Disclaimer: We do not provide medical advice. We simply provide the available information from scientific journals. Consult your health practitioner. Please NEVER take ginseng in place of traditional healthcare plans.

Ginseng: Benefits, Side effects and Buyers Guide

Written on February 20, 2022

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Overview

Ginseng comes in many forms, so how do you know which one to buy? Purchasing ginseng can be difficult, and at times manufacturers make claims that are often unscientific and lacking in evidence.

In this article we explain what traits to look for when purchasing ginseng so you can make the best decision based on the evidence available.

We identify Panax Ginseng as the best overall form of ginseng, due to the high level of ginsenosides – however there are many different forms of panax ginseng. Ginsensosides are the active ingredients in ginseng and there are over 50 types.

Ginsenosides are involved in many chemical reactions in your body that can improve your health.

They are anti-inflammatory, anti-cancer and preserve your health through a variety of mechanisms and pathways.

In this article, we examine the beneficial effects of ginseng, and the specific benefits of certain ginsenosides.

Ginseng: Advantages and Limitations

What it is

Ginseng is a herb that comes in a variety of types, each with slightly varied health benefits.

Fresh ginseng refers to those harvested before 4 years. However most ginseng is harvested after 4 or more years, with red ginseng being farmed up to 14 years after it is planted.

In this article, we refer to ginseng studies that mostly examine Panax ginseng, as it is the most promising for certain health benefits.

Where this is not the case, we refer to it as their scientific name. For example American ginseng is known as Panax quinquefolius and korean ginseng is C A Meyer ginseng.

How it works

To understand how Ginseng works, we need to discuss their active ingredient known as ginsenosides.

There are numerous types of ginsenosides and they vary in terms of their impact on your health.

Ginsenosides can be first classified into diol-type or triol-type [1]. This means that their chemical structure is different. Put simply, diol-type ginsenosides have two bonds, and triol-types have three. This affects how they work.

Ginsenosides appear to exert anti-inflammatory activity through suppressing the production of pro-inflammatory cytokines [2].

Common ginsenosides and their metabolites/derivatives include ginsenoside (g)-Rb1, compound K, G-Rb2, G-Rd, G-Re, Rg3, Rg5, Rh1, Rh2 and Rp1.

A study examining individual differences in ginsenoside pharmacokinetics in healthy volunteers found that bioconverted red ginseng extract led to a higher expression of Rg3, Rk1 + Rg5, F2 and CK.

A development of a sensitive method for detecting 13 ginsenosides including Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K (CK), protopanaxadiol (PPD), and protopanaxatriol (PPT) was performed [3]. This experiment was performed in human plasma. However, Ck, Rh2, PPd and PPT ginsenosides were also present despite not being present in red ginseng extract suggesting that certain ginsenosides are generated via human metabolism.

What are ginseng saponins?

Ginseng saponins is another term for ginsenosides.

Benefits

1. Possibly reduces body fat mass gain

Korean Ginseng can reduce body weight [4].

More importantly, the body weight loss was in the form of fat. Ginseng also prevented the accumulation of fat in the body when undergoing a caloric surplus.

This suggests that ginseng can improve body composition and general health.

How:

Your body contains a hormone (adiponectin) that regulates fat burning in the body. Higher levels of adiponectin are present in people with low body-fat and the opposite is true in those with high body-fat [5].

Ginseng boosts adiponectin secretion in fat cells resulting in the upregulating of fat oxidation and glucose metabolism [6][7][8][9][10]. These studies also indicate that green tea has similar effects on boosting adiponectin and can lower bodyfat. Insulin sensitivity increases in response to increased adiponectin.

Another hormone, resistin is also affected by ginseng supplementation.

Resistin levels rise in proportion to body fat and decline with decreased body fat [11]. The ginsenosides (Rc and Re) have been shown to reduce resistin levels in cells [12][13].

Rb1 ginsenoside has been shown to increase adiponectin signalling [14][15].

2. Can improve your gap junction health

Gap junctions are what allow communication to occur between the cells.

Gap junction health is thought to be an associated cause of many diseases ranging from atherosclerosis, diabetes and hypertension to neurological disorders [16][17].

In the heart, gap junction protein expression is associated with the prevalence of serious cardiac issues [18][19].

Ginseng is thought to benefit gap junction health, and this is what results in the subsequent health improvements.

Gap junction health is also associated with the prevalence of neurological disease [20].

And glial communication and nerve communication occurs through gap junctions which amplifies inflammation and neurodegeneration.

Understanding how gap junctions work can provide us with new therapeutic strategies for neurodegeneration, including ginseng.

Korean Ginseng may induce certain benefits for health through a positive effect on gap junction health.

3. May help prevent heart disease symptoms

By lowering the oxidative damage to membrane lipids and proteins, Korean Ginseng may help prevent heart issues and associated symptoms.

