IC for salidroside in inhibiting

proliferation was calculated at 3.2µg/mL (MDA-MB-231) and 6.5µg/mL

(MCF-7).

Salidroside has also noted protection against the cardiotoxic effects of a

common breast cancer chemotherapeutic known as epirubicin.

14.3. Stomach

Salidroside has shown inhibitory effects on the gastric cancer cell line

SGC-7901 with an IC value for inhibiting cell proliferation of

6.1µg/mL.

15.

Nutrient-Nutrient Interactions

15.1. Nicotine

Nicotine (/supplements/Nicotine/) is the primary stimulatory alkaloid in

cigarettes and some smoking aids. In mice conditioned to nicotine via

injections who exhibited withdrawal behaviours (anxiety and locomotor

changes) noted that oral ingestion of Rhodiola at 10-20mg/kg during

nicotine therapy reduced anxiety by more than 50% (appeared to be dose

dependent, but 10mg/kg was not significantly different than 20mg/kg) with

similar effects seen with acute usage of Rhodiola (20mg/kg) after nicotine

was ceased. This study also noted that Rhodiola was able to abolish all

somatic symptoms of withdrawal in these mice. A later study in rats

with similar methodlogy confirmed these effects and noted that the

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Rhodiola rosea is a

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Rhodiola is also

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mechanisms appear to be serotonergic in nature as the serotonin receptor

antagonist (WAY 100635) abolished the effects and nicotine treated

animals appeared to have lower levels of serotonin in their brain (which

Rhodiola normalized).

Limited evidence, but rhodiola at fairly reasonable oral doses (20mg/kg in miceand 40mg/kg in rats correlates to a human estimated dose of 1.2mg/kg or 80mgfor a 150lb person) can greatly suppress or eliminate physical symptoms ofsmoking cessation (nicotine withdrawal). Cognitive symptoms (anxiety beingmeasured) are somewhat less affected

15.2. Weikang Keli

Weikang Keli is a Traditional Chinese Medicine (/supplements

/Traditional+Chinese+Medicine/) for gastric cancer which consists of

Atractylodis macrocephalae, Curcumae Aeruginosae, the rhizome of

Pinelliae, Codonopsis pilosula (/supplements/Codonopsis+pilosula/),

rhodiola rosea, and Actinidia chinensis (1:1:1:2:2:2 ratio). It has been

demonstrated in SGC-7901 stomach cancer cells to inhibit proliferation in a

concentration and time dependent manner with an IC of 0.2g/mL via

autophagic mechanisms. In mice implanted with tumors,

2,400-9,600mg/kg of the herbal therapy was able to reduce tumor mass by

43%, 55%, and 57% respectively with the active control of 5-fluorouracil

(15mg/kg) reducing tumor size by 51%.

15.3. Hypericum perforatum

A study investigating the influence of Hypericum perforatum (/supplements

/Hypericum+perforatum/) on binge eating noted that 250-500mg/kg (but

not 125mg/kg) of this herb was able to reduce binge eating episodes in

female rates conditioned to hyperpalatable foods. The addition of

312mcg/kg salidroside to the ineffective dose of St.John's wort (125mg/kg)

was able to synergistically enhance the anti-binge eating effect. It

should be noted that higher doses of salidroside (20mg/kg or a 3.12%

extract; or 624mcg/kg) are able to abolish binge eating in this model.

Salidroside (from rhodiola) can make subeffective doses of St.John's wort moreeffective in aiding binge eating. Although synergistic, the practical implications ofthis are limited as rhodiola in isolation is effective in abolishing binge eating inthis rat model

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Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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Edit (/edit-section/supplements/Rhodiola+Rosea/?sec tion=Safety+and+Toxicology)16. Safety

and Toxicology

16.1. General

In human trials that use Rhodiola supplementation, there do not tend to be

side effects associated with treatment that are deemed to be clinically

relevant.

Scientific Support & ReferenceCitations

ReferencesColson SN, et al. Cordyceps sinensis- and Rhodiola rosea-based supplementation in male cyclists and its effect onmuscle tissue oxygen saturation (http://www.ncbi.nlm.nih.gov/pubmed/15903375). J Strength Cond Res. (2005)

1.

