Digexin® - Clinical Research Data Summary
Digexin® Ashwagandha & Okra Botanical Blend
Digexin® is a clinically studied ingredient used in the following Silver Fern™ Brand product:
Introduction
Digexin® is a proprietary botanical ingredient composed of standardized extracts of Withania somnifera (Ashwagandha) root and Abelmoschus esculentus (Okra) fruit. These botanicals have long histories of use in traditional wellness practices for supporting digestive function, stress balance, and gastrointestinal comfort. Digexin® is designed to support digestive health through mechanisms associated with the gut–brain axis, including signaling pathways that influence gastrointestinal motility, digestive comfort, and stress-related digestive responses.
Multiple clinical investigations have evaluated the Digexin® botanical blend (CL18100F4) in adults experiencing functional constipation or digestive discomfort. Randomized, double-blind, placebo-controlled trials in 48 and 135 adults demonstrated improvements in validated constipation symptom scores, bowel movement frequency, gastrointestinal transit time, and digestive comfort. Benefits were observed as early as 7–14 days and continued throughout supplementation periods of up to 60 days. These studies also reported favorable changes in biomarkers associated with gut signaling, inflammation balance, and intestinal barrier function. Additional exploratory research has evaluated the ingredient in individuals experiencing gastrointestinal symptoms during oral semaglutide therapy. A narrative review published in Cureus also summarizes the clinical evidence and highlights the potential role of this botanical combination in supporting digestive function through gut–brain axis modulation.*
These are the studies for Digexin®. Below, we provided a summary of each key data for each study, along with a link to the complete clinical research.
- Summary of Study 1 – Full Study: https://pubmed.ncbi.nlm.nih.gov/37543151/
- Summary of Study 2 – Full Study: https://pubmed.ncbi.nlm.nih.gov/38691810/
- Summary of Study 3 – Full Study: Clinical Trials Registry of India – CTRI/2024/12/078105
- Summary of Study 4 – Full Study: https://pubmed.ncbi.nlm.nih.gov/39139804/
Ingredient Manufacturer Link: https://nxt-usa.com/what_is_digexin/
Study 1 Summary
Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/37543151/
A Blend of Withania somnifera (L.) Dunal Root and Abelmoschus esculentus (L.) Moench Fruit Extracts Relieves Constipation and Improves Bowel Function: A Proof-of-Concept Clinical Investigation
J Ethnopharmacol. 2024 Jan 10;318(Pt B):116997. doi: 10.1016/j.jep.2023.116997. Epub 2023 Aug 4. PMID: 37543151.
A randomized, double-blind, placebo-controlled clinical study evaluated the effects of a proprietary blend of Withania somnifera (Ashwagandha) root extract and Abelmoschus esculentus (Okra) fruit extract (CL18100F4, Digexin®) on bowel function and quality of life in adults with functional constipation. Forty-eight participants meeting Rome III criteria for constipation were randomized to receive 300 mg, 500 mg, or placebo daily for 14 days. Compared with placebo, Digexin® supplementation significantly improved validated constipation symptom scores, gastrointestinal comfort, and quality-of-life measures. Participants also showed improvements in stress markers, sleep quality, and gut-brain signaling biomarkers.