A systematic review indicates that ginsenosides found in ginseng may improve blood flow, blood pressure and lower the risk of myocardial infarction and heart disease [21].

Gap junction issues can lead to increased risk of heart disease, and ginseng possibly lowers these risks by acting upon gap junctions [22][23].

Along with heart issues, gap junction alterations have been observed to result in hyperproliferative skin disorders, lymph disease, inflammatory lung disease, liver injury and abnormal cell growth.

Studies suggest that specific ginsenosides have different roles in ameliorating disease [24].

Specific ginsenosides impact Gap junctions intracellular communication (GJIC) including:

Rc, Rb3, Rd2, Rh2, Fe, Ra1, Re, Rg2 (ROr), la, Rh1, Rh1 (20R), F1, protopanaxtriol, panaxatriolm, Rg1, chikusetsaponin-L8 induced GJIC reductions
Ginsenoside-R0 , Ginsenoside- Rd, ginsenoside-Rg3 protect against vanadate induced GJIC reduction
oleanolic acid, Rb2, Rd, ginsenoside-Rg2 inhibited the cytokine IL-1alpha induced reduction in gap junction intracellular communication
no compounds protected against protein kinase C activator TPA -induced GJIC inhibition

GJIC reductions induced by Rb3, Rd2, notoginsenoside-Fe, ginsenoside-Rh1 (20S), ginsenoside-Rh1 (20R), ginsenosude-F1, panaxatriol and ginsenoside-Rg1 were inhibited by tyrosine kinase (TK) inhibitor genistein, while GJIC reductions induced by ginsenoside-Rb3, ginsenoside-Rd2, Ra1, Rg2 (20R), ginsenoside-la were attenuated in the presence of the PKC inhibitorcalphostin C.

GJIC reductions induced by ginsenoside-Rc, protopanaxatriol were not inhibited by genistein or by calphostin C.

Those that do not obviously affect GJIC: oleanolic acid, R0, Rb1, Rb2, Rd, Rg3, panaxadial, R4, Rg2 (20s), Rf, F3,

In the future, it may be possible to select for ginsenosides in order to produce the desired result.

4. Possibly protects your brain from dementia

A study found that the Rg1 ginsenoside protects against cognitive impairment and hippocampal cell apoptosis in experimental vascular dementia [25].

This study was performed on mice, however it indicates that a single ginsenoside (Rg1) can prevent brain cell loss.

The ginsenoside Rg1 promoted GPR30 levels and protected against cognitive decline, and also prevented memory loss.

5. Protects against cerebral ischaemia

Certain ginsenosides may confer specific benefits, as one study examined the effects of Rg1, Rb1, Rh2, Rg3, Rg5 and Re on cerebral ischemia recovery [26].

The role of ginsenosides Rb1 and Rg3 on cerebral ischemia was significantly more than control group, and the highest among all the ginsenosides [27].

How:

The neuroprotective mechanism is twofold, through inhibiting the expression of IL-1B, TNF-a and IL-6, and by upregulating TLR/MyD88 and SIRT1 activation signalling.

In plain english, this means that ginseng works in two different ways; by reducing the expression of harmful cytokins and increasing the concentration of proteins SIRT1 and TLR.

It was found Rg1, Rh2, Re and Rg5 were effective in reducing oxidative stress, apoptosis and cognitive dysfunction, but to a lesser extent than Rb1 and Rg3.

6. Maintain microglia health

The microglia are immune cells that reside in the central nervous system (CNS) and perform multiple roles.

They protect you from foreign antigens and clear your immune system of debris to maintain your health[28][29][30].

After injury to the CNS, activated microglia guide stem-cells during recovery and neurogenesis [31][32]. Ginseng appears to help maintain microglial health which has secondary benefits for you mentally and physically.

Microglia maintain CNS homeostasis however overactivation can lead to an accumulation that results in disease.

The overabundance of activated microglia is associated with neurological trauma, inflammation and numerous brain disorders.

Activated microglia release an abundance of glutamate which results in glutamate induced cell death that can occur in the brain [33].

Therefore it appears blocking microglia can reduce the incidence of neurotoxicity and disease, however this is not always the case as microglia can also exert beneficial effects on the brain by producing neurotrophic factors [34][35][36][37][38]. Glutamate blockers can have hugely adverse effects, suggesting that glutamate overactivation is worse than too little activation [39].

Ginseng can help maintain an optimal balance of microglia, specifically in the event of head trauma.

7. May have Anticancer effects

Defects in gap junction communication results in impaired cell homeostasis and may lead to increased risk of cancer [40].

Antitumor mechanism of ginsenosides Rg3

Ginsenoside Rg3 is a steroid glycoside that regulates many signaling pathways [41].