Earnest CP, et al. Effects of a commercial herbal-based formula on exercise performance in cyclists(http://www.ncbi.nlm.nih.gov/pubmed/15076794). Med Sci Sports Exerc. (2004)

2.

Skarpanska-Stejnborn A, et al. The influence of supplementation with Rhodiola rosea L. extract on selected redoxparameters in professional rowers (http://www.ncbi.nlm.nih.gov/pubmed/19478343). Int J Sport Nutr Exerc Metab.(2009)

3.

Spasov AA, Mandrikov VB, Mironova IA. The effect of the preparation rodakson on the psychophysiological and physicaladaptation of students to an academic load (http://www.ncbi.nlm.nih.gov/pubmed/10763116). Eksp Klin Farmakol.(2000)

4.

Rohloff J. Volatiles from rhizomes of Rhodiola rosea L (http://www.ncbi.nlm.nih.gov/pubmed/11867098).Phytochemistry. (2002)

5.

Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacologyand clinical efficacy (http://www.ncbi.nlm.nih.gov/pubmed/20378318). Phytomedicine. (2010)

6.

Jafari M, et al. Rhodiola: a promising anti-aging Chinese herb (http://www.ncbi.nlm.nih.gov/pubmed/17990971).Rejuvenation Res. (2007)

7.

Yousef GG, et al. Comparative phytochemical characterization of three Rhodiola species (http://www.ncbi.nlm.nih.gov/pubmed/16956631). Phytochemistry. (2006)

8.

Effects of Adaptogens on the Central Nervous System and the Molecular Mechanisms associated with their Stress -Protective Activity (http://www.mdpi.com/1424-8247/3/1/188/pdf)

9.

Mudge E, et al. Purification of Phenylalkanoids and monoterpene glycosides from rhodiola rosea L. roots by high-speedcounter-current chromatography (http://www.ncbi.nlm.nih.gov/pubmed/22811209). Phytochem Anal. (2013)

10.

Akgul Y, et al. Lotaustralin from Rhodiola rosea roots (http://www.ncbi.nlm.nih.gov/pubmed/15351122). Fitoterapia.(2004)

11.

Ming DS, et al. Bioactive compounds from Rhodiola rosea (Crassulaceae) (http://www.ncbi.nlm.nih.gov/pubmed/16220564). Phytother Res. (2005)

12.

Study on separation and purification of oligomeric proanthocyanidin from Rhodiola rosea (http://link.springer.com/article/10.1007%2Fs11703-011-1137-8)

13.

Extraction and purification of proanthocyanidins from R.Roaea (http://en.cnki.com.cn/Article_en/CJFDTOTAL-NYGN200707015.htm)

14.

Glycosides of cinnamyl alcohol from the rhizomes of Rhodiola rosea (http://link.springer.com/article/10.1007%2FBF00579423?LI=true)

15.

Guo N, et al. Simultaneous determination of salidroside and its aglycone metabolite p-tyrosol in rat plasma by liquidchromatography-tandem mass spectrometry (http://www.ncbi.nlm.nih.gov/pubmed/22525439). Molecules. (2012)

16.

Panossian A, et al. Adaptogens stimulate neuropeptide y and hsp72 expression and release in neuroglia cells(http://www.ncbi.nlm.nih.gov/pubmed/22347152). Front Neurosci. (2012)

17.

Darbinyan V, et al. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression(http://www.ncbi.nlm.nih.gov/pubmed/17990195). Nord J Psychiatry. (2007)

18.

Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of thestandardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue

19.

[65]



QuickSummary:

Rhodiola rosea is a

Traditional Chinese




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Rhodiola is also

neuroprotective and





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31 of 35 1/31/2014 9:31 AM

(http://www.ncbi.nlm.nih.gov/pubmed/19016404). Planta Med. (2009)Aslanyan G, et al. Double-blind, placebo-controlled, randomised study of single dose effects of ADAPT-232 on cognitivefunctions (http://www.ncbi.nlm.nih.gov/pubmed/20374974). Phytomedicine. (2010)

20.

Sodium-dependent Glucose Transporter Was Involved in Salidroside Absorption in Intestine of Rats(http://www.sciencedirect.com/science/article/pii/S1875536409600686)

21.