Study Design Highlights
- Study design: Randomized, double-blind, placebo-controlled clinical trial
- Participants: 48 adults (ages 25–60) with functional constipation meeting Rome III criteria
- Duration: 14 days
- Groups:
- Placebo
- 300 mg Digexin® daily
- 500 mg Digexin® daily
- Primary assessments: PAC-SYM, PAC-QOL, GSRS, stress and sleep assessments, biomarkers
Key Findings (What the Study Showed)
1. Constipation Symptom Improvement
Digexin® significantly improved validated constipation and gastrointestinal symptom scores compared with placebo:
- PAC-SYM score: significantly improved (p < 0.0001)
- PAC-QOL score: significantly improved (p < 0.0001)
- GSRS score: significantly improved (p < 0.0001)
- Improvements in bowel movement regularity, stool comfort, abdominal discomfort, and bloating
- All improvements occurred within 14 days
2. Gut-Brain Biomarker Changes
Participants receiving 500 mg/day experienced measurable physiological changes:
- Increased: Serotonin, Gastrin, Interleukin-10 (anti-inflammatory cytokine)
- Decreased: Cortisol (stress hormone), Interleukin-6 (pro-inflammatory cytokine)
3. Improvements in Stress and Sleep
- Significant improvements in sleep quality scores
- Significant improvements in stress scores
4. Safety and Tolerability
- No adverse events reported
- Blood chemistry, hematology, vital signs, and urinalysis remained within normal ranges
Benefits of Digexin® Demonstrated by This Study
Based directly on the clinical outcomes, Digexin® was shown to:
✓ Support improvements in validated constipation symptom scores within 14 days
✓ Support bowel movement regularity and stool comfort
✓ Help reduce bloating and abdominal discomfort
✓ Support healthy serotonin and gastrin signaling in the gut
✓ Support reduced cortisol and inflammatory markers
✓ Support sleep quality and stress balance
✓ Be well tolerated with no adverse events at either dose
Why This Study Matters
This study suggests Digexin® may support several everyday digestive and wellness concerns by targeting the gut–brain axis simultaneously. The rapid improvements within just 14 days — alongside favorable biomarker changes in serotonin, gastrin, cortisol, and inflammatory markers — support the proposed mechanism by which Ashwagandha and Okra work together to address both the neurological and physiological aspects of digestive comfort.*
Reference Link: https://pubmed.ncbi.nlm.nih.gov/37543151/
Study 2 Summary
Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/38691810/
A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study
J Am Nutr Assoc. 2024 Aug;43(6):553-566. doi: 10.1080/27697061.2024.2346073. Epub 2024 May 1. PMID: 38691810.
A randomized, double-blind, placebo-controlled clinical trial evaluated the effects of CL18100F4 on bowel function and quality of life in 135 adults with functional constipation meeting Rome IV criteria. Participants received placebo, 300 mg, or 500 mg of CL18100F4 daily for 60 days. Participants taking CL18100F4 experienced significant improvements in validated constipation symptom scores, gastrointestinal comfort, bowel movement frequency, and gastrointestinal transit time compared with placebo. Improvements were observed as early as day 7 and were accompanied by favorable changes in gut-brain and gut-barrier biomarkers.
Study Design Highlights
- Study design: Randomized, double-blind, placebo-controlled clinical trial
- Participants: 135 adults (ages 25–60) with functional constipation meeting Rome IV criteria
- Duration: 60 days
- Groups:
- Placebo
- 300 mg CL18100F4 daily
- 500 mg CL18100F4 daily
- Primary assessments: PAC-SYM, PAC-QOL, GSRS, Gastrointestinal Transit Time (GIT), Complete Spontaneous Bowel Movements (CSBM), sleep quality and mood assessments, gut-related biomarkers
Key Findings (What the Study Showed)
1. Constipation Symptoms (PAC-SYM)
Participants taking CL18100F4 experienced substantial reductions in constipation symptom scores compared with placebo, with improvements of approximately 35–45% depending on dose and timepoint.
2. Quality of Life (PAC-QOL)
Participants reported improvements in constipation-related quality of life of approximately 30–40%.
3. Gastrointestinal Symptoms (GSRS)
Digestive symptom scores related to bloating, discomfort, and digestive distress improved by roughly 30–40% compared with baseline.
