Eleuthero (Siberian Ginseng) Root Dosage & Side Effects

Eleuthero is an Eastern adaptogen that helps your body fight off a cold. It’s also packed with bioactive compounds. Unsure about its safety and the dosage you should use? Read on for our evidence-based guide.

What is Eleuthero?

Definition

Also known as Siberian ginseng, eleuthero is an herb with the scientific names Eleutherococcus senticosus or Acanthopanax senticosus. Around the world, it may also be called Ciwujia, Shigoka, Goka, Ezoukogi, or Kan Jang (when combined with green chiretta). It is a staple of traditional medicine in the Far East, especially in China, Korea, and eastern Russia [1, 2, 3, 4, 5, 6].

According to these traditions, eleuthero is an adaptogen: a substance that keeps the body functioning normally under stress [7].

Eleuthero belongs to the same plant family as Asian and American ginseng (Araliaceae). However, Asian and American ginseng both belong to a different genus further up the botanical tree called Panax, while eleuthero belongs to Eleutherococcus. Being a distant cousin of these other ginsengs, eleuthero contains a different set of bioactive compounds [8].

Eleuthero is a flowering shrub. Its root, bark, leaves, and berries all contain bioactive compounds that may have positive health effects [9, 10].

Components

The roots, berries, and leaves of eleuthero each contain multiple bioactive compounds. The specific compounds in each part of the plant may be different, and so their health benefits may also vary. Most studies on the health benefits of eleuthero focus on the root and bark [10].

Eleuthero berries contain high levels of antioxidants and potential cancer-fighting compounds; they are also high in important minerals like potassium, calcium, and magnesium. These berries have long been added to fermented wines in China and Russia [9].

Eleutherosides

The most important bioactive compounds in eleuthero belong to a chemical family called eleutherosides; these are eleutherosides A through E. Of these, the ones with the greatest effect are eleutherosides B (syringin) and E [11].

These two compounds are being investigated for anticancer and anti-diabetic effects [11].

Sesamin

Sesamin is an active compound that was first discovered in sesame seeds. Sesamin from eleuthero may help protect nerve and brain cells from damage. Sesamin may also improve liver function and reduce cholesterol [12, 13].

Isofraxidin

Researchers isolated isofraxidin from eleuthero bark and consider it may have the potential to fight liver cancer [14].

Oleanolic Acid

Oleanolic acid is a common compound that is found in many plants, including eleuthero. This compound is a strong antioxidant that may also fight inflammation and improve liver function [15, 16].

Ursolic Acid

Ursolic acid is found in many different plants, including eleuthero. It can be taken as a supplement and is reported to decrease inflammation, fight cancer, prevent diabetes, protect the heart, and lower cholesterol. Researchers are currently investigating their anticancer effects [17, 18, 19].

Possible Mechanisms of Eleuthero

Eleuthero’s mechanism of action is complex because it contains an abundance of active compounds. Each compound may have unique effects, and these effects may add up or counteract each other.

AMPK Activation

Eleutherosides may activate AMPK, an important “switch” in energy metabolism. AMPK reduces fat storage and increases insulin sensitivity. Through AMPK, eleutherosides may be able to restore insulin signaling in people with diabetes [20, 6, 21, 22].

Heat Shock Protein Activation

Eleuthero may increase heat shock proteins like HSP70 and HSP72. This could help explain its ability to reverse the effects of stress: heat shock proteins protect cells and keep them alive in conditions that would otherwise damage or kill them [23, 24].

Neurotransmitters

Eleuthero extract increases catecholamines (especially dopamine and norepinephrine) in the parts of the brain responsible for managing stress. The exact way it influences their levels and activity is unknown, but this mechanism may underlie eleuthero’s mental health benefits [25, 26, 27].

BDNF Activation

Brain-derived neurotrophic factor, or BDNF, is a protein active in the hippocampus of the brain. It helps nervous tissue grow and reorganize itself, and it protects the brain from damage. Low BDNF is linked to depression and anxiety. Eleuthero increases BDNF in the hippocampus, which could explain its reputation as a brain-boosting supplement [28, 29].

Research connecting eleuthero and BDNF is extremely new. Only two studies have ever tested these effects – one cell study in 2013 and one rat study in 2018 – and while both have shown promising benefits, we cannot yet say that eleuthero will activate BDNF in humans [28, 29].

Sirtuin 3 Activation

Sesamin activates a protein called sirtuin 3, or SIRT3, which regulates energy metabolism and prevents cell death. Through SIRT3, sesamin may protect tissues from inflammation and death after an injury [30, 31, 32].

Eleuthero Safety & Side Effects

Overall, eleuthero is generally regarded as safe.

In mice, it takes an extremely high dose to cause death (over 25 g per kg of body weight). If translated to humans, an average adult would have to eat more than 1.5 kg of dry root for it to be dangerous [33].

Eleuthero has few side effects. Rarely, people taking eleuthero in combination with other herbal supplements may experience sleepiness, cold extremities, increased blood pressure, increased heart rate, or heart palpitations [34, 35, 36].