Mizuma T, et al. Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implicationof improvement of poorly absorbable drugs (http://www.ncbi.nlm.nih.gov/pubmed/1596291). Biochem Pharmacol.(1992)

22.

Morand C, et al. Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in ratplasma (http://www.ncbi.nlm.nih.gov/pubmed/11200097). Free Radic Res. (2000)

23.

Yu S, et al. Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric methodfor the determination of salidroside in rat plasma: application to the pharmacokinetics study(http://www.ncbi.nlm.nih.gov/pubmed/18088572). J Chromatogr B Analyt Technol Biomed Life Sci. (2008)

24.

Chang YW, et al. Quantitative determination of salidroside in rat plasma by on-line solid-phase extraction integratedwith high-performance liquid chromatography/electrospray ionization tandem mass spectrometry(http://www.ncbi.nlm.nih.gov/pubmed/17631426). J Chromatogr B Analyt Technol Biomed Life Sci. (2007)

25.

Hellum BH, et al. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea (http://www.ncbi.nlm.nih.gov/pubmed/19790032). Planta Med. (2010)

26.

Panossian A, et al. Pharmacokinetic and pharmacodynamic study of interaction of Rhodiola rosea SHR-5 extract withwarfarin and theophylline in rats (http://www.ncbi.nlm.nih.gov/pubmed/18844284). Phytother Res. (2009)

27.

Wiegant FA, et al. Plant adaptogens increase lifespan and stress resistance in C. elegans (http://www.ncbi.nlm.nih.gov/pubmed/18536978). Biogerontology. (2009)

28.

Hormesis and aging in Caenorhabditis elegans (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1847401/)29.McElwee JJ, et al. Evolutionary conservation of regulated longevity assurance mechanisms(http://www.ncbi.nlm.nih.gov/pubmed/17612391). Genome Biol. (2007)

30.

Partridge L, Gems D. Mechanisms of ageing: public or private (http://www.ncbi.nlm.nih.gov/pubmed/11972154). NatRev Genet. (2002)

31.

Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to theirstress-protective activity (http://www.ncbi.nlm.nih.gov/pubmed/19500070). Curr Clin Pharmacol. (2009)

32.

Schriner SE, et al. Decreased mitochondrial superoxide levels and enhanced protection against paraquat in Drosophilamelanogaster supplemented with Rhodiola rosea (http://www.ncbi.nlm.nih.gov/pubmed/19634056). Free Radic Res.(2009)

33.

Schriner SE, et al. Extension of Drosophila Lifespan by Rhodiola rosea through a Mechanism Independent from DietaryRestriction (http://www.ncbi.nlm.nih.gov/pubmed/23704949). PLoS One. (2013)

34.

Bayliak MM, Lushchak VI. The golden root, Rhodiola rosea, prolongs lifespan but decreases oxidative stress resistancein yeast Saccharomyces cerevisiae (http://www.ncbi.nlm.nih.gov/pubmed/21802922). Phytomedicine. (2011)

35.

van Diermen D, et al. Monoamine oxidase inhibition by Rhodiola rosea L. roots (http://www.ncbi.nlm.nih.gov/pubmed/19168123). J Ethnopharmacol. (2009)

36.

Inhibition of monoamine oxidase and acetylcholinesterase by Rhodiola rosea L (https://www.thieme-connect.com/ejournals/abstract/10.1055/s-0028-1084200)

37.

Mannucci C, et al. Serotonin involvement in Rhodiola rosea attenuation of nicotine withdrawal signs in rats(http://www.ncbi.nlm.nih.gov/pubmed/22921986). Phytomedicine. (2012)

38.

Blum K, et al. Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substanceseeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: ahypothesis (http://www.ncbi.nlm.nih.gov/pubmed/17467918). Med Hypotheses. (2007)

39.

Ciumaşu-Rîmbu M, Popa L, Vulpoi C. Neuropeptide Y stimulation as primary target for preventive measures ofmaladaptative cardiovascular reactions in occupational chronic stress exposure (http://www.ncbi.nlm.nih.gov/pubmed/23272529). Rev Med Chir Soc Med Nat Iasi. (2012)

40.

Panossian A, et al. Adaptogens exert a stress-protective effect by modulation of expression of molecular chaperones(http://www.ncbi.nlm.nih.gov/pubmed/19188053). Phytomedicine. (2009)

41.

