DGL: Independent Evidence on Digestive Symptoms and Safety

Key takeaways

• DGL is a licorice extract with glycyrrhizin reduced or removed. The name does not establish a uniform composition or zero residual glycyrrhizin
• GutGard is one flavonoid-rich proprietary preparation. Its trials cannot establish that all DGL tablets, teas or blends work alike
• Positive dyspepsia and reflux trials have manufacturer involvement. A dependable, independently established digestive benefit remains unproven under this review's funding screen
• Older ulcer trials include null results and multi-ingredient products. A DGL-containing antacid combination cannot establish the effect of DGL alone
• DGL has not been independently established as a replacement for H. pylori eradication treatment, ulcer care or reflux medicines
• Reducing glycyrrhizin addresses an important source of licorice toxicity, but does not establish complete cardiovascular or medication safety for every product

DGL has a plausible rationale and some encouraging short-term human results, especially for the proprietary extract GutGard. The main positive studies are commercially involved, while other studies use different extracts, combinations or incomplete funding disclosures. Confidence is low in a generalizable independent benefit for dyspepsia, reflux, ulcer healing or H. pylori eradication. Confidence is high that these formulations must be distinguished and that a “DGL” label alone cannot guarantee safety. The funding limitation does not prove that DGL is ineffective.

Contents

Evidence summary · What it is · Forms and grades · How it works · Hype versus evidence · Benefits by claim · What works · Risks · Interactions · Who should avoid · Studied doses · Laboratory evidence · Funding · Regulation · FAQs · Sources

Evidence summary

The strength column concerns the exact claim after conflict screening. Commercial outcome studies are retained as context, including their favorable findings, but excluded from the independent benefit basis. Unknown funding or purchasing arrangements remain unknown.

What it is

Licorice, also spelled liquorice, comes from plants in the genus Glycyrrhiza. Commercial materials can involve different species, roots, underground stems and extraction processes. Chemical profiling can distinguish major species and measure several constituents; the plant name alone is an incomplete product specification. Li's analytical study

Deglycyrrhizinated licorice describes processing intended to reduce glycyrrhizin, also called glycyrrhizic acid. Glycyrrhizin is a sweet-tasting saponin associated with licorice's important electrolyte and blood-pressure risks. A reduced-glycyrrhizin extract can still contain biologically active flavonoids and other compounds. Removing one component does not make the remaining mixture pharmacologically inert. NCCIH licorice overview

This article concerns oral DGL and closely relevant reduced-glycyrrhizin extracts used for digestive claims. It does not transfer findings from licorice mouthwashes, skin preparations or unrelated indications to the stomach or bowel.

Forms and grades

The chemical distinction for carbenoxolone is described in the EMA assessment. Historical Caved-S advertising lists DGL with aluminium hydroxide, magnesium carbonate and sodium bicarbonate; earlier material also lists bismuth and frangula. These are manufacturer-origin ingredient records, not independent efficacy evidence. 1983 label advertisement, 1979 label advertisement

A specification discrepancy that matters

The 2012 and 2013 GutGard papers specify glycyrrhizin at no more than 0.5% by weight. The 2025 reflux paper instead states no more than 3.0%, while the current manufacturer webpage states below 0.5%. These published descriptions are not identical. This audit could not establish whether the later figure reflects a specification change, a reporting error or another explanation. A current batch certificate would be needed to establish actual content. 2012 methods, 2013 methods, 2025 methods, manufacturer specification

Useful product information includes the botanical species, extraction process, extract amount, measured residual glycyrrhizin, other active ingredients and batch testing. “Natural,” “clinical grade” and a trademark do not substitute for those details or demonstrate clinical benefit.

How it works

Proposed digestive actions include effects on mucus or mucosal protection, inflammatory signaling and bacterial activity. Much of this rationale comes from cell or animal experiments. For example, GutGard research in infected rodents examined gastric bacterial colonization; it did not test whether an adult taking a retail DGL tablet is cured of infection. Kim 2013 preclinical study

There are several distinct questions:

• Does the product reduce a person's symptoms?
• Does an ulcer actually heal on objective examination?
• Is an infection durably eradicated after treatment ends?
• Does any benefit persist without unacceptable adverse effects?

Evidence for one does not answer the others. A lower breath-test measurement, an anti-inflammatory laboratory signal or a short-term symptom improvement cannot establish all four.

