Functional gastrointestinal disorders (FGID) impact 40 percent of the global population.1 FGID are a group of disorders with no identified etiology characterized by chronic gastrointestinal (GI) symptoms including abdominal pain, dysphagia, dyspepsia, diarrhea, constipation and bloating. These conditions were traditionally thought to have no explainable origin. However, recent clinical approaches consider that these conditions arise due to alterations in the gut-brain axis, which helps to explain why they are often associated with disruptions in other physiological systems and commonly associated with mood disturbances and decreased quality of life. FGID are differentiated into 33 different disorders in adults with altered bowel habits being one of the most common.2 FGID including constipation are associated with several co-morbidities including anxiety and depression.3

FGID Background

The cause of FGID is multidimensional and involves an interplay between the bidirectional dysregulation of the gut-brain interaction (the gut-brain axis), alterations in GI motility, visceral hypersensitivity, altered microbiota, increased intestinal permeability, low grade infiltration and altered central nervous system processing of sensory input.4 The interplay of these symptoms can significantly impact quality of life in many dimensions of health including social, emotional, physiological etc. Therefore, management needs to take this same multidimensional approach.5 Unfortunately, treatment is often focused on one condition such as constipation, or the disturbance in mood, rather than considering the interrelationship of the issues. For example, laxatives, stool softeners, fibers, prebiotics and probiotics are often used to manage constipation.6 While they may successfully improve bowel function, they are associated with side effects when used long term and they do not address the co-related conditions. Therefore, nutraceuticals which could address the co-related conditions of gastrointestinal health along with alterations in stress, sleep, mood and feelings of anxiety would be advantageous.

The Combination of Withania somnifera and Abelmoschus esculentus

A combination of W. somnifera (ashwagandha) and A. esculentus (okra), which have been shown to work synergistically to stimulate peristalsis and improve barrier function. This combination (as Digexin) has demonstrated adaptogenic function and has been shown to Increase serotonin. In a proof of concept randomized, double-blind, placebo-controlled study,7 48 adult men and women with functional constipation received either 300 mg, or 500 mg of a botanical blend or placebo for 14 days. Participants receiving both doses of the supplement experienced a significant reduction in patient reported constipation symptoms, improved in quality of life, improvement on the Gastrointestinal Symptom Rating Scale (GSRS) scores, improved sleep quality and reduced stress. At the end of the study subjects showed significant increases in serum serotonin, gastrin and interleukin-10 and decrease in interleukin-6 and cortisol levels. No adverse events were reported. A similar unpublished study of 135 men and women receiving the same doses for 60 days revealed that participants consuming both doses experienced a significant reduction in constipation and related symptoms, gastrointestinal symptoms, improved quality of life, bowel performance, anxiety, depression and sleep quality. They experienced a significant improvement in serotonin, gastrin, DAO and anti-inflammatory cytokines, decreased levels of serum cortisol, zonulin and pro-inflammatory IL-6. Improvements in the serotonin and gastrin indicate enhanced secretion of gastric mucus and peristalsis. There were no serious side effects.8 These findings support preclinical data in rats receiving the formulation for eight. The rats demonstrated improved bowel movements, gastric motility, reductions in corticosterone and increased serotonin which modulates GI motility.9

Traditional Benefits of Withania somnifera and Abelmoschus esculentus

The findings are supported by the known benefits of both the key ingredients. The traditional use of Withania somnifera (L.) Dunal (Solanaceae), also called “Indian winter cherry” or “Indian ginseng” for many conditions including stress, sleep and constipation. Extracts of W. somnifera have demonstrated neuroprotective and psychoacative activities in preclinical and human studies.10

Although less studies as a nutraceutical, okra (Abelmoschus esculentus L.), commonly known as lady’s finger, is known for the many health benefits associated with its consumption as a food. Different benefits are associated with different parts of the plant. Consuming the pod has been shown to improve the nervous system, brain, heart, stomach, muscle and intestinal function. It has traditionally been used for gastroprotective, and antiulcer benefits as well as for a diuretic.11 “The fruits are used as cooling, stomachic, astringent and aphrodisiac purposes and used in chronic dysentery, gonorrhea, urinary discharges, strangury and diarrhea.”12 It has demonstrated antioxidant and anti-inflammatory activities which may help to explain its role in many of the health benefits it is known for including its neuroprotective effects.12

