The Immortality Herb: Blood Sugar, Cholesterol, and Cellular Energy

How jiaogulan activates the AMPK energy pathway to improve blood sugar, lipids, and endurance — with clinical trial evidence

Jiaogulan (Gynostemma pentaphyllum) is a climbing vine from the cucumber family, traditionally brewed as a tea in southern China and Vietnam where locals in some regions drink it daily into old age — earning it the nickname "immortality herb." Modern research has found a compelling biochemical reason behind this reputation: its active compounds, called gypenosides, activate AMPK, the cellular enzyme that regulates energy metabolism and is targeted by both berberine and metformin. A randomized controlled trial in drug-naive type 2 diabetic patients showed jiaogulan tea reduced fasting plasma glucose by 3.0 mmol/L and HbA1c by approximately 2 percentage points over 12 weeks, compared to minimal change in the placebo group [1]. A systematic review of 22 randomized controlled trials found significant improvements in triglycerides, LDL cholesterol, and total cholesterol in people with dyslipidemia [3].

Gypenosides: More Than 200 Active Compounds

Jiaogulan's leaves contain over 230 isolated compounds, of which approximately 189 are saponins called gypenosides [5]. These saponins bear a structural resemblance to ginsenosides — the active compounds in ginseng — which is why jiaogulan is sometimes called "southern ginseng." However, jiaogulan contains far more distinct saponin structures than ginseng. Among the most studied are damulin A and damulin B, two novel dammarane-type gypenosides that were isolated specifically for their AMPK-activating properties.

Gypenosides also include flavonoids, polysaccharides, and chlorophyll derivatives that contribute antioxidant, anti-inflammatory, and prebiotic activity. The leaves are typically prepared as a tea (dried and steeped) or as a standardized extract in capsule form.

How AMPK Activation Works

AMPK (AMP-activated protein kinase) functions as the body's cellular energy sensor. When intracellular energy is low — during exercise, caloric restriction, or certain metabolic stressors — AMPK switches on pathways that increase glucose uptake into cells, stimulate fat oxidation, improve mitochondrial biogenesis, and suppress energy-wasting processes. This is the same mechanism activated by metformin (the most widely prescribed diabetes drug), berberine, and fasting.

Gypenosides activate AMPK directly in muscle and liver tissue. In cell studies, damulin A and B increased GLUT4 translocation to the plasma membrane — meaning more glucose transporter proteins move to the cell surface, pulling glucose out of the bloodstream more effectively. They also increased beta-oxidation (fat burning) in muscle cells.

The result of AMPK activation in the context of blood sugar: lower fasting glucose, improved insulin sensitivity, and reduced HbA1c. In the context of lipids: reduced triglyceride synthesis, lower LDL, and upregulation of LDL receptor expression.

Blood Sugar and Insulin Sensitivity

The human clinical evidence comes primarily from a series of trials conducted by Huyen and colleagues in Vietnam, testing jiaogulan tea in drug-naive type 2 diabetic patients.

The 2010 trial (PMID 20213586) randomized 24 patients to either 6 g/day of authenticated jiaogulan tea or placebo tea for 12 weeks [1]. The jiaogulan group saw fasting plasma glucose fall by 3.0 ± 1.8 mmol/L, compared to 0.6 ± 2.2 mmol/L in the placebo group (p<0.01). HbA1c dropped approximately 2 percentage points in the jiaogulan group versus 0.2 percentage points in controls (p<0.001). These are clinically meaningful improvements — a 2-point HbA1c reduction is comparable to what many pharmaceutical interventions achieve.

A follow-up crossover trial (PMID 23431428) used a more rigorous method — the somatostatin-insulin-glucose infusion test (SIGIT) — to directly measure insulin sensitivity rather than relying on indirect markers [2]. After four weeks of jiaogulan tea versus placebo, the jiaogulan group had significantly lower fasting plasma glucose and a significantly lower steady-state plasma glucose during the SIGIT (p<0.001), confirming that improved insulin sensitivity, not just reduced glucose production, underlies the effect.

Cholesterol and Triglycerides

The 2022 systematic review and meta-analysis (PMID 36091752) is the most comprehensive evidence assessment to date [3]. Researchers identified 22 randomized controlled trials involving 2,407 participants with dyslipidemia. Results showed that jiaogulan (used alone or as adjunctive therapy) produced statistically significant reductions in total cholesterol, LDL cholesterol, and triglycerides, with modest improvements in HDL. The authors note that the effect size was comparable to that of omega-3 fatty acids and red yeast rice.

