Double-Blind, Placebo-Controlled, Parallel-Group Randomized Controlled Trial to Evaluate the Efficacy and Safety of Nimsai Herbal in Patients With Grade 2-3 Hemorrhoids

The current understanding of hemorrhoid pathogenesis has remained largely unchanged for over two centuries, positing hemorrhoids primarily as isolated venous dilatations or prolapses. This traditional view, however, fails to adequately explain the high recurrence rates post-treatment, the limited efficacy of topical agents, and the often-debilitating symptomatology. Our extensive research, culminating in the "War-Drill Model" and the "Sine Qua Non Hypothesis," fundamentally challenges this conventional paradigm. We propose that hemorrhoids are not primarily structural abnormalities but rather a manifestation of underlying venous congestion, which then secondarily leads to vascular deformation and associated symptoms. This congestion acts as the indispensable (sine qua non) prerequisite for the development of both symptomatic and asymptomatic hemorrhoidal disease.

The "War-Drill Model" further categorizes this venous congestion based on its etiology:

War Mode Hemorrhoids: These are hypothesized to arise from chronic or passive venous congestion triggered by an underlying systemic or local inflammatory process or pathology. Examples include inflammatory bowel diseases (Crohn's disease, ulcerative colitis), anal fissures, rectal polyps, liver diseases causing portal hypertension, and various other systemic conditions affecting vascular flow or integrity. Crucially, "War Mode" hemorrhoids may serve as a critical "biological early-warning system," prompting investigations that could lead to the early diagnosis of up to 20 distinct and potentially severe internal diseases.

Drill Mode Hemorrhoids: These are hypothesized to be transient vascular engorgements resulting from physiological hormonal fluctuations, typically observed during periods of significant endocrine change such as adolescence, pregnancy, lactation, menopause, and andropause. These episodes are often self-limiting, resolving as hormonal balance stabilizes.

To validate a systemic therapeutic approach based on this new model, we conducted a double-blind, placebo-controlled, parallel-group Randomized Controlled Trial (RCT) (Protocol ID: NA-2024-01). The study enrolled 300 participants aged 18-70 years with endoscopically confirmed Grade 2-3 internal hemorrhoids and a history of symptoms for over 6 weeks. Participants were randomized to receive either Nimsai Herbal (a novel systemic botanical formulation, 600 mg daily) or an identical placebo for 10 consecutive days.