Children, Pregnancy, and Breastfeeding Mothers

Eleuthero, in combination with other herbs, appears to be safe for children with Familial Mediterranean Fever. Healthy children would probably tolerate eleuthero well, but people should probably avoid giving supplements to children unless a doctor recommends it [37].

The safety of eleuthero for pregnant women is also unclear. Only animal research is available. In lab animals, eleuthero seemed to be protective against birth defects caused by alcohol, but this has never been investigated in humans [38].

Therefore, pregnant and breastfeeding women should avoid eleuthero due to a lack of safety data. If you are pregnant or breastfeeding and want to supplement with eleuthero, it’s important to talk to your doctor first.

Possible Disease Interactions

Dopamine Dysfunction

Eleuthero increases dopamine levels in the brain. People with schizophrenia, which is caused by dysfunctional dopamine signaling, should probably avoid eleuthero [27, 39].

Consult your doctor if you are concerned about the potential side effects and safety of a supplement.

Autoimmunity

Eleuthero has both immune-boosting and anti-inflammatory properties, but its effects on autoimmune disorders are largely unknown. A combination of eleuthero and Andrographis paniculata, called Kan Jang, acts in synergy to suppress autoimmune disease pathways [40].

While this effect may be beneficial in theory, the interaction with drugs used for autoimmune diseases is unknown. If you suffer from an autoimmune disease like lupus, Hashimoto’s or Graves’ disease, talk to your doctor before supplementing with Siberian ginseng.

Eleuthero Drug Interactions

This is not necessarily an exhaustive list of potential interactions between Siberian ginseng and prescription drugs. Talk to your doctor before starting any new supplements to avoid unexpected interactions.

CYP Inhibition

CYPs are liver enzymes that break down drugs and toxins and remove them from the body. Eleutherosides block two of these enzymes, CYP2C9, and CYP2E1; any compound that these enzymes metabolize will take longer to break down and get rid of [41, 42].

CYP2C9

This enzyme breaks down dozens of drugs, including NSAIDs like ibuprofen, diabetes drugs like tolbutamide and glyburide, blood pressure medication like losartan, anticoagulants like warfarin, and many others. Eleuthero can reduce CYP2C9 activity, and therefore may increase the effects of these drugs [43].

CYP2E1

This enzyme breaks down alcohol, some anesthetics, acetaminophen (Tylenol), some industrial toxins, theophylline, chlorzoxazone, and others. Eleuthero can reduce CYP2C9 activity, and therefore may increase the effects of these drugs and toxins [43].

CYP Interactions Summary

Since eleutherosides partially block CYP2C9 and CYP2E1, people taking eleuthero risk building up high blood levels of the following [41, 42, 43]:

• Alcohol
• NSAIDs like ibuprofen
• Diabetes drugs like tolbutamide and glyburide
• Blood pressure medication like losartan
• Anticoagulants like warfarin
• Some anesthetics
• Acetaminophen (Tylenol)
• Some industrial toxins
• Theophylline
• Chlorzoxazone

Note that many of these interactions have not specifically been tested, and are theoretical. Furthermore, this is not an exhaustive list of drugs broken down by CYP2C9 and CYP2E1. Always check with your doctor before supplementing with eleuthero if you are taking any medication.

Other Drugs

Pay especially close attention and consult your doctor before supplementing if you take any of the following:

Digoxin

Digoxin is a drug prescribed to treat problems with heart rhythm. Although reports of this interaction are rare, eleuthero may dangerously increase the effect of digoxin. Some of eleuthero’s active compounds may have similar mechanisms and effects to digoxin; rather than increasing digoxin levels, eleuthero may simply add to its effects. Do not supplement with eleuthero if you are taking digoxin [44, 45].

Hexobarbital

Hexobarbital is a sedative drug. In the 1940s and 1950s, it was widely used to induce anesthesia before surgery. Hexobarbital is quite dangerous and much less common today. Some research suggests that eleuthero could more than double the effect of hexobarbital. If you choose to take eleuthero supplements before any kind of surgery, it is very important to tell your doctor [46, 47].

Lithium and Eleuthero

In a study of Chinese teenagers with bipolar disorder, researchers combined either eleuthero extract or fluoxetine (Prozac) with the teens’ lithium treatment. For a similar degree of benefit, people who took eleuthero with lithium had fewer side effects than those who took fluoxetine with lithium. The mechanism of this combination is unknown [48].

More research is needed to determine if this combination is safe and beneficial. If you’re taking lithium and/or SSRIs, talk to your doctor before supplementing.

Eleuthero & Genetic Predispositions

Eleuthero and its active compounds may increase and decrease the expression of a wide variety of genes. These genes are involved in carbohydrate metabolism, cell-to-cell communication, and small molecule biochemistry [49].