4. Bowel Movements and Transit Time
- Complete spontaneous bowel movements increased, indicating improved bowel regularity and motility
- Gastrointestinal transit time improved significantly compared with placebo
- Improvements first observed beginning as early as day 7 and continuing through day 60
5. Gut-Brain and Gut-Barrier Biomarker Changes
- Increased: Serotonin, Gastrin, Interleukin-10, Diamine oxidase (DAO)
- Decreased: Interleukin-6, Cortisol, Zonulin
6. Safety and Tolerability
- No major adverse events observed
- Vital signs, blood chemistry, hematology, and urinalysis remained within normal ranges
Benefits of Digexin® Demonstrated by This Study
Based directly on the clinical outcomes, Digexin® (CL18100F4) was shown to:
✓ Support 35–45% improvements in constipation symptom scores
✓ Support 30–40% improvements in constipation-related quality of life
✓ Support more regular and spontaneous bowel movements
✓ Support significant improvements in gastrointestinal transit time
✓ Support favorable changes in serotonin, gastrin, and gut-barrier markers
✓ Support reductions in zonulin (intestinal permeability marker)
✓ Produce benefits as early as day 7, continuing through day 60
✓ Be well tolerated with no major adverse events
Why This Study Matters
This larger, longer-duration trial confirms and extends the findings from Study 1 across 135 participants over 60 days. The combination of improved bowel frequency, transit time, digestive symptoms, and gut-barrier biomarkers supports Digexin®'s proposed mechanism of action through gut–brain axis modulation. The early onset of benefits at day 7 and continued improvement through 60 days makes this evidence particularly relevant for individuals seeking reliable, sustained digestive support.*
Reference Link: https://pubmed.ncbi.nlm.nih.gov/38691810/
Study 3 Summary
Complete Study Information: Clinical Trials Registry of India – CTRI/2024/12/078105. https://ctri.nic.in/Clinicaltrials/login.php
An Open-Label, Single-Arm Study to Evaluate the Efficacy of CL18100F4 to Improve Gastrointestinal Symptoms in Subjects Using Oral Semaglutide Therapy
Study report summary. 2025. Confidential clinical investigation report.
An open-label, single-arm clinical investigation evaluated the effects of CL18100F4 in 12 adults experiencing gastrointestinal symptoms while using oral semaglutide therapy. Participants were supplemented with 500 mg of CL18100F4 daily for 21 days. The study assessed changes in gastrointestinal symptoms commonly associated with GLP-1 receptor agonist use, including digestive discomfort and bowel irregularity.
Study Design Highlights
- Study type: Open-label, single-arm proof-of-concept clinical study
- Participants: 12 adults using oral semaglutide therapy
- Dose: 500 mg CL18100F4 daily
- Duration: 21 days
- Objectives: Evaluate the effect of CL18100F4 on gastrointestinal symptoms during oral semaglutide therapy; assess tolerability and safety
Key Findings (What the Study Showed)
Participants taking CL18100F4 during semaglutide therapy reported improvements in several digestive symptoms commonly associated with GLP-1 medications:
- Improvements in gastrointestinal comfort
- Improvements in bowel regularity
- Reductions in digestive discomfort
- No significant safety concerns reported
- Supplement was well tolerated during the study period
Benefits of Digexin® Demonstrated by This Study
Based directly on the study findings, CL18100F4 was shown to:
✓ Support digestive comfort during altered gut motility states
✓ Support bowel regularity in individuals using GLP-1 medications
✓ Be well tolerated alongside oral semaglutide therapy
✓ Provide preliminary evidence for gut motility and gut-brain signaling support
Why This Study Matters
GLP-1 medications such as semaglutide are known to influence gastrointestinal motility and can sometimes lead to digestive symptoms including slowed digestion, nausea, or constipation. This preliminary investigation provides early evidence that the Digexin® botanical blend may help support digestive comfort and bowel function in individuals experiencing altered gastrointestinal motility. Because the study was small and open-label, the findings should be considered preliminary but supportive of Digexin®'s proposed mechanisms related to digestive motility and gut–brain function.*
Reference Link: Clinical Trials Registry of India – CTRI/2024/12/078105. https://ctri.nic.in/Clinicaltrials/login.php
Study 4 Summary
Complete Study Information: https://pubmed.ncbi.nlm.nih.gov/39139804/
Addressing GI Health Through the Bidirectional Modulation of the Gut-Brain Axis With Herbal Extracts: A Narrative Review
Cureus. 2024.
A narrative review published in Cureus evaluated the role of herbal ingredients in supporting gastrointestinal health through modulation of the gut–brain axis. The review highlights research on CL18100F4, the proprietary blend of Withania somnifera (Ashwagandha) root extract and Abelmoschus esculentus (Okra) fruit extract used in Digexin®. The authors summarize findings from the 14-day proof-of-concept trial in 48 participants and the larger 60-day randomized controlled trial in 135 participants, and discuss the proposed mechanisms by which the Ashwagandha and Okra combination may support gut–brain signaling and digestive motility.
