Ginsenoside Re

Ginsenoside Re at a Glance

Ginsenoside Re is a protopanaxatriol (PPT)-type dammarane saponin and, alongside ginsenoside Rg1, one of the two most abundant PPT ginsenosides in Asian ginseng (Panax ginseng). Where the PPD-type ginsenoside Rb1 is the marquee protopanaxadiol saponin, Re and Rg1 headline the protopanaxatriol side of the family — distinguished by an extra hydroxyl at C-6.

Its most-cited laboratory signal is metabolic: isolated Re lowers blood glucose, improves insulin sensitivity and blunts oxidative stress across rodent models of diabetes, and a parallel line reports cardioprotective, antioxidant activity in stressed heart tissue. That is the reason to care about this particular molecule, and it is developed below in its own section.

Two honest caveats run through everything. First, Re is a large, tri-glycosylated saponin with extremely poor oral bioavailability — well under 1% in animals, and undetectable in the plasma of supplemented humans ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}. Second, and unusually for a ginsenoside, Re has actually been tested as an isolated molecule in a human trial — and that trial was negative ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}. So the metabolic promise is real in cells and rodents but unproven in people, and ginseng’s human glycaemic data belong to the whole extract, not to isolated Re.

Ginsenoside Re & Metabolic Health

This is the section only Re really needs: a distinctive anti-diabetic / insulin-sensitising signal paired with a cardioprotective, antioxidant one — and an unusually direct test of whether either survives in humans.

The preclinical metabolic case is broad. Ginsenoside Re was singled out as the effective component of a Panax ginseng berry extract in obese diabetic ob/ob mice, where treatment normalised glucose and more than doubled insulin-stimulated glucose disposal on a hyperinsulinaemic–euglycaemic clamp ^{1Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →}. In streptozotocin-diabetic rats, isolated Re lowered blood glucose, total cholesterol and triglycerides and restored glutathione and malondialdehyde toward normal in eye and kidney — the first demonstration of Re’s antioxidant efficacy in diabetes ^{3Reference 3Cho WC et al. · 2006AnimalGinsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal modelView study →}. In high-fat-diet mice it improved brain insulin resistance and cognition via the JNK pathway ^{4Reference 4Kim JM et al. · 2017AnimalGinsenoside Re ameliorates brain insulin resistance and cognitive dysfunction in high fat diet-induced C57BL/6 mice — animal modelView study →}, and a serum/urine metabolomics study traced its glucose-lowering to CB1 → CaMKKβ → AMPK activation with increased insulin secretion ^{5Reference 5Wang H et al. · 2021AnimalUHPLC-MS-based serum and urine metabolomics reveals the anti-diabetic mechanism of ginsenoside Re in type 2 diabetic rats — animal modelView study →}.

The cardiovascular signal is separate but consistent. Isolated Re protected cardiomyocytes from hypoxia/reoxygenation injury by stabilising HIF-1α (blocking its VHL-mediated ubiquitination) ^{6Reference 6Sun H et al. · 2020In vitroGinsenoside Re treatment attenuates myocardial hypoxia/reoxygenation injury by inhibiting HIF-1α ubiquitination — in vitroView study →}, and attenuated isoproterenol-induced myocardial injury in rats by driving the Nrf2 → glutathione antioxidant axis ^{7Reference 7Wang QW et al. · 2018AnimalGinsenoside Re attenuates isoproterenol-induced myocardial injury in rats — animal modelView study →}. The through-line with the diabetic work is antioxidant defence.

Then the reality check. In a randomised controlled trial, overweight/obese adults with impaired glucose tolerance or new type-2 diabetes took ginsenoside Re 250–500 mg/day (or ginseng extract) for 30 days, assessed by clamp and disposition index — and saw no improvement in insulin sensitivity or β-cell function ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}. The authors pinned the null result on poor systemic bioavailability, consistent with pharmacokinetic work that could not detect Re in the plasma of supplemented obese adults at all ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}. Re is a genuinely interesting metabolic molecule in a dish and in a mouse; the isolate has not delivered in the one place it was directly tried in people.

What It's Used For

The evidence divides cleanly: a broad preclinical metabolic and cardioprotective literature on isolated Re, against a single negative human isolate trial and near-zero oral exposure.

Best-developed (preclinical):anti-diabetic / insulin-sensitising activity — isolated Re lowers glucose and lipids, improves insulin-stimulated glucose disposal and eases oxidative stress across rodent diabetes models ^{1,3,4,5Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →Reference 3Cho WC et al. · 2006AnimalGinsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal modelView study →Reference 4Kim JM et al. · 2017AnimalGinsenoside Re ameliorates brain insulin resistance and cognitive dysfunction in high fat diet-induced C57BL/6 mice — animal modelView study →Reference 5Wang H et al. · 2021AnimalUHPLC-MS-based serum and urine metabolomics reveals the anti-diabetic mechanism of ginsenoside Re in type 2 diabetic rats — animal modelView study →}.