Increased Expression

In a study of human cancer cells exposed to eleuthero extract, the following genes had increased expression [49]:

• Several G-protein-coupled receptors (GPRs) that receive signals from outside of a cell: GPR111, GPR128, GPR 148, and GPRC6A.
• GRM6, which produces metabolic glutamate receptor 6. This protein helps you see in low light; mutations at GRM6 can cause congenital stationary night blindness [50].
• PDE4D, which produces an enzyme that degrades the messenger molecule cAMP. Mutations at PDE4D can increase susceptibility to stroke and cause problems in the bones, brain, and hormones. Note that in healthy people, eleuthero may decrease PDE4D [51, 52].
• PIK3C2G, which produces a protein that regulates cell division. This gene may be involved in type II diabetes [53].
• PLCB1, which produces a protein that helps send and receive signals between brain cells. Mutations at PLCB1 can cause infantile epileptic encephalopathy [54].
• SERPINA1, which produces a protein that blocks certain enzymes in certain parts of the body, including the lungs. Mutations in SERPINA1 can cause lung damage as an enzyme called neutrophil elastase breaks down tiny air sacs called alveoli [55].
• HSPA1B produces a type of heat shock protein that protects cells against damage during periods of stress [56].
• FOXA1 produces a protein called forkhead box A1, which controls the expression of some proteins in the liver [57].

None of these effects have yet been studied in healthy animals or people. These studies only indicate that these genes could be worth studying in people taking eleuthero.

Decreased Expression

In a study of human cancer cells exposed to eleuthero extract, the following genes had decreased expression [49]:

• Several GPRs that receive signals from outside of a cell: GPR17, GPR37, GPR65, GPR101, and GPR112.
• ADCY2, which produces a protein that activates the messenger molecule cAMP [58].
• PLCD4, which produces a phospholipase C enzyme that activates two messenger molecules. PLCD4 is often increased in cancer cells [59].
• CETP, which produces cholesteryl ester transfer protein, which is involved in cholesterol metabolism. This protein transfers molecules from HDL (the “good” cholesterol) to LDL (the “bad” cholesterol). Blocking CETP may reduce bad cholesterol levels in the blood and increase lifespan [60, 61].
• ESR1, which produces one type of estrogen receptor. Estrogen is important for female sexual development and reproduction; however, when estrogen or its receptors are too high, it can cause breast cancer and osteoporosis [62].
• Three of the SERPINB genes: SERPINB2, SERPINB4, and SERPINB9. All of these genes are often expressed in cancer cells and may help cancers survive and grow [63].
• HTR3D, which produces a part of the serotonin receptor 5-HT3 [64].

None of these effects have yet been studied in healthy animals or people. These studies only indicate that these genes could be worth studying in people taking eleuthero.

COMT

Catechol-O-methyltransferase, or COMT, is an enzyme that breaks down dopamine and other catecholamines. People with different levels of COMT activity may respond differently to eleuthero [65].

The COMT gene has an important SNP called V158M (rs4680), which changes the effectiveness of the COMT enzyme. People with two copies of the A allele have the least COMT activity and the highest dopamine; these people belong to the “worrier” type. People with two copies of the G allele have the most COMT activity and the lowest dopamine; these people belong to the “warrior” type. Many people also fall somewhere in the middle of this scale [65].

Eleuthero increases available dopamine in the basal ganglia; this effect may help neutralize the effects of high COMT activity. People with the “warrior” type may possibly benefit more from eleuthero supplements [26].

Familial Mediterranean Fever

Familial Mediterranean Fever, or FMF, is a genetic condition that has been successfully improved with a combination of immune-boosting, anti-inflammatory herbs including eleuthero [37].

People with FMF have a mutation in the MEFV gene. MEFV produces a protein called pyrin, which probably helps control and stop inflammation in healthy people. There are more than 80 different MEFV mutations that cause FMF; the most common is M694V (rs61752717). People with two copies of the G allele at this SNP will develop Familial Mediterranean Fever and may benefit from eleuthero extract [66].

Eleuthero Supplementation & Dosage

Formulations

Eleutherococcus bark, root, leaves, and berries all contain bioactive compounds, but most supplements are derived from the root.

Siberian ginseng root is readily available in capsule and powder form; traditional herbalists also brew a tea from the leaves. Essential oil from Siberian ginseng may have health benefits and prevent mosquito bites, but it is difficult to find.

Eleuthero is often combined with other adaptogenic herbs like rhodiola, ashwagandha, and others. These combinations are not well-studied.

Dosage

There is no standardized dosage for eleuthero because the extract is not standardized and different studies may use different parts of the plant. No sufficiently powered study has been conducted to find a safe and effective dose for any medical purpose.

Most extracts are made from Eleutherococcus root, which is considered very safe to consume [33].

And although megadoses of eleuthero root might not be harmful, this doesn’t mean they’re necessary or desirable.

Based on limited clinical research, people with mild to moderate fatigue may benefit from as little as 2 – 4 g/day, equivalent to 2 – 3 mg of eleutherosides. Other American sources recommend 6 – 12 g of dried root per day, and some Chinese sources recommend 9 – 27 g of dried root per day [67].

Read More

• 11 Eleuthero (Siberian Ginseng) Root Benefits