Panossian A, Wagner H. Stimulating effect of adaptogens: an overview with particular reference to their efficacyfollowing single dose administration (http://www.ncbi.nlm.nih.gov/pubmed/16261511). Phytother Res. (2005)

42.

Sheng QS, et al. Salidroside promotes peripheral nerve regeneration following crush injury to the sciatic nerve in rats(http://www.ncbi.nlm.nih.gov/pubmed/23358450). Neuroreport. (2013)

43.

Ma J, et al. Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury(http://www.ncbi.nlm.nih.gov/pubmed/20438804). Neurosci Lett. (2010)

44.

Tidwell JL, Houenou LJ, Tytell M. Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration(http://www.ncbi.nlm.nih.gov/pubmed/15270081). Cell Stress Chaperones. (2004)

45.

Houenou LJ, et al. Exogenous heat shock cognate protein Hsc 70 prevents axotomy-induced death of spinal sensoryneurons (http://www.ncbi.nlm.nih.gov/pubmed/9222601). Cell Stress Chaperones. (1996)

46.

Protective Effects of a Rhodiola Crenulata Extract and Salidroside on Hippocampal Neurogenesis againstStreptozotocin-Induced Neural Injury in the Rat (http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029641)

47.

Pretreatment with Rhodiola Rosea Extract Reduces Cognitive Impairment Induced by IntracerebroventricularStreptozotocin in Rats: Implication of Anti-oxidative and Neuroprotective Effects (http://www.sciencedirect.com/science/article/pii/S0895398809600623)

48.

Effects of Rhodiola rosea extract on passive avoidance tests in rats (http://link.springer.com/article/10.2478%2Fs11536-012-0124-7)

49.

Petkov VD, et al. Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory(http://www.ncbi.nlm.nih.gov/pubmed/3751623). Acta Physiol Pharmacol Bulg. (1986)

50.

Lazarova MB, et al. Effects of meclofenoxate and Extr. Rhodiolae roseae L. on electroconvulsive shock-impairedlearning and memory in rats (http://www.ncbi.nlm.nih.gov/pubmed/3095599). Methods Find Exp Clin Pharmacol.(1986)

51.



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Rhodiola is also

neuroprotective and





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32 of 35 1/31/2014 9:31 AM

Zhang J, et al. Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress andinflammatory mediators in rat hippocampus (http://www.ncbi.nlm.nih.gov/pubmed/23396166). Behav Brain Res. (2013)

52.

Qu ZQ, et al. Pretreatment with Rhodiola rosea extract reduces cognitive impairment induced byintracerebroventricular streptozotocin in rats: implication of anti-oxidative and neuroprotective effects(http://www.ncbi.nlm.nih.gov/pubmed/19950527). Biomed Environ Sci. (2009)

53.

Fintelmann V, Gruenwald J. Efficacy and tolerability of a Rhodiola rosea extract in adults with physical and cognitivedeficiencies (http://www.ncbi.nlm.nih.gov/pubmed/17901042). Adv Ther. (2007)

54.

Neuroprotective Effects of Salidroside in the PC12 Cell Model Exposed to Hypoglycemia and Serum Limitation(http://www.springerlink.com/content/m1324p7h35u44607/)

55.

Zhang L, et al. Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y humanneuroblastoma cells (http://www.ncbi.nlm.nih.gov/pubmed/20615444). Neurochem Int. (2010)

56.

Chen X, et al. Protective effect of salidroside against H2O2-induced cell apoptosis in primary culture of rat hippocampalneurons (http://www.ncbi.nlm.nih.gov/pubmed/19554425). Mol Cell Biochem. (2009)

57.

Shi TY, et al. Neuroprotective effects of Salidroside and its analogue tyrosol galactoside against focal cerebral ischemiain vivo and H2O2-induced neurotoxicity in vitro (http://www.ncbi.nlm.nih.gov/pubmed/22095090). Neurotox Res. (2012)

58.

Cao LL, Du GH, Wang MW. The effect of salidroside on cell damage induced by glutamate and intracellular freecalcium in PC12 cells (http://www.ncbi.nlm.nih.gov/pubmed/16753799). J Asian Nat Prod Res. (2006)

59.