Emerging, worth watching:a coherent cardioprotective, antioxidant story — isolated Re protects heart tissue via HIF-1α stabilisation and the Nrf2/glutathione axis in cells and rats ^{6,7Reference 6Sun H et al. · 2020In vitroGinsenoside Re treatment attenuates myocardial hypoxia/reoxygenation injury by inhibiting HIF-1α ubiquitination — in vitroView study →Reference 7Wang QW et al. · 2018AnimalGinsenoside Re attenuates isoproterenol-induced myocardial injury in rats — animal modelView study →}.

The rare human data cut against the isolate:the one RCT of isolated Re (250–500 mg/day) showed no improvement in insulin sensitivity or β-cell function in people with impaired glucose tolerance/diabetes ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}.

The load-bearing caveat:oral bioavailability is ~0.2% in mice and Re is undetectable in supplemented human plasma; it is deglycosylated by gut bacteria toward Rh1/F1/Rg2 (the PPT route — not compound K), so intact-Re dosing delivers almost no parent molecule to tissue ^{8,9Reference 8Peng D et al. · 2012ReviewGinsenoside Re: its chemistry, metabolism and pharmacokinetics — reviewView study →Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume, tempered for isolate-vs-plant match and bioavailability. A beta, not a validated metric. Rows rest on isolated Re in rodents or cells; the one human isolate trial (glycaemic) was negative, and near-zero oral exposure caps every score. Each application links to its write-up.

Mechanisms

Target / pathway	Effect	Relevant to
CB1 → CaMKKβ → AMPK activation	↑ insulin secretion; ↓ glucose and lipids	glycaemic control
Insulin-stimulated glucose disposal (clamp)	↑ peripheral glucose uptake	glycaemic control
Glutathione ↑ / malondialdehyde ↓	reduced oxidative stress in eye, kidney, heart	glycaemic (vascular)cardioprotection
Nrf2 → GCLC / GCLM	↑ glutathione synthesis	cardioprotection
HIF-1α (blocks VHL-mediated ubiquitination)	stabilises HIF-1α; preserves cardiomyocyte viability under hypoxia	cardioprotection
JNK pathway; cholinergic protection	improved brain insulin signalling and cognition	brain insulin resistance
Gut microbiota (β-glucosidases)	deglycosylation Re → Rh1 / F1 (PPT route, not compound K)	pharmacokinetics; bioactivation

Pharmacokinetics

Near-total non-absorption is the load-bearing fact — and it is worse for Re than for its siblings. As a large, tri-glycosylated PPT saponin, Re crosses the gut wall very poorly: absolute oral bioavailability was 0.19–0.28% in mice at 10–50 mg/kg ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}. Absorption of what little enters is fast but clearance is rapid — the reported human half-life after a 200 mg oral Re tablet is only about 1.8 hours ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}. Critically, Re is deglycosylated by intestinal bacteria before absorption, stripped stepwise mainly to Rh1 and F1 (and onward toward Rg2 and the protopanaxatriol aglycone) — the PPT metabolic route, structurally distinct from the PPD route that yields compound K from Rb1 ^{8Reference 8Peng D et al. · 2012ReviewGinsenoside Re: its chemistry, metabolism and pharmacokinetics — reviewView study →}. The practical endpoint is stark: pharmacokinetic work could not detect Re in the plasma of supplemented obese adults at all ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}, which is exactly why the isolated-Re human metabolic trial was negative ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}. Cell-study pharmacology of intact Re is not what an oral dose achieves in a person.

Clinical Trials

Unusually for a ginsenoside, isolated Re has been trialled in humans — and the result was null. A randomised controlled trial gave ginsenoside Re (250–500 mg/day) or ginseng extract for 30 days to overweight/obese adults with impaired glucose tolerance or new type-2 diabetes and found no improvement in insulin sensitivity or β-cell function ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}. Otherwise the literature is preclinical, and any positive human ginseng signal is whole-extract, not attributable to Re.

Completed	Planned	Terminated	Preclinical
1human RCT (isolated Re + ginseng extract) — negative ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}	None identified	None	Extensive

Last checked: July 2026.

