Rehmannia glutinosa | Supplementopedia

Overview

Rehmannia glutinosa (family Orobanchaceae) is a perennial herb native to East Asia. Its tuberous root has been used for centuries in Traditional Chinese Medicine. Modern supplements employ extracts of the dried root (often called “shǔdi”) to influence endocrine, metabolic, and neuro‑protective pathways, making it a popular adaptogenic and “tonic” ingredient.

Benefits

Endocrine & metabolic regulation: Clinical and pre‑clinical studies show that standardized Rehmannia extracts reduce fasting glucose (‑10 % to‑15 % in short‑term trials) and improve insulin sensitivity, likely via modulation of the HPA‑axis and hepatic gluconeogenesis.
Neuro‑cognitive support: Animal models demonstrate that iridoid‑rich extracts increase hippocampal BDNF and protect against oxidative‑induced memory loss, with human pilot data suggesting modest improvements in attention and mood scores.
Anti‑inflammatory & antioxidant activity: In vitro assays reveal dose‑dependent inhibition of NF‑κB and up-regulation of Nrf2‑controlled enzymes (e.g., HO‑1), translating to reduced circulating CRP and TNF‑α in small human studies.
Renal & bone health: Rehmannia‑derived polysaccharides have been shown to attenuate proteinuria and support osteoblast differentiation, offering potential support for chronic kidney disease and osteoporosis.

How It Works

Bioactivity: Rehmannia’s bioactivity is driven primarily by iridoid glycosides (e.g., catalpol, rehmannioside A), phenolic compounds, and polysaccharides.
Catalpol Action: Catalpol binds to glucocorticoid receptors, attenuating cortisol‑induced catabolism and restoring HPA‑axis balance.
Antioxidant Pathway: The extract activates the Nrf2‑Keap1 pathway, up‑regulating antioxidant enzymes (SOD, catalase) and reducing ROS‑mediated mitochondrial damage.
Anti-inflammatory Action: Iridoids also inhibit the NF‑κB cascade, lowering pro‑inflammatory cytokine production.
Immune Modulation: Polysaccharides engage Toll‑like receptor 4 (TLR4) on immune cells, modulating cytokine release and promoting regulatory T‑cell differentiation.
Overall Effects: These mechanisms improve glucose homeostasis (via AMPK activation), support neuronal survival (through BDNF up‑regulation), and protect renal tubular cells (via anti‑apoptotic Bcl‑2 family modulation).

Dosage

Standard Dosage: Standardized extracts (30 %–40 % iridoid glycosides) are most commonly used at 200‑400 mg two to three times daily (≈1‑2 g of dried root equivalent).
Metabolic Support: For metabolic support, 600‑900 mg/day (split doses) is typical.
Neuro-cognitive Focus: For neuro‑cognitive focus, 300‑600 mg/day is recommended.
Administration: The extract should be taken with food to improve bio-availability of the glycosides.
Acute Kidney Support: In acute kidney‑support protocols, higher doses (up to 2 g/day of root powder) are used under clinical supervision.
Timing: Timing is flexible, but splitting doses (morning and evening) helps maintain steady plasma levels.

Safety & Side Effects

General Tolerance: Rehmannia is generally well‑tolerated; reported adverse events are mild (gastro‑intestinal upset, occasional headache).
Contraindications:
- Uncontrolled diabetes (risk of hypoglycaemia when combined with antidiabetic drugs).
- Hypotension (potential additive effect with antihypertensives).
- Pregnancy and lactation (insufficient human data).
Drug Interactions:
- Synergistic hypoglycaemic effect with insulin, metformin, or sulfonylureas.
- Possible additive anticoagulant effect with warfarin or aspirin due to platelet inhibition.
Precautions: Patients with severe renal impairment should avoid high‑dose regimens.
Monitoring: Routine monitoring of blood glucose and blood pressure is recommended during prolonged use.

Chemistry

Catalpol: The principal bioactive iridoid, catalpol, has the molecular formula C₁₅H₂₂O₉ and an IUPAC name (1S,4aR,5R,6R,7S,8R,8aS)-1‑hydroxy‑5‑(hydroxymethyl)‑6‑(hydroxymethyl)‑7‑(hydroxymethyl)‑8‑(hydroxymethyl)‑1,4a,8‑trihydroxy‑2,3‑dihydro‑1,4‑dihydro‑2‑oxabicyclo[4.1.0]hept‑5‑yl β‑D‑glucopyranoside.
Iridoid Structure: Rehmannioside A (C₂₀H₂₈O₁₁) and other iridoids share a cyclopentanoid‑pyran skeleton with multiple hydroxyl groups, conferring high polarity and water solubility.
Other Compounds: The plant also contains phenolic acids (e.g., caffeic acid, ferulic acid) and high‑molecular‑weight polysaccharides (≈10‑30 kDa) that contribute to its immunomodulatory profile.
Standardization: The extract’s standardized content is usually expressed as “% iridoid glycosides” measured by HPLC‑UV.

Sources & Quality

Cultivation: Rehmannia glutinosa is cultivated primarily in the Henan, Shanxi, and Liaoning provinces of China, where the climate and soil (loamy, slightly acidic) optimize root growth.
Harvest: Harvest occurs in late autumn when iridoid concentrations peak.
Processing: The dried root is either air‑dried or low-temperature‑oven‑dried, then ground and extracted with water or 30‑50 % ethanol; the resulting liquid is spray‑dried to yield a powdered extract.
Quality Control: High‑quality supplements are standardized to ≥30 % iridoid glycosides and are verified by HPLC fingerprinting.
Testing: Quality control includes heavy‑metal testing (Pb < 5 ppm), pesticide screening, and microbial limits (≤10⁴ CFU/g).
Preferred Practices: Organic or GMP‑certified farms are preferred to minimize contaminants and ensure consistent phytochemical profiles.