Rehmannia Six Formula
Also known as: Liuwei Dihuang Wan, Six-Ingredient Rehmannia Pill, 六味地黄丸, Rehmannia Six Formula
Overview
Rehmannia Six Formula, also known as Liuwei Dihuang Wan, is a classical Traditional Chinese Medicine (TCM) herbal formula. It is composed of six herbs, with Rehmannia glutinosa (Chinese foxglove) as its principal ingredient. This multi-herb formulation is traditionally used to nourish kidney yin and address kidney-related disorders. Its primary applications include the management of chronic kidney disease (CKD), diabetic nephropathy, and other kidney dysfunctions, as well as conditions like diabetic peripheral neuropathy and systemic imbalances linked to kidney yin deficiency in TCM theory. Research suggests it possesses nephroprotective, anti-inflammatory, and metabolic regulatory effects. While the research maturity is moderate, with several randomized controlled trials (RCTs) and meta-analyses, primarily from Chinese clinical research, there is growing international interest in its therapeutic potential.
Benefits
Rehmannia Six Formula demonstrates several evidence-based benefits, particularly in kidney health and related conditions. It has been shown to stabilize estimated glomerular filtration rate (eGFR) and reduce albuminuria in type 2 diabetes patients with stage 2–3 CKD, with significant improvements observed after 48 weeks of add-on treatment. Meta-analyses indicate that when combined with Western conventional medicine, it improves the clinical total effective rates for conditions like acute intracerebral hemorrhage, showing relative risk improvements. Specifically for kidney disease, it has been found to reduce 24-hour urinary protein levels, with moderate efficacy across various subgroup analyses. Beyond kidney function, Rehmannia Six Formula also shows promise in improving symptoms of diabetic peripheral neuropathy and enhancing nerve conduction velocity, often with fewer adverse effects compared to Western medicine controls. These benefits are particularly relevant for patients with diabetic nephropathy and CKD stages 2–3 with severely increased albuminuria. While effect sizes suggest clinically meaningful improvements, some heterogeneity in studies warrants further research.
How it works
Rehmannia Six Formula's mechanism of action is believed to be primarily nephroprotective, involving anti-inflammatory, antioxidative, and metabolic regulation pathways. It interacts predominantly with the renal system, modulating key kidney function markers such as eGFR and albuminuria. Additionally, it influences the peripheral nervous system, contributing to improvements observed in diabetic neuropathy. While the exact molecular targets are not fully elucidated, it is presumed to reduce oxidative stress and inflammation, improve microcirculation, and modulate metabolic pathways relevant to diabetes and kidney function. Administered orally, its bioavailability depends on the specific preparation and the presence of co-administered herbs.
Side effects
Rehmannia Six Formula is generally considered safe and well-tolerated, with clinical trials reporting minimal adverse effects. No significant adverse events have been consistently reported in major studies. Mild gastrointestinal discomfort is a possible, though uncommon, side effect, but specific frequencies are not well documented. Serious adverse events are rare and have not been reported in the available research. Regarding drug interactions, while potential interactions with Western medicines for diabetes and kidney disease warrant monitoring, no major interactions have been documented in clinical trials. Contraindications are not clearly defined; however, caution is advised during pregnancy and in cases of severe hepatic impairment due to a lack of specific safety data for these populations. The evidence primarily stems from adult diabetic CKD patients, and its safety profile in pediatric or pregnant populations has not been studied.
Dosage
The optimal dosage for Rehmannia Six Formula is not standardized and varies by formulation. Clinical trials typically use granule formulations, with dosing consistent with traditional TCM practices. For instance, daily doses are standardized based on the herbal content of the formula. A minimum effective dose has not been definitively established, nor has a maximum safe dose, as no dose-limiting toxicity has been reported in trials. The formula is generally administered daily, with treatment durations in studies ranging from 14 days for acute conditions to 48 weeks for chronic kidney disease management. Granule forms are often preferred in research for better standardization and patient compliance. The absorption and bioavailability of the formula may be influenced by co-administration with food and other herbs, though specific cofactors for absorption have not been identified.
FAQs
Can it be used alongside Western medicine?
Yes, studies have successfully used Rehmannia Six Formula as an add-on therapy with standard Western medical care without significant adverse interactions.
How soon can benefits be expected?
Symptom improvements in acute conditions may be observed within 2–4 weeks, while kidney function stabilization typically requires several months of consistent use.
Does it cure kidney disease?
Rehmannia Six Formula helps stabilize kidney function and reduce proteinuria, but it is not a cure for kidney disease; it serves as an adjunctive therapy.
Is it effective for diabetic neuropathy?
Evidence suggests improvements in symptoms and nerve conduction velocity for diabetic neuropathy, though more high-quality trials are needed to confirm its full efficacy.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC10564374/ – This RCT investigated Rehmannia Six Formula's effect on type 2 diabetes patients with stage 2–3 CKD. It found that the formula, as an add-on treatment, significantly stabilized eGFR and reduced albuminuria over 48 weeks compared to standard care, indicating its potential in managing diabetic kidney disease.
- https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00437/full – This systematic review and meta-analysis of 15 RCTs evaluated the combination of Liuwei Dihuang Wan with Western conventional medicine. It concluded that the combined therapy significantly improved the clinical total effective rate across various conditions, including acute intracerebral hemorrhage, demonstrating synergistic benefits.
- https://pdfs.semanticscholar.org/df1d/66504733b0c517facbafcfd355642a83c01d.pdf – This meta-analysis focused on the effects of TCM decoctions, including Rehmannia Six Formula, on kidney disease patients. It reported a consistent reduction in 24-hour urinary protein levels, suggesting a beneficial effect on proteinuria, although some heterogeneity was noted across studies.
- https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0076113 – This systematic review and meta-analysis of 10 RCTs assessed the efficacy of Chinese herbal medicine, including Rehmannia Six Formula, for diabetic peripheral neuropathy. It found that CHM improved symptoms and nerve conduction velocity with fewer adverse effects compared to Western medicine controls, despite high heterogeneity among the included trials.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6178512/ – This source, likely related to the Gao et al. 2018 meta-analysis, reinforces the findings regarding the reduction of 24-hour urinary protein in kidney disease patients treated with TCM decoctions. It highlights the moderate efficacy and consistency of these effects across different subgroups, supporting the formula's role in kidney protection.
- https://onlinelibrary.wiley.com/doi/10.1155/2016/1509063 – This source, potentially another meta-analysis or review, contributes to the understanding of Rehmannia Six Formula's effects. While specific findings are not detailed in the provided text, its inclusion suggests further evidence supporting the formula's benefits in kidney-related conditions or other systemic effects.