Key Findings Summarized in This Review
1. Digestive Outcomes
- Reduced constipation symptom scores
- Improved bowel movement frequency
- Improved gastrointestinal transit time
- Improved digestive comfort and reduced gastrointestinal symptoms
2. Quality of Life Outcomes
- Improved constipation-related quality-of-life scores
- Improvements in sleep quality
- Improvements in mood-related measures
3. Gut-Brain Biomarkers
- Increased: Serotonin, Gastrin, Interleukin-10
- Decreased: Cortisol, Interleukin-6
- Improved: Zonulin and diamine oxidase (intestinal barrier markers)
4. Proposed Mechanism
The authors explain that the gastrointestinal system and nervous system communicate through multiple mechanisms, including neurotransmitters such as serotonin, stress hormones such as cortisol, inflammatory signaling pathways, and gut motility regulation. The Ashwagandha and Okra botanical combination is proposed to support these communication pathways bidirectionally.
Benefits of Digexin® Summarized by This Review
Based directly on the reviewed clinical evidence, Digexin® (CL18100F4) was shown to:
✓ Support healthy gastrointestinal motility
✓ Support balanced gut–brain communication
✓ Support digestive comfort and bowel regularity
✓ Support stress-related digestive responses
✓ Support improvements in sleep quality and mood-related measures connected to gut–brain signaling
Why This Study Matters
This narrative review provides scientific context for understanding how the Digexin® botanical blend supports digestive health through gut–brain axis modulation rather than simply acting as a bulking agent or motility stimulant. The bidirectional nature of gut–brain signaling — involving serotonin, cortisol, inflammatory pathways, and motility regulation — helps explain why the Ashwagandha and Okra combination addresses multiple aspects of digestive wellness simultaneously.*
Reference Link: https://pubmed.ncbi.nlm.nih.gov/39139804/
Big-Picture Integration with Other Studies
- Study 1: In a 14-day randomized, double-blind, placebo-controlled trial (n=48), 300–500 mg/day of Digexin® significantly improved constipation symptoms, bowel function, gastrointestinal comfort, stress markers, and sleep quality compared with placebo, with excellent tolerability.
- Study 2: In a 60-day randomized, double-blind, placebo-controlled clinical study involving 135 adults with functional constipation, daily supplementation with 300 mg or 500 mg of CL18100F4 significantly improved bowel movement frequency, gastrointestinal transit time, digestive comfort, sleep quality, and quality-of-life scores compared with placebo, with benefits observed as early as 7 days.
- Study 3: In a 21-day open-label proof-of-concept study in adults using oral semaglutide, daily supplementation with 500 mg of CL18100F4 was associated with improvements in gastrointestinal comfort and digestive symptoms and was well tolerated.
- Study 4: A 2024 narrative review summarized clinical research on CL18100F4, highlighting randomized controlled trials demonstrating improvements in constipation symptoms, gastrointestinal function, and gut–brain signaling markers.
Digexin® Ingredient Summary & Real-World Relevance
Collectively, the available research suggests that Digexin® may help support digestive comfort, bowel regularity, and healthy gastrointestinal function. Clinical studies indicate that the botanical blend may support normal digestive motility, improvements in constipation-related quality-of-life measures, and balanced gut–brain signaling pathways associated with stress and digestive health. The ingredient has also demonstrated good tolerability in clinical trials.
In practical terms, these findings suggest Digexin® may be a helpful nutritional ingredient for individuals seeking support for digestive regularity, occasional constipation, and digestive comfort during periods of stress or altered gastrointestinal function. By supporting the communication pathways between the digestive system and the nervous system, Digexin® may help promote a more balanced digestive experience and overall digestive wellness as part of a healthy lifestyle.*
Ingredient Manufacturer Link: https://nxt-usa.com/what_is_digexin/
Digexin® is a clinically studied ingredient used in the following Silver Fern™ Brand product:
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.