Ginsenoside Rg3 plays an important role in the prevention of cancer through various mechanisms.

The suggested mechanisms involve increasing cancer apoptosis, the inhibition of proliferation, metastasis and angiogenesis, as well as the promotion of immunity.

Ginsenoside Rg3 can be used to improve chemotherapy efficacy and/or reduce adverse effects via various mechanisms.

Ginsenoside Rg3 can be a natural medicine against cancer, however more research is required.

Preliminary studies suggest that Rg3 can exert significant functions in preventing various cancers.

A review found that ginsenoside Rg3 led to an improvement of antioxidant and anti-inflammation properties, immune regulation, increase in tumor apoptosis, prevention of tumor invasion and metastasis, tumor proliferation and angiogenesis, and reduction of chemoresistance and radioresistance.

One clinical study examined the inhibitory effect on lung metastasis of two Red ginseng preparations by two tumor cells classified as highly metastatic [42].

These were B16-Bl6 melanoma and colon 26-M3.1 carcinoma in mice.

The first formulation contained 20(R) and 20(S) ginsenoside-Rg3, and the other Rb2.

Results observed:

In vitro, there was found significant inhibition of adhesion to fibronectin and laminin by B16-BL6 melanoma. The inhibition was Dose dependent.

In vivo, consecutive administration of 100 mcg/mouse of 20(r) or 20(s)-Rg3 1,2,3,4 days after tumor inoculation led to inhibition of lung metastasis.

Intravenous administration of both saponins (100-1000 mcg/mouse) induced a significant decrease in lung metastasis of B16-Bl6 melanoma.

Both saponins were effective at inhibiting lung metastasis created by colon 26-M3.1 carcinoma.

When 20(r) or 20(s) Rg3 was orally administered consecutively after tumor inoculation in a spontaneous model using B16-Bl6 melanoma, both inhibited lung metastasis.

These findings suggest that ginseng saponins, Rg3 (20 R and 20 S) possess the power to inhibit metastasis of lung tumor cells and the mechanism of action is related to anti-angiogenesis, inhibition of tumor cell adhesion and invasion.

This suggests Ginsenoside Rg3 has anti tumor effects on Lewis lung carcinoma and B16 melanoma by inhibiting tumor cell invasion and metastasis [43].

It also reduces the growth of intestinal cancer and inhibits cell proliteration.

A note on endothelial cells

Endothelial progenitor cells affect the growth of early tumors as they intervene in the angiogenic switch promoting tumor neovessel formation. When Ginsenoside Rg3 was applied to cultured Endothelial progenitor cells (EPC) it resulted in decreased cell migration, cell proliferation and formation of EPCs. Crucially, Rg3 reduced the phosphorylation cascade of the VEGF dependent p38/ERK. A transplant mice (xenograft) tumor model clearly showed Rg3 to suppress tumor angiogenesis by inhibiting the mobilization of EPCs from the bone marrow to the blood circulation. It also modulated VEGF-dependent tumor angiogenesis. As a potential therapeautic, Rg3 works to inhibit EPC activity leading to an anticancer effect [44].

Ginsenoside Rg3 is a prodrug that due to its anti-angiogenic properties, can starve tumors of energy [45].

How does Rg3 work?

The stereospecific effects of ginsenoside 20-Rg3 inhibits TFG-Beta1-induced EMT [46].

Specifically, it is 20(R)-Rg3 that increases expression of E-cadherin and repressed expression of the mesenchymal marker vimentin during initiation of the TFG-B1-induced EMT NOT Rg3-20S. This is evidence that 20(r)-Rg3 suppresses lung cancer migration, invasion and anoikis resistance (in vitro) by inhibiting the TGF-B1-induced transition [47].

Anticancer effects and potential mechanisms of ginsenoside Rh2

G-Rh2 exhibits anticancer activity in vitro and in vivo by modulating several signaling pathways, including Phosphatidylinositol 3-kinase, protein kinase B, mammalian target of rapamycin and PDZ-binding amongst others [48].

G-Rh2 can be used in conjunction with chemotherapy to faciliate treatment [49].

Pancreatic cancer

For pancreatic cancer first line Gemcitabine is the best current treatment. However after a few months, Gemcitabine resistance leads to ineffective treatment.

The ginsenoside Rg3 inhibited the viability of Gemcitabine-resistant pancreatic cancer cells through apoptosis [50].

Ginsenoside Rg3 may have potential to be an effective anticancer agent for chemoresistant pancreatic cancer [50].

It is unclear how Ginsenoside Rg3, type R and type S work, however they appear to be different in their effectiveness for treating cancerous cells [51].