Chen X, et al. Salidroside attenuates glutamate-induced apoptotic cell death in primary cultured hippocampal neuronsof rats (http://www.ncbi.nlm.nih.gov/pubmed/18680733). Brain Res. (2008)

60.

Palumbo DR, et al. Rhodiola rosea extract protects human cortical neurons against glutamate and hydrogen peroxide-induced cell death through reduction in the accumulation of intracellular calcium (http://www.ncbi.nlm.nih.gov/pubmed/22086763). Phytother Res. (2012)

61.

Chen QG, et al. The effects of Rhodiola rosea extract on 5-HT level, cell proliferation and quantity of neurons atcerebral hippocampus of depressive rats (http://www.ncbi.nlm.nih.gov/pubmed/19403286). Phytomedicine. (2009)

62.

Panossian A, et al. Synergy and Antagonism of Active Constituents of ADAPT-232 on Transcriptional Level of MetabolicRegulation of Isolated Neuroglial Cells (http://www.ncbi.nlm.nih.gov/pubmed/23430930). Front Neurosci. (2013)

63.

Kennett GA, et al. Anxiolytic-like actions of the selective 5-HT4 receptor antagonists SB 204070A and SB 207266A inrats (http://www.ncbi.nlm.nih.gov/pubmed/9225297). Neuropharmacology. (1997)

64.

Hung SK, Perry R, Ernst E. The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomizedclinical trials (http://www.ncbi.nlm.nih.gov/pubmed/21036578). Phytomedicine. (2011)

65.

Spasov AA, et al. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiolarosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeatedlow-dose regimen (http://www.ncbi.nlm.nih.gov/pubmed/10839209). Phytomedicine. (2000)

66.

De Bock K, et al. Acute Rhodiola rosea intake can improve endurance exercise performance(http://www.ncbi.nlm.nih.gov/pubmed/15256690). Int J Sport Nutr Exerc Metab. (2004)

67.

Darbinyan V, et al. Rhodiola rosea in stress induced fatigue--a double blind cross-over study of a standardized extractSHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty(http://www.ncbi.nlm.nih.gov/pubmed/11081987). Phytomedicine. (2000)

68.

Shevtsov VA, et al. A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo andcontrol of capacity for mental work (http://www.ncbi.nlm.nih.gov/pubmed/12725561). Phytomedicine. (2003)

69.

Edwards D, Heufelder A, Zimmermann A. Therapeutic effects and safety of Rhodiola rosea extract WS® 1375 insubjects with life-stress symptoms--results of an open-label study (http://www.ncbi.nlm.nih.gov/pubmed/22228617).Phytother Res. (2012)

70.

Cifani C, et al. Effect of salidroside, active principle of Rhodiola rosea extract, on binge eating(http://www.ncbi.nlm.nih.gov/pubmed/20837037). Physiol Behav. (2010)

71.

Mattioli L, Perfumi M. Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats(http://www.ncbi.nlm.nih.gov/pubmed/17259204). J Psychopharmacol. (2007)

72.

Micioni Di Bonaventura MV, et al. Effect of Hypericum perforatum Extract in an Experimental Model of Binge Eating inFemale Rats (http://www.ncbi.nlm.nih.gov/pubmed/22997570). J Obes. (2012)

73.

Cifani C, et al. A preclinical model of binge eating elicited by yo-yo dieting and stressful exposure to food: effect ofsibutramine, fluoxetine, topiramate, and midazolam (http://www.ncbi.nlm.nih.gov/pubmed/19125237).Psychopharmacology (Berl). (2009)

74.

Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3% rosavin and 1%salidroside Rhodiola rosea L. extract in mice (http://www.ncbi.nlm.nih.gov/pubmed/17072830). Phytother Res. (2007)

75.

The Use of Herbal Adaptogens together with Tricyclic Antidepressants in Patients with Psychogenic Depressions(http://www.scicompdf.se/rosenrot/brichenko3.pdf)

76.

Bystritsky A, Kerwin L, Feusner JD. A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD)(http://www.ncbi.nlm.nih.gov/pubmed/18307390). J Altern Complement Med. (2008)

77.