The reason for reducing glycyrrhizin is also mechanistic: its metabolite can interfere with cortisol handling through 11β-HSD2, promoting mineralocorticoid-like effects. That helps explain the concern about sodium retention, potassium loss and blood pressure with glycyrrhizin-containing licorice. It does not identify a universal safe residual concentration for every person. Liu's pharmacological context

Hype versus evidence

A positive branded trial does not validate the whole category. GutGard, generic DGL, whole root and a licorice-containing blend are different interventions. Shared plant ancestry is not a clinical equivalence test.

A review's academic status does not erase a trial's commercial links. The 2023 Cochrane review's GutGard result comes from one small trial. Its study table records funding and conflicts as unavailable, yet also records company-generated randomization. The original paper supplies the manufacturer affiliations. Cochrane review

A “phase III” title does not itself mean a medicine has regulatory approval. Approval is a separate legal determination. Likewise, “no conflicts declared” is not equivalent to “no commercial support.”

“No side effects” or “no interactions” is too broad. Natural Remedies currently promotes long-term safety and absence of clinically relevant drug interactions; AIDP's sales sheet also makes barrier and motility claims. Those statements exceed what the short, formulation-specific human evidence can establish. These are commercial claims, not the verdict of this review. Manufacturer page, distributor sales sheet

Failure to find a significant difference does not prove two treatments equivalent. An equivalence or non-inferiority claim needs an appropriate design and margin. A small, inconclusive comparison cannot establish that an herbal product safely replaces a medicine.

Benefits by claim

Functional dyspepsia Insufficient independent evidence

The 50-person Raveendra trial reported better symptom and quality-of-life scores with GutGard than placebo after short treatment. Seven authors were affiliated with Natural Remedies, which developed the randomization sequence. The accessible report does not provide a complete cash-funding or procurement ledger. Direct manufacturer research involvement is enough to exclude the outcome from the independent benefit basis. Original trial

Cochrane's favorable assessment deserves to be reported, but it is a synthesis of that same study, not a second clinical replication. The review declared university support in Chile and Germany and no known author conflicts. Those disclosures strengthen transparency at review level without changing the underlying trial's provenance. Review methods and disclosures

The practical research gap is an adequately powered, independently financed trial with a defined extract, clinically meaningful response threshold and longer follow-up. It should also establish which dyspepsia population was studied rather than treating all upper-abdominal symptoms as one diagnosis.

Reflux and heartburn Insufficient independent evidence

Raj's 2025 trial randomized 200 adults. Baseline-adjusted reflux-related quality-of-life improvement favored GutGard; the unadjusted day-28 comparison did not. Only 78 active and 87 placebo participants contributed to that day-28 table. Gastric emptying did not improve between groups. The study was sponsored by Natural Remedies, with design/protocol input, although authors declared no conflicts. Trial

This is a worthwhile symptom signal, but it does not establish healing of erosive esophagitis, prevention of complications, benefit in severe disease or equivalence to acid-suppressing treatment. A questionnaire result and an objective disease outcome should not be merged into a “reflux cure” claim.

Gastric and duodenal ulcers Insufficient independent evidence

The older literature does not support a uniformly positive story. Engqvist's crossover study included 38 patients initially and found no faster gastric-ulcer healing. Feldman and Gilat's 47-person duodenal-ulcer trial tested Caved-S, a combination product, and found no advantage over placebo. This is evidence about that historical formulation, not every DGL extract. Full historical financing and procurement could not be verified from the accessible records, so neither is labeled clean independent evidence here. Engqvist 1973, Feldman 1971

Bardhan's 96-person gastric-ulcer trial found no benefit in healing or clinical improvement. Its full report acknowledges Boehringer Ingelheim's supply of Ulcedal and placebo. The wording does not establish whether these were bought or donated. The paper also describes earlier favorable small studies, including Turpie's, while questioning their methods and unusually low control healing. Primary report, archived in an FDA docket

Morgan's 100-person comparison found no significant healing difference between Caved-S and cimetidine. Caved-S was a multi-ingredient preparation, and the study was single-blind. A later 100-person trial found that adding Caved-S to ranitidine did not improve healing or symptoms. Historical funding remains unresolved. Neither establishes that isolated DGL is equivalent to modern care. Morgan 1982, Morgan 1985 add-on study

EMA's revised assessment, published in July 2026, judged DGL ulcer evidence conflicting and affected by serious methodological limitations, insufficient for well-established medicinal use. Its assessment of the small dyspepsia trial was also cautious. This is regulatory appraisal of mixed underlying evidence, not a new independently funded trial. EMA 2026 assessment

