May 20, 2020

Healing the Gut Naturally

An intervention study shows gastrointestinal benefits of natural agents
A combination of natural agents long used by natural-medicine practitioners gets some evidence-based validation in a new intervention study.

This article is part of our May 2020 special issue. Download the full issue here.


Ried K, Travica N, Dorairaj R, Sali A. Herbal formula improves upper and lower gastrointestinal symptoms and gut health in Australian adults with digestive disorders. Nutr Res. 2020;76:37-51.


To determine whether a combination of natural agents for gut health is tolerable and effective in adults with gastrointestinal symptoms


Single-arm study using differing doses of intervention over 3 consecutive 4-week periods


Participants received a sachet of the following combination of ingredients (Table 1 from publication under review here; the abbreviation NC stands for “nutrition care”):

Table 1. Ingredient composition of each 5 g (1 sachet) of the NC Gut Relief Formula

Ingredients Per 5-g sachet 
Curcuma longa rhizome as CumeroneTM 30.37 mg 
 Equiv. Curcumin 6.38 mg
Glutamine 2.5 g 
Quercetin 200 mg 
Glucosamine hydrochloride 500 mg 
 Equiv. Glucosamine 415.05 mg
A vera (inner leaf/gel without latex & rind) 2.5 mg 
 Equiv. A vera leaf fresh 500 mg
 Equiv. Aloe polysaccarides 187.5 mg
 Equiv. Aloin (as barbaloin) 0.2 μg
Ulmus rubra (slippery elm) bark powder 500 mg 
Guar gum 100 mg 
Pectin 100 mg 
Peppermint Oil 3 mg 
Dibasic sodium diphosphate 260 mg 

Equiv, equivalent. Reprinted under Creative Commons 4.0 license.

As noted in the table, this formulation comprised single-serving sachets of 5 grams each. The researchers asked participants to mix this with water or with food. They assessed compliance by questionnaire as well as sachet count at the end of each visit.

Total study time was 16 weeks, with the first 4 weeks (month 0) used as a control period to establish baseline symptoms. During the first intervention phase (month 1), participants consumed a single sachet of the formulation daily for 4 weeks. In the second intervention phase (month 2), participants consumed 2 sachets daily for 4 weeks. For the third and final intervention phase (month 3), participants were able to choose their preferred dose: 0, 1, or 2 sachets daily. During month 3, there were 2 participants who chose not to take the formula, 13 participants who chose to take 1 sachet daily, and 28 participants who continued to take 2 sachets daily.


A total of 43 adults, all with gastrointestinal (GI) symptoms, completed the study. All but 1 participant had lower GI symptoms (n=42). Most participants also had upper GI symptoms (n=32). The average age was 50 years, and 75% were women.

All participants (N=43) completed the questionnaires at all time points.

Nearly all participants (n=42) completed intestinal permeability testing at week 4 (baseline) and week 16 (study end).

Stool analysis at weeks 4 and 16 was completed in 86% of participants (n=37).

One-third of the participants with upper GI symptoms (11 out of 32) were taking a proton pump inhibitor (PPI) at the start of the study.

Outcome Parameters

This study used both subjective and objective outcome parameters.

Subjective outcome parameters

The researchers used measurements at the end of the baseline period, which is also the start of month 1, as baseline symptoms.

Participants completed validated questionnaires at the start of the study and at the end of each month of the study.

Upper GI symptoms were assessed using:

  • Leeds Short-Form Dyspepsia Questionnaire
  • GERD-Q Questionnaire
  • GERD QoL Questionnaire
  • GERD-HRQL Questionnaire

Lower GI symptoms were assessed using:

  • Bristol Stool Chart
  • Birmingham IBS Symptom Questionnaire
  • IBS-QoL Questionnaire

Researchers assessed other symptoms such as fatigue, mouth ulcers, nervousness, rashes, and palpitations by questionnaire as well. They also assessed pain severity, type, location, and history using a 10-point visual pain scale.

Objective outcome parameters

The researchers took objective measures at baseline (end of month 0) and at the end of the study (end of month 3). These included:

  • A Helicobacter breath test
  • Gut microbial profiles using polymerase chain reaction
  • Assessment of intestinal permeability using lactulose/mannitol (L/M) urine testing
  • Blood tests to assess tumor necrosis factor-alpha, interleukin (IL)–1beta, IL-6, and IL-8

Key Findings

Baseline symptoms did not vary significantly during the control period of 4 weeks (month 0); therefore, baseline symptomology was considered consistent without intervention. Baseline measurements used for comparison in the study were established at week 4 (the start of month 1).