Sun L, et al. Salidroside and tyrosol from Rhodiola protect H9c2 cells from ischemia/reperfusion-induced apoptosis(http://www.ncbi.nlm.nih.gov/pubmed/22771701). Life Sci. (2012)

78.

Zhong H, et al. Salidroside attenuates apoptosis in ischemic cardiomyocytes: a mechanism through a mitochondria-dependent pathway (http://www.ncbi.nlm.nih.gov/pubmed/21160132). J Pharmacol Sci. (2010)

79.

He H, et al. Activation of the JNK pathway is important for cardiomyocyte death in response to simulated ischemia(http://www.ncbi.nlm.nih.gov/pubmed/10556976). Cell Death Differ. (1999)

80.

Role of the Mitochondrial Permeability Transition in Myocardial Disease (http://circres.ahajournals.org/content/93/4/292.short)

81.

Aggeli IK, Gaitanaki C, Beis I. Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation ofheme oxygenase-1 mRNA in H9c2 cells (http://www.ncbi.nlm.nih.gov/pubmed/16531007). Cell Signal. (2006)

82.

Lee OH, et al. Rhodiola-induced inhibition of adipogenesis involves antioxidant enzyme response associated withpentose phosphate pathway (http://www.ncbi.nlm.nih.gov/pubmed/20623718). Phytother Res. (2011)

83.

Wu T, et al. Cardioprotection of salidroside from ischemia/reperfusion injury by increasing N-acetylglucosamine linkageto cellular proteins (http://www.ncbi.nlm.nih.gov/pubmed/19376110). Eur J Pharmacol. (2009)

84.



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Zhang J, et al. Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated andVEGF-mediated pathway (http://www.ncbi.nlm.nih.gov/pubmed/19326475). Eur J Pharmacol. (2009)

85.

Zhu Y, et al. Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependentpathway (http://www.ncbi.nlm.nih.gov/pubmed/21563965). DNA Cell Biol. (2011)

86.

Cheng YZ, et al. Increase of myocardial performance by Rhodiola-ethanol extract in diabetic rats(http://www.ncbi.nlm.nih.gov/pubmed/23044195). J Ethnopharmacol. (2012)

87.

Cheng L, et al. Cardiomyocyte-restricted peroxisome proliferator-activated receptor-delta deletion perturbs myocardialfatty acid oxidation and leads to cardiomyopathy (http://www.ncbi.nlm.nih.gov/pubmed/15475963). Nat Med. (2004)

88.

Cheng L, et al. Peroxisome proliferator-activated receptor delta activates fatty acid oxidation in cultured neonatal andadult cardiomyocytes (http://www.ncbi.nlm.nih.gov/pubmed/14684157). Biochem Biophys Res Commun. (2004)

89.

Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome(http://www.ncbi.nlm.nih.gov/pubmed/16511591). J Clin Invest. (2006)

90.

Minotti G, et al. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity andcardiotoxicity (http://www.ncbi.nlm.nih.gov/pubmed/15169927). Pharmacol Rev. (2004)

91.

Elliott P. Pathogenesis of cardiotoxicity induced by anthracyclines (http://www.ncbi.nlm.nih.gov/pubmed/16781283).Semin Oncol. (2006)

92.

Zhang H, et al. Protective effects of salidroside on epirubicin-induced early left ventricular regional systolic dysfunctionin patients with breast cancer (http://www.ncbi.nlm.nih.gov/pubmed/22770377). Drugs R D. (2012)

93.

Orkin SH, Zon LI. Hematopoiesis: an evolving paradigm for stem cell biology (http://www.ncbi.nlm.nih.gov/pubmed/18295580). Cell. (2008)

94.

Li X, et al. Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance(http://www.ncbi.nlm.nih.gov/pubmed/22427203). Blood. (2012)

95.

Qian EW, Ge DT, Kong SK. Salidroside promotes erythropoiesis and protects erythroblasts against oxidative stress byup-regulating glutathione peroxidase and thioredoxin (http://www.ncbi.nlm.nih.gov/pubmed/20920561). JEthnopharmacol. (2011)

96.

Zheng KY, et al. Salidroside stimulates the accumulation of HIF-1α protein resulted in the induction of EPO expression:a signaling via blocking the degradation pathway in kidney and liver cells (http://www.ncbi.nlm.nih.gov/pubmed/22309741). Eur J Pharmacol. (2012)

97.