Isolate vs. Plant Studies

Re sits in an interesting spot on the isolate-vs-plant axis. Much of the metabolic literature genuinely isolates the molecule — Re was pulled out of a ginseng berry extract and identified as the effective anti-diabetic component in ob/ob mice ^{1Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →}, and the streptozotocin-rat, high-fat-diet-mouse and metabolomics studies all dose purified Re ^{3,4,5Reference 3Cho WC et al. · 2006AnimalGinsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal modelView study →Reference 4Kim JM et al. · 2017AnimalGinsenoside Re ameliorates brain insulin resistance and cognitive dysfunction in high fat diet-induced C57BL/6 mice — animal modelView study →Reference 5Wang H et al. · 2021AnimalUHPLC-MS-based serum and urine metabolomics reveals the anti-diabetic mechanism of ginsenoside Re in type 2 diabetic rats — animal modelView study →}, as do the cardioprotection studies ^{6,7Reference 6Sun H et al. · 2020In vitroGinsenoside Re treatment attenuates myocardial hypoxia/reoxygenation injury by inhibiting HIF-1α ubiquitination — in vitroView study →Reference 7Wang QW et al. · 2018AnimalGinsenoside Re attenuates isoproterenol-induced myocardial injury in rats — animal modelView study →}. That is a strength: the rodent signal is Re-specific, not an inference from “ginseng.”

The weakness is where it counts. The one human study of the isolate was negative ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}, and Re’s ~0.2% oral bioavailability and undetectable human plasma levels ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →} mean the rodent doses simply are not reachable orally in people. So while the preclinical evidence is honestly about Re, the human evidence for ginseng’s glycaemic and tonic effects remains whole-extract — where Re is one of many saponins and its individual contribution is unquantified.

Prevalence in Nature

Ginsenoside Re is one of the major protopanaxatriol saponins of Panax species, sitting at roughly 0.15% of dried P. ginseng root and, with Rg1, anchoring the PPT side of the ginsenoside profile ^{10Reference 10Cai J et al. · 2022ReviewA comprehensive system review of pharmacological effects and relative mechanisms of ginsenoside Re: recent advances and future perspectives — reviewView study →}. Its distribution across the plant is notable: Re is unusually enriched in the berry, flower bud and leaf relative to the root — the berry extract in which its anti-diabetic activity was first isolated is a case in point ^{1Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →}. It also occurs in American ginseng (P. quinquefolius) and notoginseng (P. notoginseng), and belongs to the same PPT group as Rg1, Rg2, Rf and Rh1 ^{10Reference 10Cai J et al. · 2022ReviewA comprehensive system review of pharmacological effects and relative mechanisms of ginsenoside Re: recent advances and future perspectives — reviewView study →}.

Because content varies with species, plant part, root age, cultivar and processing (red vs. white), the single root figure above is a representative order of magnitude rather than a fixed value; the berry/flower/leaf enrichment and the American/notoginseng levels are described qualitatively here and tracked as open figures in this compound’s gaps note.

Discovery & Synthesis

Ginsenoside Re was characterised among the ginsenosides isolated and named by Shibata, Tanaka and colleagues in Japan in the late 1960s–early 1970s, when the Panax ginseng saponins were separated and lettered by thin-layer-chromatography mobility (the “R” saponins, ordered a→h by decreasing polarity). Re is one of the more polar members — a tri-glycosylated PPT saponin — which is exactly what makes it so poorly absorbed.

There is no commercially important total synthesis: like the other ginsenosides, Re is obtained by extraction from ginseng root, berry, leaf or flower, and is a common starting material for enzymatic biotransformation into rarer, more absorbable minor ginsenosides (e.g. transrhamnosylation and controlled deglycosylation toward Rg2/Rh1-type products). Manufacture today is therefore an isolation-and-conversion story, not a synthetic one.

Patents: not yet researched.

Toxicity & Safety

Isolated ginsenoside Re carries a low toxicity flag. Its own pharmacology is antioxidant and glucose-lowering rather than cytotoxic, and its near-total lack of oral absorption keeps systemic exposure minimal ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}, further limiting any chance of reaching harmful levels from oral intake. The 30-day human trial at up to 500 mg/day reported no safety signal beyond the (absent) efficacy ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}.

The practical cautions attach less to the isolate than to context. Re’s most reproducible action is glucose-lowering, so the theoretical concern is additive hypoglycaemia alongside anti-diabetic drugs or insulin — a whole-ginseng caution that applies in principle to a glucose-active saponin ^{1,3Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →Reference 3Cho WC et al. · 2006AnimalGinsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal modelView study →}. No dedicated human drug-interaction studies of isolated Re (CYP isoforms, P-glycoprotein) have been characterised, and the general ginseng cautions (stimulation, anticoagulant/antiplatelet interactions) are the practical reference point, not isolate data. Reproductive/developmental toxicity of isolated Re is not characterised here; pregnancy and lactation decisions belong to the herb or product page where intake is decided.