Overall, the intervention significantly improved the frequency and severity of upper and lower GI symptoms (including indigestion, heartburn, nausea, constipation, diarrhea, abdominal pain, and troublesome flatulence) by 60% to 80%. It also improved physical functioning, energy levels, mood, and sleep 60% to 80% from baseline values.

Specifically, after 12 weeks of intervention, intestinal permeability significantly improved, from 53% of participants having normal L/M ratios at baseline to 90% of participants at week 16 (P<0.001). This did not correlate to the number of sachets consumed. Participants on PPIs (n=11) were reported to have a slightly smaller improvement in intestinal permeability than those not taking PPIs (paper did not show data).

The participants with normal or hard stools had a better chance of normalizing their intestinal permeability with the formula. Of the participants who had high intestinal permeability at baseline, all of those who had normal stool, 90% of those who had hard stool, and 66% of those with soft stool had normalized intestinal permeability at the end of the study.

Overall, the intervention significantly improved the frequency and severity of upper and lower GI symptoms by 60% to 80%.

Nearly half of the participants who began the study on a PPI (n=11) no longer needed it at the end of the study. Given the low number of participants taking a PPI, statistical significance was not achieved.

Over the course of the study, many of the participants were able to reintroduce foods they did not tolerate prior to the intervention, including but not limited to: fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) foods such as garlic, onion, and beans; spicy foods; acidic foods (eg, tomatoes and citrus foods); and caffeine.

Gut microbial commensal bacteria increased, in particular Clostridium spp, Lactobacillus spp, and Faecalibacterium prausnitzii. These all benefit immune and gut health.

The majority of the participants tolerated the formula well, with 93% finding it easy to take. Taste was favorable in 45%, with 37% reporting neutral feelings about taste and 7% disliking it completely.

Practice Implications

Unlike so many studies that are designed to use a single herb or constituent for a specific sign or symptom, this study used a generalized formula for a wide variety of GI complaints. The study also used agents that are familiar to practitioners of natural medicine. That such a simple, cost-effective combination can be broadly applicable has appeal from a practical perspective. It is also nice to see a study using a formulation designed to heal the gut, rather than merely reduce symptoms. This formulation represents a typical naturopathic protocol, where the goal is to enhance the body’s ability to heal itself.

The formulation used in this study follows a logical combination of diverse gut-supportive natural agents. While there are many gut formulas available, those meant to correct gut permeability are likely to contain demulcent plants (eg, slippery elm, marshmallow root), immune-supportive polysaccharides (eg, aloe vera inner leaf, arabinogalactans), prebiotics and/or synbiotics (eg, pectin, guar gum), anti-inflammatories (eg, curcumin, quercetin, chamomile), and the amino acid glutamine, which is well known as a preferred carbon source for enterocytes.

Pancreatic or brush border enzymes are commonly added to a gut-healing formula to relieve symptoms while the gut heals. The current study under review did not use enzymes in any form. Also, regardless of the details of any gut-healing supplement protocol, patients generally follow the protocol alongside a simple diet that removes foods and beverages that may damage the mucosal lining (eg, high-sugar foods, alcohol, foods to which the patient is sensitive or allergic, etc.).

Each of the ingredients used in this study’s formulation has prior evidence suggesting relief of GI symptoms when taken individually. The authors contend that this is the first study to combine these proven natural agents into 1 serving. Presumably the ease of use allows for better compliance than taking each agent separately. In contrast, taking the combination as single agents would allow for some individualization at the discretion of the prescriber. Regardless of how it is delivered, the formulation used in this study is a good representation of a typical protocol, and the results are in keeping with clinical observation.