Conclusion

The demonstrated bioactivities of W. somnifera and A. esculentus (as Digexin), have been shown to work synergistically to stimulate peristalsis and improve barrier function. This combination help to explain the results found in the preclinical and human clinical studies conducted on the combination of the two. The formula supports GI function, particularly bowel function and motility, while significantly impacting stress, sleep, feelings of anxiety and mood by impacting the gut and brain via the bidirectional connection between the two, called the gut brain axis thereby significantly impacting quality of life in multiple dimensions of health. The formula represents a whole patient approach to health by supporting multiple dimensions of health and well-being via the gut-brain axis. NIE

References

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2 Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology 2016;150:1262– 79.e2.

3 Petersen MW, Schroder A, Jorgensen T, et al. Irritable bowel, chronic widespread pain, chronic fatigue and related syndromes are prevalent and highly overlapping in the general population: DanFunD. Sci Rep 2020;10:3273.

4 Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: advances in understanding and management. Lancet 2020;396:1664–74.

5 Fikree A, Byrne P. Management of functional gastrointestinal disorders. Clin Med (Lond). 2021 Jan;21(1):44-52. doi: 10.7861/clinmed.2020-0980. PMID: 33479067; PMCID: PMC7850201.

6 Basilisco G. Patient dissatisfaction with medical therapy for chronic constipation or irritable bowel syndrome with constipation: Analysis of N-of-1 prospective trials in 81 patients. Aliment Pharmacol Ther 2020;51(6):629–36.

7 Punukollu RS, Chadalawada AK, Siddabattuni K, Gogineni NT. 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.

8 Dixit I, Singh G. A randomized, double-blind, placebo-controlled study to evaluate the efficacy and tolerability of a novel herbal composition to relieve constipation and to improve bowel clearance in healthy subjects. (unpublished).

9 Unpublished preclinical data.

10 Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M, Saha SC, Patil MT, Kandimalla R, Proćków J, Dey A. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomed Pharmacother. 2021 Nov;143:112175. doi: 10.1016/j.biopha.2021.112175. Epub 2021 Sep 27. PMID: 34649336.

11 Elkhalifa AEO, Alshammari E, Adnan M, Alcantara JC, Awadelkareem AM, Eltoum NE, Mehmood K, Panda BP, Ashraf SA. Okra (Abelmoschus Esculentus) as a Potential Dietary Medicine with Nutraceutical Importance for Sustainable Health Applications. Molecules. 2021 Jan 28;26(3):696. doi: 10.3390/molecules26030696. PMID: 33525745; PMCID: PMC7865958.

12 Islam MT. Phytochemical information and pharmacological activities of Okra (Abelmoschus esculentus): A literature-based review. Phytother Res. 2019 Jan;33(1):72-80. doi: 10.1002/ptr.6212. Epub 2018 Oct 22. PMID: 30346086.

Douglas S. Kalman PhD, RD, FACN, FISSN is a clinical associate professor in the Dr. Kiran C. Patel College of Osteopathic Medicine at Nova Southeastern University in Fort Lauderdale, FL. Kalman is also co-founder and co-director along with Dr. Susan Hewlings of Substantiation Sciences, a strategic nutrition business consultancy. Additionally, Kalman was a co-founder of the International Society of Sports Nutrition (ISSN). Most recently, he served as the senior vice president of scientific and regulatory affairs for the Natural Products Association (NPA). Earlier in his career, Kalman was the VP of Scientific Affairs for Nutrasource, a nutrition-centric Contract Research & Service Organization. He has worked six Olympic games and with a multitude of teams and individuals on the collegiate and professional sport levels. He has been involved in more than 400 clinical trials and projects within the pharmaceutical, medical and exercise – nutrition fields. Kalman has published more than 100 peer-reviewed manuscripts, more than 100 abstracts/poster sessions and has authored or co-authored five academic textbooks.