It was demonstrated through high performance liquid chromatography assay, PCR and reverse PCR that 20S-ginsenoside resulted increased inhibition of cell growth, compared with treatment with 20R Rg3 in the human HepG2 hepatocarcinoma.

It was further found that it was 20S-Rg3 reduced global genomic DNA methylation, altered cystosine methylation of the promoter regions of P53, B cell lymphoma 2 and vascular endothelial growth factor – more than treatment with 20R Rg3 in HepG2.

Side effects

Consult your medical provider prior to any supplement regime. This list of side effects is not comprehensive.

Side effects of ginseng are rare however can include:

rash
liver damage
allergic reactions
insomnia
diarrhea
high blood pressure
anxiety
vomiting

Ginseng can interact with certain medications including:

caffeine
insulin (ginseng decreases blood sugar)
depression MAOIs leading to headache and insomnia, anxiousness
diabetes medications
immunosuppressants
midazolam
selegiline
fexofenadine (allegra)
kaletra, ritonavir, lopanavir
raltegravir, isentress
imantinib, gleevec
nifedipine, procardia

Buyers Guide

Ginseng quality is determined by ginsenoside content. And ginsenoside content varies according to growing conditions, age, harvest time and processing method.

Of these variables, consumers should determine harvest time and processing. There are also other factors including whether the root or hair is used.

Root vs Hair

The root and root-hair contain most of the ginsenoside content with less content in the stem. Gradual increases concentrations in the root and root-hair occur from one to five years. After five years, ginsenoside concentration detected in leaves falls [52]. This indicates that the root and root-hair concentrations increase with age. Therefore, higher age is preferred as most of ginsenosides are found in the root, and concentrations increase over time.

Higher age does appear to be generally more beneficial for health [53].

Nowadays ginseng is predominantly farmed, and there is limited evidence as to whether wild ginseng contains higher concentrations of ginsenosides.

Harvest Age

The harvest age affects the ratio of ginsenosides [54]. For example, the ratio of ginsenoside Ro to Re changes depending on age of the ginseng. Ro/Re ratio was highest in ginseng aged 5-6 years and lower in ginseng aged 2-3 years.

Furthermore, ginseng harvest season affects the ratio of ginsenosides Re to Rg1. In May and June, Re was detected at higher levels than Rg1. Rg1 content was higher from August to October.

Drying Method

Drying method is also an important factor in preserving ginsenoside content. Vacuum freeze drying preserved ginsenoside content at a higher percentage than normal air-drying [55].

As a result, therapeautic benefits and effects are significantly affected by the timing of ginseng harvest. These manufacturing variables should be controlled to achieve specific health effects.

New Zealand Ginseng

New Zealand grown Ginseng appears to have a higher concentration of ginsenosides compared to Chinese or Korean grown counterparts [56].

As NZ ginseng is rare, korean ginseng is superior to other forms (look for C.A. Meyer).

Dosage

Consult your medical provider prior to any supplement regime. This list of side effects is not comprehensive.

Pregnant women, children, auto-immune disease sufferers, insomniacs should avoid ginseng.

Dosages (safe) range from 200mg – 3g per day.

Higher doses may lead to side effects including nausea, dizziness, vomitting and allergic reactions.

The Bottom Line

As a promising compound, ginseng has moderate evidence.

Ginseng has been used for centuries in Chinese medicine. In recent times, western adoption has been rising due to the scientific evidence.

Ginsenosides may improve gap junction health and microglia expression both of which have been implicated in serious health conditions.

Ginseng type determines the efficacy of the product. We suggest Korean or New Zealand ginseng as they contain active ingredients in higher concentration.

Anecdotally, ginseng appears to improve energy and mood. The evidence suggests that this may be due to the strong anti-oxidant force of ginseng.

Appendix:

1. Processing affects absorption and bioavailability of ginsenosides [57]

When you pay for a ginseng supplement, understand that strict processing is required to ensure product consistency and quality. It’s really difficult to control for ginsenoside content given many factors affect levels. The best products isolate ginsenosides using ideal processing to produce a superior product.

2. Ratios of ginsenosides change during processing – panax quinquefolium vs panax

https://pubmed.ncbi.nlm.nih.gov/18718179/ – super interesting one relating to the specific effects of ginsenosides. Possibly not scientific. Rg1 appears stimulating (found in Panax ginseng) whereas Rb1 calms. When Ginsenoside Rh2, an antitumor agent undergoes steaming it can increase Rb1.

3. Korean Panax ginseng C A Meyer improves brain function, enhanced immune system function, enhanced liver function

The number of ginsenosides contained in Korean panax ginseng is 38 ginsenosides, which is substantially more than American ginseng (19 ginsenosides) [58]. Korean ginseng has been shown to contain more polyethylene, acid polysaccharaides, phenol compounds and main non-sapnonins than American and Sanchi ginseng.