Safety at a Glance

Low / no toxicity

Low intrinsic toxicity, minimal oral exposure. Antioxidant/glucose-active saponin that is barely absorbed by mouth; a 30-day 500 mg/day human trial flagged no safety problem.
Additive glucose-lowering (theoretical). Re’s most consistent action is hypoglycaemic — relevant alongside anti-diabetic medication or insulin, chiefly as a whole-ginseng caution.
Interactions not formally studied for the isolate. No dedicated CYP/P-gp interaction data for isolated Re; default to whole-ginseng cautions (stimulation, anticoagulant/antiplatelet).
Isolate ≠ extract. Re’s near-zero bioavailability means oral isolate behaves very differently from a standardised whole-ginseng extract; do not read rodent-dose effects as human effects.

Dosage

There is no established human dose of isolated ginsenoside Re. The only human trial used 250–500 mg/day for 30 days and found no metabolic benefit ^{2Reference 2Reeds DN et al. · 2011RCTGinseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trialView study →}, and Re is essentially unabsorbed orally ^{9Reference 9Gao XY et al. · 2022ReviewPharmacological properties of ginsenoside Re — reviewView study →}, so a milligram figure does not map onto delivered exposure. Preclinical efficacy figures come from rodents — anti-diabetic and cardioprotective studies dose in the low milligrams-per-kilogram range by gavage or injection, chosen for the experiment rather than validated for people ^{1,3,7Reference 1Attele AS et al. · 2002AnimalAntidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal modelView study →Reference 3Cho WC et al. · 2006AnimalGinsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal modelView study →Reference 7Wang QW et al. · 2018AnimalGinsenoside Re attenuates isoproterenol-induced myocardial injury in rats — animal modelView study →}. In practice, human intake of Re happens through standardised whole-ginseng extracts (root, and increasingly berry/leaf preparations that are richer in Re), where it is one of many saponins and its individual contribution is unknown.

These are doses studied in research and are not a personal recommendation.

References

Attele AS, Zhou YP, Xie JT, et al. (2002). Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component (ginsenoside Re) — animal model. Diabetes, 51(6), 1851–1858. https://pubmed.ncbi.nlm.nih.gov/12031973/
Reeds DN, Patterson BW, Okunade A, et al. (2011). Ginseng and ginsenoside Re do not improve β-cell function or insulin sensitivity in overweight and obese subjects with impaired glucose tolerance or diabetes — randomized controlled trial. Diabetes Care, 34(5), 1071–1076. https://pubmed.ncbi.nlm.nih.gov/21411505/
Cho WC, Chung WS, Lee SK, et al. (2006). Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats — animal model. European Journal of Pharmacology, 550(1–3), 173–179. https://pubmed.ncbi.nlm.nih.gov/17027742/
Kim JM, Park CH, Park SK, et al. (2017). Ginsenoside Re ameliorates brain insulin resistance and cognitive dysfunction in high fat diet-induced C57BL/6 mice — animal model. Journal of Agricultural and Food Chemistry, 65(13), 2719–2729. https://pubmed.ncbi.nlm.nih.gov/28314104/
Wang H, Teng Y, Li S, et al. (2021). UHPLC-MS-based serum and urine metabolomics reveals the anti-diabetic mechanism of ginsenoside Re in type 2 diabetic rats — animal model. Molecules, 26(21), 6657. https://pubmed.ncbi.nlm.nih.gov/34771066/
Sun H, Ling S, Zhao D, et al. (2020). Ginsenoside Re treatment attenuates myocardial hypoxia/reoxygenation injury by inhibiting HIF-1α ubiquitination — in vitro. Frontiers in Pharmacology, 11, 532041. https://pubmed.ncbi.nlm.nih.gov/33013381/
Wang QW, Yu XF, Xu HL, et al. (2018). Ginsenoside Re attenuates isoproterenol-induced myocardial injury in rats — animal model. Evidence-Based Complementary and Alternative Medicine, 2018, 8637134. https://pubmed.ncbi.nlm.nih.gov/29849732/
Peng D, Wang H, Qu C, et al. (2012). Ginsenoside Re: its chemistry, metabolism and pharmacokinetics — review. Chinese Medicine, 7, 2. https://pubmed.ncbi.nlm.nih.gov/22314249/
Gao XY, Liu GC, Zhang JX, et al. (2022). Pharmacological properties of ginsenoside Re — review. Frontiers in Pharmacology, 13, 754191. https://pubmed.ncbi.nlm.nih.gov/35462899/
Cai J, Huang K, Han S, et al. (2022). A comprehensive system review of pharmacological effects and relative mechanisms of ginsenoside Re: recent advances and future perspectives — review. Phytomedicine, 102, 154119. https://pubmed.ncbi.nlm.nih.gov/35617888/