Curcumin, which has been shown to reduce IBS symptoms in an 8-week trial,1 has several gut-specific actions including stimulating bile secretion (ie, cholagogue effect), promoting healthy gut microflora, and improving wound healing through its anti-inflammatory action.2 Quercetin has also been shown to affect the gut microbiota, often in concert with fiber in the diet.3,4 Glucosamine hydrochloride also has beneficial effects on the gut flora.5 Slippery elm bark is a classic herbal demulcent, often used when soothing of the throat or gut is therapeutically indicated. In one study that used a combination of natural agents including slippery elm, symptoms of constipation-predominant IBS were significantly improved.6

Pectin and guar gum have each been proven beneficial to gut health and lessening of GI symptoms.7,8 During the final 4-week phase of the current study under review, most of the participants with loose stool chose to continue the higher dose of the intervention. The authors speculated that this may be due to noticeably better stool-firming effect from higher doses of soluble fibers. In addition to the bulking effects, guar gum has been shown to increase Lactobacillus and Bifidobacterium, which led to an improvement in quality of life in IBS patients in 1 study.8

Aloe vera gel, or aloe vera inner leaf, is traditionally used for stomach complaints of all kinds. It is hepatoprotective, antiulcerative, and anti-inflammatory.9 In 1 small study of 79 patients with gastroesophageal reflux disease (GERD), aloe was able to reduce symptoms of reflux as effectively as the medications omeprazole or ranitidine.10 It is essential to note that the study currently under review used the inner leaf only. The latex, or outer leaf, contains the potent laxative emodin. This should be avoided unless a laxative effect is desired. No matter how many times this is stressed, inevitably some people will take a whole-leaf product and have loose stools or even diarrhea. Fortunately, this is easily remedied by swapping the whole-leaf product for one using inner leaf only.

Peppermint oil is an interesting addition to this formula. There is good evidence for its use in IBS. A meta-analysis of 16 clinical trials involving 651 participants concluded that peppermint oil significantly reduced symptoms of IBS (P<0.005).11 However, among the many constituents of peppermint oil is menthol, a potent phenolic that gives peppermint its distinct scent. Menthol is commonly found in topical creams for sore muscles due to its antispasmodic effects. In keeping, relaxing smooth muscles of the GI tract on contact may have a therapeutic or untoward effect.

The relaxation upon menthol’s contact with muscle can elicit reflux symptoms in some people when the muscle of the lower esophageal sphincter is relaxed.9 Conversely, menthol may have a therapeutic role in relieving diffuse esophageal spasm.12 While reflux may be a concern, the current study under review did not report any worsening of reflux in participants with or without GERD. Also, as with any essential oil taken orally, direct irritation of the stomach lining is a risk. Whether it is the adsorption of the peppermint oil to the fibers in the formula or whether the dose (3 mg) was so small that there were no side effects, it appears the peppermint oil did not adversely affect any participants in the current study.

To be clear, peppermint oil is considered therapeutic for gut health as an antispasmodic, an antimicrobial, and an anti-inflammatory, and its role in this formula does follow prior evidence.13 For example, peppermint oil has been shown to speed gastric emptying in a small trial of 10 healthy volunteers, which may be therapeutic for some.14 The Canadian Gastroenterology Association has recommended peppermint oil as part of initial therapies for IBS, prior to beginning prescription drugs in patients.15 Peppermint has also been used traditionally for stomach complaints of various kinds. The 2 forms that are least likely to cause any side effects are peppermint leaves as tea and enterically coated oil of peppermint, which does not dissolve in the stomach. Some studies have demonstrated that enterically coated peppermint oil can reduce pain from IBS.16

According to the average scores of participants reporting upper GI symptoms, there was significant improvement in nearly every parameter on the upper GI questionnaires. Almost half of those taking a PPI were able to go off of their drug by the end of the 4-month study. There was no notation of how long these participants had been taking their PPIs, but experience dictates that the longer a person has been taking an acid-blocking agent, the longer it takes to get off it. The rebound effect of sudden acid production in a stomach that lacks a proper mucosal barrier from extended PPI use can induce symptoms of gastritis. All practitioners should proceed with caution when a patient chooses to go off a PPI, particularly those who may not have proper sensory innervation to their stomach (eg, diabetics, the elderly). The populations at high risk for dysplasia and cancer should also approach discontinuation with caution, if at all. That said, when patients can safely discontinue PPIs, they, in partnership with their practitioners, should pursue this since the PPIs have been associated with lower-bowel dysfunction, including small intestinal bacterial overgrowth (SIBO).17

The use of objective measures of intestinal permeability and stool microbiology strengthened the findings of this study. Given the subjectivity of symptoms, such objective measures remove the risk of bias, particularly in studies such as this one where there is no control arm for comparison. Since this is the first study of its kind, repeating these results with a larger cohort and adding a conventionally treated arm would provide a higher level of evidence as well as a “real world” scenario for treatment.