H. pylori Insufficient independent evidence

Puram's GutGard trial enrolled 107 people and analyzed 100 per protocol. At day 60, stool-antigen tests were negative in 56% versus 4%, and breath tests in 48% versus 2%. These were on-treatment assessments, without established durable post-treatment eradication. NICS in South Korea financed the project; Natural Remedies employees coauthored it. Its findings do not justify substituting DGL for eradication care. Puram 2013

Two Iranian studies require separate interpretation:

• Momeni 2014: 60 participants received antibiotic-containing regimens with either D-Reglis or bismuth. Eradication was 67% versus 57%, a nonsignificant difference. The authors' equivalence conclusion exceeds that comparison's design. Shahrekord University funded the work, but product purchasing terms and batch glycyrrhizin were unresolved. Primary study
• Hajiaghamohammadi 2016: adding D-Reglis to an antibiotic regimen yielded 83.3% versus 62.5% negative stool-antigen results among analyzed participants. Funding and procurement were not adequately described, and participant totals differ between the narrative and outcome table. This is preliminary adjunct evidence, not DGL-alone treatment. Primary study

Yoon's 2019 fermented-milk trial randomized 142 people to a probiotic/licorice combination or control. Despite favorable within-group changes, key between-group comparisons for breath-test values, symptoms and quality of life were not significant. The product was developed by Korea Yakult; no funding was declared, but purchasing terms were not given. The paper does not establish the intervention as the exact GutGard preparation. Primary report

Testing after appropriate treatment is important because symptom relief does not establish that infection is gone. NIDDK describes cause-directed ulcer treatment and follow-up testing for H. pylori; it does not establish a DGL replacement regimen. NIDDK ulcer treatment

Intestinal barrier repair and general gut health Insufficient

The audited evidence does not independently establish DGL as a treatment for IBS, constipation, inflammatory bowel disease or a broadly defined “leaky gut” condition. Nor does it establish that changes to bacteria or mucosal biology improve everyday health in people without a diagnosed problem.

Claims about general barrier repair should specify the population, validated measurement and patient benefit. A manufacturer's mechanism diagram or animal experiment cannot substitute for those clinical outcomes.

What works and what does not

Risks and reported side effects

Safety findings need the same scrutiny as benefits. Short studies in selected adults cannot estimate uncommon serious events, establish lifelong use or settle pregnancy safety.

NCCIH warns that glycyrrhizin-related serious effects can occur particularly with prolonged or high exposure and in susceptible people, including those with heart or kidney conditions or hypertension. Its cautious statement that glycyrrhizin-free oral products might be safe for up to four months is not a verified safe-use limit for every “DGL” label. NCCIH

The reflux trial's event record provides limited short-term context, not proof of complete safety. Raj 2025 safety table

Safety note: Vomiting blood or black, tarry stools requires urgent medical assessment. Food stuck in the oesophagus or inability to swallow saliva needs urgent care. Persistent vomiting, progressive swallowing difficulty or unexplained weight loss also requires prompt assessment. Sudden chest pain that does not go away, or chest pain with breathlessness, sweating or spreading pain, requires emergency assessment rather than an assumption that it is heartburn. NHS chest-pain guidance NIDDK reflux warning symptoms

Interactions and evidence gaps

There is no validated complete interaction list for every DGL preparation. The table distinguishes licorice-related concerns from the much narrower DGL-specific evidence.

EMA's licorice interaction assessment supports the electrolyte and blood-pressure concerns, while describing the limitations of anticoagulant reports. These warnings concern the preparations and exposures reviewed there; applying their exact risk to every DGL product would overstate the evidence. EMA interaction assessment, section 5.5.4

Liu's NIH-funded study had 14 healthy female completers and found no clinically relevant exposure changes for four probe-drug pathways after two weeks. The extract came from Natural Remedies through the university botanical center; purchase versus donation was not stated. The article did not identify it as GutGard. Its reassurance is limited to the tested extract, conditions and pathways, rather than all interactions. Human pharmacokinetic study

The actual label and medication list need review together. The available evidence does not support a universal spacing interval or instructions to stop, substitute or adjust prescribed treatment.

Who should avoid unsupervised use

Unsupervised use is particularly inappropriate when there is suspected bleeding, swallowing trouble, persistent unexplained symptoms, a known ulcer or confirmed H. pylori infection. A product that changes symptoms can leave the underlying cause untreated.

People with hypertension, heart or kidney disease, low potassium, a previous reaction to licorice products or complex medication regimens need product-specific assessment. Pregnancy, breastfeeding and childhood also lack an established general DGL supplement regimen in this review. These precautions are not a claim that every chemically verified low-glycyrrhizin preparation has the same risk as whole licorice.