The proposed mechanisms include: SREBP-2-HMGCR pathway inhibition (the same target as statin drugs, though via different mechanisms), increased LDL receptor expression, upregulation of bile acid biosynthetic pathways that excrete cholesterol, and PPAR-pathway effects on fat metabolism.

Exercise Performance and Mitochondrial Function

A 2023 randomized double-blind crossover trial (PMID 38004115) tested 450 mg/day of jiaogulan extract (equivalent to 2.25 g dried leaf) versus placebo in 16 healthy untrained young men for four weeks, separated by a four-week washout [4]. Key findings:

Participants improved 20 km cycling time trial performance
Muscle AMPK Thr172 phosphorylation (the active, phosphorylated form of AMPK) was significantly higher after exercise in the jiaogulan group
Mitochondrial oxygen flux was higher in the jiaogulan group
Fasting blood glucose and leptin were significantly lower

This suggests jiaogulan's benefits extend beyond populations with metabolic dysfunction. Activating AMPK in muscle during exercise may enhance training adaptations by upregulating mitochondrial biogenesis and fat oxidation — similar to how some endurance athletes use other AMPK activators.

Using Jiaogulan

As a tea: The traditional preparation is simply dried leaves steeped in hot (not boiling) water for 3–5 minutes. The flavor is lightly sweet and grassy. Many people drink 1–3 cups daily. Jiaogulan tea is widely available online and in health food stores. Look for whole dried leaves rather than tea bags, which may contain lower-quality material.

As a supplement: Standardized extracts typically deliver 450–500 mg per day in clinical trials. Look for products standardized to gypenosides (often 20–80% standardization). Some products use a proprietary "ActivAMP" extract specifically standardized for AMPK activation.

Timing: For blood sugar management, consuming jiaogulan tea before or with meals may be most effective, as it can blunt postprandial glucose spikes. For exercise benefits, the trials used daily supplementation rather than acute dosing.

Safety: Jiaogulan appears well-tolerated in clinical trials. The most commonly reported side effect is loose stools at higher doses. Because it lowers blood sugar, people on diabetes medications should use it cautiously and monitor glucose levels to avoid hypoglycemia.

Related reading: See our Berberine page for another plant compound that activates AMPK with substantial clinical evidence. Our Ginseng page covers the closely related ginsenosides. For insulin resistance more broadly, see our Insulin Resistance page.

Evidence Review

Huyen et al. (2010) — Randomized Controlled Trial, Hormone and Metabolic Research [1]

This was a double-blind, placebo-controlled trial in 24 drug-naive Vietnamese patients with type 2 diabetes, randomized to 6 g/day of authenticated jiaogulan tea or placebo tea for 12 weeks. Authentication of the plant material was conducted to confirm species identity, addressing a common quality-control concern with botanical trials.

The primary outcomes were fasting plasma glucose (FPG) and HbA1c. At 12 weeks, FPG decreased by 3.0 ± 1.8 mmol/L in the jiaogulan group compared to 0.6 ± 2.2 mmol/L in controls (p<0.01). HbA1c dropped by approximately 2 percentage points versus 0.2 points in controls (p<0.001). No serious adverse events were reported.

Limitations: small sample (n=24), single-center, short duration for HbA1c assessment, and conducted in a drug-naive population (results may differ in patients already on diabetes medications).

Huyen et al. (2013) — Randomized Crossover Trial, Journal of Nutrition and Metabolism [2]

This follow-up used a rigorous crossover design with a somatostatin-insulin-glucose infusion test (SIGIT), which directly quantifies insulin sensitivity by clamping insulin and glucose levels and measuring steady-state plasma glucose (SSPG). Lower SSPG = better insulin sensitivity.

Patients received jiaogulan or placebo tea for four weeks, crossed over with a two-week washout. Both FPG and SIGIT-measured SSPG were significantly lower after jiaogulan treatment (p<0.001). The crossover design controls for inter-individual variation, strengthening the causal inference. This trial provides direct evidence of improved insulin sensitivity — not merely reduced glucose through other mechanisms.

Limitations: short intervention period (4 weeks), small sample, same research group as the 2010 trial (independent replication would strengthen confidence).