The lesson is not in the novelty of the agents used in this study. This study does not bring any new or exotic constituent to light. To the contrary, this study validated the use of familiar natural agents commonly used by integrative practitioners and traditional healers alike. Empirical usage of many natural treatments continues in lieu of evidence due to their efficacy, which requires success a good amount of the time to be noticeable. Therefore, the high success rate of this gut formula is not surprising, nor are the study results suspect. Unfortunately, many studies are done on singular natural agents or plant constituents in search of a definitive mechanism of action, which does not represent traditional or modern natural medicine practices. More studies using combinations of natural agents that mimic current practices are needed if practitioners are expected to use evidence-based natural medicine effectively.

Categorized Under


  1. Bundy R, Walker AF, Middleton RW, Booth J. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise healthy adults: a pilot study. J Altern Complement Med. 2004;10(6):1015-1018.
  2. Peterson CT, Vaughn AR, Sharma V, et al. Effects of turmeric and curcumin dietary supplementation on human gut microbiota: a double-blind, randomized, placebo-controlled pilot study. J evidence-based Integr Med. 2018;23:2515690X18790725.
  3. Tamura M, Hoshi C, Kobori M, et al. Quercetin metabolism by fecal microbiota from healthy elderly human subjects. PLoS One. 2017;12(11).
  4. Combet E, Edwards CA, Alkhaldy AA. Colonic metabolism of the common dietary polyphenol quercetin-3-O-rutinoside (Rutin)–impact of age and gut health. FASEB J. 2016;30(1_supplement):611-690.
  5. Navarro SL, Levy L, Curtis KR, Lampe JW, Hullar MAJ. Modulation of gut microbiota by glucosamine and chondroitin in a randomized, double-blind pilot trial in humans. Microorganisms. 2019;7(12):610.
  6. Hawrelak JA, Myers SP. Effects of two natural medicine formulations on irritable bowel syndrome symptoms: a pilot study. J Altern Complement Med. 2010;16(10):1065-1071.
  7. Xu L, Yu W, Jiang J, Feng X, Li N. Efficacy of pectin in the treatment of diarrhea predominant irritable bowel syndrome. Zhonghua wei Chang wai ke za zhi= Chinese J Gastrointest Surg. 2015;18(3):267-271.
  8. Giannini EG, Mansi C, Dulbecco P, Savarino V. Role of partially hydrolyzed guar gum in the treatment of irritable bowel syndrome. Nutrition. 2006;22(3):334-342.
  9. Hatlebakk JG, Berstad A. Pharmacokinetic optimisation in the treatment of gastro-oesophageal reflux disease. Clin Pharmacokinet. 1996;31(5):386-406.
  10. Panahi Y, Khedmat H, Valizadegan G, Mohtashami R, Sahebkar A. Efficacy and safety of Aloe vera syrup for the treatment of gastroesophageal reflux disease: a pilot randomized positive-controlled trial. J Tradit Chinese Med. 2015;35(6):632-636.
  11. Grigoleit H-G, Grigoleit P. Peppermint oil in irritable bowel syndrome. Phytomedicine. 2005;12(8):601-606.
  12. Parvataneni S, Vemuri-Reddy SM. Role of peppermint oil in diffuse esophageal spasm in the geriatric population. Cureus. 2020;12(3).
  13. Oldfield EC, Copare J, Da J. Peppermint Oil: Clinical Uses in the Treatment of Gastrointestinal Diseases. Vol 3.; 2015.
  14. Inamori M, Akiyama T, Akimoto K, et al. Early effects of peppermint oil on gastric emptying: a crossover study using a continuous real-time 13 C breath test (BreathID system). J Gastroenterol. 2007;42(7):539-542.
  15. Moayyedi P, Andrews CN, MacQueen G, et al. Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS). J Can Assoc Gastroenterol. 2019;2(1):6-29.
  16. Weerts ZZRM, Masclee AAM, Witteman BJM, et al. Efficacy and safety of peppermint oil in a randomized, double-blind trial of patients with irritable bowel syndrome. Gastroenterology. 2020;158(1):123-136.
  17. Compare D, Pica L, Rocco A, et al. Effects of long-term PPI treatment on producing bowel symptoms and SIBO. Eur J Clin Invest. 2011;41(4):380-386.