Apostolidis E, Kwon YI, Shetty K. Potential of cranberry-based herbal synergies for diabetes and hypertensionmanagement (http://www.ncbi.nlm.nih.gov/pubmed/16837438). Asia Pac J Clin Nutr. (2006)

98.

Kwon YI, Jang HD, Shetty K. Evaluation of Rhodiola crenulata and Rhodiola rosea for management of type II diabetesand hypertension (http://www.ncbi.nlm.nih.gov/pubmed/16837437). Asia Pac J Clin Nutr. (2006)

99.

Anti-diabetes functionality of Kefir culture-mediated fermented soymilk supplemented with Rhodiola extracts(http://openagricola.nal.usda.gov/Record/IND43806884)

100.

Wei H, et al. Behavioural study of the D-galactose induced aging model in C57BL/6J mice (http://www.ncbi.nlm.nih.gov/pubmed/15639175). Behav Brain Res. (2005)

101.

Cui X, et al. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damagein mice: protective effects of R-alpha-lipoic acid (http://www.ncbi.nlm.nih.gov/pubmed/16555301). J Neurosci Res.(2006)

102.

Song X, et al. Advanced glycation in D-galactose induced mouse aging model (http://www.ncbi.nlm.nih.gov/pubmed/10405984). Mech Ageing Dev. (1999)

103.

Mao GX, et al. Protective role of salidroside against aging in a mouse model induced by D-galactose(http://www.ncbi.nlm.nih.gov/pubmed/20514993). Biomed Environ Sci. (2010)

104.

Li F, et al. Protective effect of salidroside from Rhodiolae Radix on diabetes-induced oxidative stress in mice(http://www.ncbi.nlm.nih.gov/pubmed/22134398). Molecules. (2011)

105.

Kim SH, Hyun SH, Choung SY. Antioxidative effects of Cinnamomi cassiae and Rhodiola rosea extracts in liver ofdiabetic mice (http://www.ncbi.nlm.nih.gov/pubmed/16971752). Biofactors. (2006)

106.

Lu L, Yuan J, Zhang S. Rejuvenating activity of salidroside (SDS): dietary intake of SDS enhances the immuneresponse of aged rats (http://www.ncbi.nlm.nih.gov/pubmed/22367581). Age (Dordr). (2012)

107.

Li HB, et al. Salidroside stimulated glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase(http://www.ncbi.nlm.nih.gov/pubmed/18501890). Eur J Pharmacol. (2008)

108.

Parisi A, et al. Effects of chronic Rhodiola Rosea supplementation on sport performance and antioxidant capacity intrained male: preliminary results (http://www.ncbi.nlm.nih.gov/pubmed/20308973). J Sports Med Phys Fitness. (2010)

109.

Wing SL, et al. Lack of effect of Rhodiola or oxygenated water supplementation on hypoxemia and oxidative stress(http://www.ncbi.nlm.nih.gov/pubmed/12659243). Wilderness Environ Med. (2003)

110.

Walker TB, et al. Failure of Rhodiola rosea to alter skeletal muscle phosphate kinetics in trained men(http://www.ncbi.nlm.nih.gov/pubmed/17618958). Metabolism. (2007)

111.

Abidov M, et al. Extract of Rhodiola rosea radix reduces the level of C-reactive protein and creatinine kinase in the blood(http://www.ncbi.nlm.nih.gov/pubmed/15514725). Bull Exp Biol Med. (2004)

112.

Schutgens FW, et al. The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment(http://www.ncbi.nlm.nih.gov/pubmed/19170145). Phytother Res. (2009)

113.

Noreen EE, et al. The Effects of an Acute Dose of Rhodiola Rosea on Endurance Exercise Performance(http://www.ncbi.nlm.nih.gov/pubmed/22643145). J Strength Cond Res. (2012)

114.

Noreen EE, et al. The Effects of an Acute Dose of Rhodiola rosea on Endurance Exercise Performance(http://www.ncbi.nlm.nih.gov/pubmed/23443221). J Strength Cond Res. (2013)

115.