Dai et al. (2022) — Systematic Review and Meta-Analysis, Frontiers in Pharmacology [3]

This is the most comprehensive evidence synthesis available on jiaogulan. The review systematically searched multiple databases and identified 22 RCTs involving 2,407 participants with dyslipidemia. Gynostemma pentaphyllum was used alone in some trials and as adjunctive therapy (alongside statins or fibrates) in others.

Pooled results showed statistically significant reductions in: total cholesterol, LDL cholesterol, and triglycerides. HDL cholesterol improved modestly. The effects were deemed comparable to omega-3 fatty acids and red yeast rice on normalization of serum lipids — both of which are widely recommended interventions.

The authors rated the overall evidence quality as moderate. Key limitations noted: heterogeneity in jiaogulan preparations, doses, and durations across trials; many trials conducted in China with limited information on allocation concealment; and relatively short follow-up periods (most trials were 1–3 months).

Nayyar et al. (2023) — Randomized Crossover Trial, Nutrients [4]

This is the only published human RCT examining jiaogulan's effects in healthy, non-diabetic individuals with a focus on exercise performance and mechanistic endpoints. Sixteen healthy untrained young males completed a double-blind crossover study: 4 weeks of 450 mg/day jiaogulan extract versus placebo, with 4-week washout.

After jiaogulan supplementation, participants improved their 20 km cycling time trial performance. Post-exercise muscle biopsies showed significantly higher AMPK Thr172 phosphorylation (the activated form), confirming that the compound reaches skeletal muscle and activates the target pathway at physiologically relevant doses. Mitochondrial oxygen flux was also higher in the jiaogulan condition. Fasting leptin and blood glucose were significantly lower.

This trial provides direct mechanistic evidence in humans that jiaogulan activates AMPK in skeletal muscle during exercise, extending the animal and cell data to the human system. Limitations: small sample (n=16), young healthy males only, single laboratory, one dose tested.

Su et al. (2021) — Comprehensive Review, Molecules [5]

This review summarized more than 230 isolated compounds from jiaogulan, with the majority being gypenosides. The authors catalogued pharmacological activities including: anti-diabetic, lipid-lowering, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anxiolytic effects. Most of these data come from animal models and cell studies.

The review confirms the broad bioactivity of jiaogulan's phytochemical profile and provides mechanistic detail on pathways beyond AMPK, including SIRT1 upregulation (a longevity-associated deacetylase), Nrf2 antioxidant pathway activation, and suppression of NF-κB inflammatory signaling.

Evidence Summary

Human clinical evidence for jiaogulan is moderate in quality but internally consistent. The most robust signal is for blood sugar reduction in type 2 diabetes, supported by two RCTs with direct mechanistic confirmation (SIGIT). The dyslipidemia evidence rests on a large meta-analysis of 22 trials, though most were short-term. Exercise performance improvement has been demonstrated in one crossover trial with mechanistic validation via muscle biopsy.

The overall picture: jiaogulan activates AMPK in human muscle, reduces blood glucose and HbA1c in type 2 diabetic patients, and improves lipid profiles in dyslipidemic populations. Its traditional reputation for supporting energy and longevity maps reasonably well onto these modern findings. Evidence strength is preliminary-to-moderate; larger, longer trials would substantially increase confidence.

References

Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patientsHuyen VTT, Phan DV, Thang P, Hoa NK, Östenson CG. Hormone and Metabolic Research, 2010. PubMed 20213586 →
Gynostemma pentaphyllum Tea Improves Insulin Sensitivity in Type 2 Diabetic PatientsHuyen VT, Phan DV, Thang P, Hoa NK, Östenson CG. Journal of Nutrition and Metabolism, 2013. PubMed 23431428 →
Gynostemma pentaphyllum for dyslipidemia: A systematic review of randomized controlled trialsDai N, Zhao FF, Fang M, Pu FL, Kong LY, Liu JP. Frontiers in Pharmacology, 2022. PubMed 36091752 →
Gynostemma Pentaphyllum Increases Exercise Performance and Alters Mitochondrial Respiration and AMPK in Healthy MalesNayyar D, Yan X, Xu G, Shi M, Garnham AP, Mathai ML, McAinch AJ. Nutrients, 2023. PubMed 38004115 →
Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllumSu C, Li N, Ren R, Wang Y, Su X, Lu F, Zong R, Yang L, Ma X. Molecules, 2021. PubMed 34684830 →