Dosage and how to take

These are research descriptions, not instructions for personal use. Different extracts cannot be compared by milligram weight alone. Neither a trial dose nor a brand's serving size establishes an effective or safe regimen for another person or product.

Historical chewable-product research and modern capsule trials do not establish that chewing is superior to swallowing an otherwise equivalent preparation. Canada's specific licensing monograph does require chewable forms; that regulatory condition is described below. This audit did not find a convincing independent head-to-head test resolving the clinical comparison.

Animal and in vitro evidence excluded from conclusions

Kim's GutGard study used infected mice and gerbils. Korean institutional grants were declared; product procurement remained unclear. It supplies a biological hypothesis, not a human eradication result. Kim 2013

Bhide's 2022 safety report tested rats and included Natural Remedies R&D and regulatory-affairs authors. Its no-conflict declaration does not remove those affiliations. Animal tolerated doses are not converted here into a human safe dose, and the study is excluded from human safety conclusions. Bhide 2022

Laboratory evidence can help explain what to test next. It cannot establish relief, cure, prevention or an adverse-event rate in people. Human-derived cells outside the body also remain in vitro evidence.

Independent funding tracing

Who pays and who profits

Natural Remedies develops and sells GutGard. Its human-health site lists its Indian office in Bengaluru, a US office in Austin and manufacturing in Tamil Nadu, India. The company's leadership page identifies Anurag Agarwal as managing director and Amit Agarwal as a director and former R&D leader. These are documented operating roles; they are not verified current equity percentages. Product and locations, company leadership

The current ultimate shareholding and trust-beneficiary chain could not be established from an accessible current primary ownership filing. Older company-return material is insufficient to establish the 2026 cap table. This review therefore does not assign an ownership percentage to a named individual or invent an outside investor.

CARE Ratings' October 2025 credit report describes bank financing and loans from directors, relatives and other companies. It lists Natural Living as a wholly owned subsidiary at 31 March 2025. These are group financing facts, not evidence that any lender paid for a particular GutGard trial. CARE's issuer-fee business model makes it an interested corporate source, even though credit-market accountability gives it reasons to report accurately. Credit report and fee disclosure

AIDP in the United States currently offers GutGard in its own sales material. A manufacturer-origin announcement described an exclusive North American distribution arrangement historically. The current full licensing contract, territorial exclusivity and royalty terms were not verified. Distribution is not proof of equity ownership or research financing. AIDP sales sheet, manufacturer announcement

NICS, identified as a Seoul company in the 2013 trial, financed that project and had a coauthor. Its current beneficial ownership and exact relationship to the manufacturer were not verified. Likewise, the audited papers identify Iran Darouk and Korea Yakult as product businesses, but do not settle their study procurement terms or current ownership chains.

Public and nonprofit sources were checked too

The Cochrane review reports university support and no known author conflicts. The UK charity's 2024 accounts show that publication royalties from Wiley are its principal central revenue stream, with other products, events, consultancy and grants also contributing. Its policy restricts funding from businesses with a relevant health-topic interest. This supports a provisionally independent review-level classification, not automatic independence of every included trial. Review disclosures, Cochrane accounts and policy

NIH's NCCIH receives congressional appropriations. Public financing of the 2023 interaction study is documented, but the original extract transaction remains unresolved. Public cash and commercial product sourcing are separate questions. NCCIH funding history, trial disclosures

EMA and FDA have public mandates and accountability, but also agency-wide industry-fee income. That is disclosed as an institutional indirect tie. It does not establish that a DGL company paid for the particular guidance quoted here. EMA funding, FDA fee system

Money map

The arrows show documented roles, financing or product sources. A product-source arrow does not mean a donation. No ownership percentage is assigned where a current primary record was unavailable.

Plain-text version:

• Natural Remedies, India → develops and sells → GutGard
• Anurag and Amit Agarwal → documented leadership roles → Natural Remedies; no equity percentages inferred
• Natural Remedies → company authors and randomization → Raveendra dyspepsia research
• Natural Remedies → sponsorship and protocol input → Raj reflux research
• Natural Remedies → company coauthors → Puram H. pylori research
• NICS, South Korea → financial assistance and company coauthor → Puram research
• GutGard → commercial distribution → AIDP, United States; current contractual rights and royalties unresolved
• NIH, United States → public grants → Liu interaction study
• Natural Remedies → original extract source → Liu study; purchase or donation unresolved
• Shimadzu Scientific Instruments, United States → mass spectrometer provided → Liu study; terms unspecified
• Shahrekord University, Iran → declared funding → Momeni combination trial; purchasing terms unresolved
• Boehringer Ingelheim, Germany → acknowledged Ulcedal/placebo supply → Bardhan trial, United Kingdom; payment terms unresolved
• Natural Remedies → Natural Living, India; the credit report records 100% ownership at 31 March 2025, without identifying this as a GutGard trial-funding route