Zhang JK, et al. Protection by Salidroside against Bone Loss via Inhibition of Oxidative Stress and Bone-ResorbingMediators (http://www.ncbi.nlm.nih.gov/pubmed/23437352). PLoS One. (2013)

116.

Oka S, Hsu CP, Sadoshima J. Regulation of cell survival and death by pyridine nucleotides (http://www.ncbi.nlm.nih.gov/pubmed/22904041). Circ Res. (2012)

117.

Xu J, Li Y. Effects of salidroside on exhaustive exercise‑induced oxidative stress in rats (http://www.ncbi.nlm.nih.gov/pubmed/22948446). Mol Med Rep. (2012)

118.

Schriner SE, et al. Protection of human cultured cells against oxidative stress by Rhodiola rosea without activation of119.



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Rhodiola rosea is a

Traditional Chinese




touted to promote






Rhodiola is also

neuroprotective and





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antioxidant defenses (http://www.ncbi.nlm.nih.gov/pubmed/19486939). Free Radic Biol Med. (2009)Qian EW, Ge DT, Kong SK. Salidroside protects human erythrocytes against hydrogen peroxide-induced apoptosis(http://www.ncbi.nlm.nih.gov/pubmed/22483064). J Nat Prod. (2012)

120.

Qu ZQ, et al. Protective effects of a Rhodiola crenulata extract and salidroside on hippocampal neurogenesis againststreptozotocin-induced neural injury in the rat (http://www.ncbi.nlm.nih.gov/pubmed/22235318). PLoS One. (2012)

121.

Mao GX, et al. Salidroside protects human fibroblast cells from premature senescence induced by H(2)O(2) partlythrough modulating oxidative status (http://www.ncbi.nlm.nih.gov/pubmed/21035481). Mech Ageing Dev. (2010)

122.

Guan S, et al. Salidroside attenuates hydrogen peroxide-induced cell damage through a cAMP-dependent pathway(http://www.ncbi.nlm.nih.gov/pubmed/21512445). Molecules. (2011)

123.

Evaluation of the medicinal botanical Rhodiola rosea for estrogenicity (http://www.aacrmeetingabstracts.org/cgi/content/abstract/2004/1/663-b)

124.

Ouyang JF, et al. In-vitro promoted differentiation of mesenchymal stem cells towards hepatocytes induced bysalidroside (http://www.ncbi.nlm.nih.gov/pubmed/20604844). J Pharm Pharmacol. (2010)

125.

Huang SC, et al. Attenuation of long-term Rhodiola rosea supplementation on exhaustive swimming-evoked oxidativestress in the rat (http://www.ncbi.nlm.nih.gov/pubmed/20034236). Chin J Physiol. (2009)

126.

[The effect of a Rhodiola rosea extract on the incidence of recurrences of a superficial bladder cancer (experimentalclinical research) (http://www.ncbi.nlm.nih.gov/pubmed/7785120)

127.

Liu Z, et al. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of themTOR pathway and induction of autophagy (http://www.ncbi.nlm.nih.gov/pubmed/21520297). Mol Carcinog. (2012)

128.

Hu X, et al. Salidroside induces cell-cycle arrest and apoptosis in human breast cancer cells(http://www.ncbi.nlm.nih.gov/pubmed/20541529). Biochem Biophys Res Commun. (2010)

129.

Hu X, et al. A preliminary study: the anti-proliferation effect of salidroside on different human cancer cell lines(http://www.ncbi.nlm.nih.gov/pubmed/20309622). Cell Biol Toxicol. (2010)

130.

Mattioli L, Perfumi M. Evaluation of Rhodiola rosea L. extract on affective and physical signs of nicotine withdrawal inmice (http://www.ncbi.nlm.nih.gov/pubmed/19939867). J Psychopharmacol. (2011)

131.

Huo J, et al. Chinese medicine formula "Weikang Keli" induces autophagic cell death on human gastric cancer cell lineSGC-7901 (http://www.ncbi.nlm.nih.gov/pubmed/23141426). Phytomedicine. (2013)

132.

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QuickSummary:

Rhodiola rosea is a

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Rhodiola is also

neuroprotective and





History (/history




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Rhodiola Rosea - Scientific Review on Usage, Dosage, Side Effects _ Examine

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