How this changes the verdict

Funding is not proof of a false result. However, manufacturer or seller outcome research does not count toward the independent benefit verdict used here. Unknown sponsorship is not automatically inferred from a branded product, and an arm's-length purchase would not itself be sponsorship. Missing procurement records are left as gaps.

The modern branded efficacy studies are concentrated in India, with additional relevant research in Iran, South Korea and older European settings. Nationality is not a quality score. Repeated manufacturer involvement, rather than country alone, is what limits independent corroboration.

Regulatory status

United States

Dietary supplements are not FDA-approved for safety or effectiveness before sale. A facility registration, lawful sale or food-use safety determination does not establish an approved treatment for ulcers, GERD or H. pylori infection. FDA distinguishes structure/function statements from disease-treatment claims, which bring a product within drug regulation. FDA supplement questions and answers

European Union

EMA published its revised licorice-root assessment and herbal monograph in July 2026. The assessment's traditional-use framework and its criticism of the clinical evidence must not be presented as a broad authorization for every DGL extract or branded digestive claim. The preparation and national product authorization matter. EMA document record, 2026 assessment

Canada

Health Canada's DGL monograph, dated 31 January 2025, supports a natural-health-product licensing route for specified demulcent digestive claims. It requires chewable forms mixed with saliva. Its specification allows no more than 3% of the original quantity of glycyrrhizic acid in the source material. That is different from a limit of 3% by weight of the finished extract. The monograph is industry licensing guidance, explicitly not a comprehensive evidence review. Canadian DGL monograph

This regulatory route does not establish an independently replicated treatment effect under this article's stricter evidence screen. Health Canada's institutional funding includes public appropriations and regulatory revenues. Departmental financial statements

This summary does not establish the status of every product in every jurisdiction. A clinical paper, trademark and regulatory authorization answer different questions.

Frequently asked questions

Does DGL mean completely glycyrrhizin-free?

Not necessarily. Published preparations are described with residual limits, and the GutGard reports themselves contain differing specifications. The useful information is the tested content of the particular extract and batch.

Is GutGard the same as generic DGL?

GutGard is a specific proprietary preparation. A generic DGL product should not inherit its study results without evidence of relevant compositional and clinical equivalence.

Does an improvement in heartburn prove an ulcer or infection has healed?

No. Symptoms, tissue healing and infection status are separate outcomes. Each requires the appropriate assessment.

Why does the verdict remain uncertain despite positive trials?

The positive findings are reported, but major studies have commercial involvement. This review deliberately asks what is established after excluding those outcomes from its independent benefit basis. Remaining unknown funding and formulation differences also matter.

Can DGL replace a PPI, antibiotics or bismuth?

The audited evidence does not establish that replacement. It does not support changing a prescribed regimen based on these supplement studies.

Must DGL be chewed?

Canada's cited licensing monograph requires chewing. Different clinical research programs used different formulations, and a convincing independent head-to-head comparison was not identified. Regulatory directions and evidence of comparative efficacy are separate questions.

Is it safe with every medicine if glycyrrhizin is low?

That has not been demonstrated. The human interaction study examined four metabolic pathways for one extract under short, controlled conditions. Residual glycyrrhizin and other constituents still require attention.

Sources and funding notes

Tier 1 means no identifiable subject-related stake after the stated checks; Tier 2 means indirect ties; Tier 3 means an interested party; Tier 4 means maker/seller production, sponsorship or demonstrated in-kind support. Unknown is not forced into a tier. Grades A–D describe credibility for the stated use: A high, B solid with limitations, C materially interested, D directly self-interested. These judgments describe provenance and incentives, not a guarantee that any result is true or false.

Scope and remaining gaps

This is a focused critical review, not a registered exhaustive systematic review. Historical full-text access was uneven; several old outcome records were verified through primary abstracts and indexed original reports rather than a complete financing archive. Missing grants, procurement terms, raw data, batch certificates, current beneficial owners and distribution contracts remain unresolved. Neither absence of disclosure nor a no-conflict sentence was treated as proof of independence or misconduct.

Last reviewed: 1 October 2026.

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