A peptic ulcer is a sore in the lining of the stomach, where it is called a gastric ulcer, or the first part of the small intestine, called a duodenal ulcer. In the United States, roughly 4.5 million people suffer from peptic ulcer disease.

Fortunately, integrative interventions including deglycyrrhizinated licorice (DGL), zinc-carnosine, and Lactobacillus reuteri have powerful ulcer-healing effects.

Causes and Risk Factors

• H. pylori infection, the primary cause
• Non-steroidal anti-inflammatory drugs (NSAIDs), the second-leading cause
• Stomach acid
• Alcohol
• Cigarette smoking

Symptoms

• Up to 40% of those with ulcers have no symptoms
• A gnawing or burning pain , nausea, vomiting, or heartburn

Complications

• Bleeding internally, which is the most common complication.
• Perforation, in which ulcers break through the wall of the duodenum or stomach.
• Note: This is a medical emergency requiring surgical intervention.

Diagnosis

• Upper gastrointestinal endoscopy, a camera inserted on a long tube down to the stomach, is necessary for a conclusive diagnosis of peptic ulcer. Endoscopy allows inspection and biopsy of the stomach and duodenum and detection of H. pylori.
• A CBC and stool occult blood tests are recommended for patients suspected of having a bleeding ulcer.

Conventional Treatment

• H. pylori-positive ulcers
• Antibiotics result in a 70‒90% cure rate.
• Note: Antibiotic resistance is a growing problem in Canada and the United States.
• Proton-pump inhibitors (PPIs) block the secretion of stomach acid, allowing ulcers to heal and often relieving pain.
• Note: When used long-term, PPIs are associated with a wide range of serious side effects including kidney and cardiovascular disease.
• Triple-therapy is a standard treatment that combines two antibiotics and a PPI. Bismuth may also be included for “quadruple therapy.”

• H. pylori-negative ulcers
• NSAID use should be discontinued. Antacids and medications that reduce acid secretion are used in these situations.
• Misoprostol (Cytotec) and sucralfate (Carafate) are used to help protect the stomach lining against the damaging effects of NSAIDs in patients who must continue to take them.

Novel and Emerging Strategies

• Silver nanoparticles. Laboratory and animal studies indicate silver nanoparticles have anti-H. pylori activity.
• Note: Silver nanoparticles should not be confused with over-the-counter colloidal silver preparations. Colloidal silver has not been proven effective for treating any condition, and may have several side effects, including argyria—a disorder in which the skin takes on a permanent bluish-gray discoloration.
• Liposomal linolenic acid. Liposomal linolenic acid has been shown to kill H. pylori and markedly reduce its population in the stomach of mice. In addition, liposomal linolenic acid was shown to decrease levels of pro-inflammatory cytokines triggered by H. pylori.

Dietary and Lifestyle Considerations

• A diet rich in fruits, vegetables, and fiber may reduce the risk of ulcers by 50%, and also help heal existing ulcers.
• Fermented dairy products such as yogurt and kefir appear to promote H. pylori eradication.
• Stress management is important as stress and tension is correlated with gastric and duodenal ulcers.

Integrative Interventions

• Deglycyrrhizinated licorice (DGL). In a trial, 100 patients who tested positive for H. pylori were treated with DGL or placebo for 30 days. At the end of the treatment period, 56% of the DGL group and 4% of the placebo group tested negative for H. pylori.
• Zinc-carnosine. In a randomized clinical trial, 86% of subjects treated with triple therapy alone achieved eradication while 100% treated with triple therapy plus zinc-carnosine (150 mg twice daily) were H. pylori-negative four weeks after treatment.
• Lactobacillus reuteri. L. reuteri DSM17648 supplements have been shown to decrease the H. pylori load in healthy H. pylori-positive individuals, and may thus prevent future H. pylori-associated problems, including the need for antibiotic treatment.
• Lactoferrin. A meta-analysis examined five randomized controlled trials that evaluated whether lactoferrin treatment was effective for H. pylori eradication. Those who received lactoferrin had more than 2.2-fold higher odds of eradication compared with controls.
• Flavonoids/polyphenols. Evidence from numerous studies indicate polyphenols, including flavonoids, hold promise in the prevention and treatment of peptic ulcers. Extracts from tea, apples, pomegranate, and grape seed are especially good sources of polyphenols with possible anti-ulcer and anti-H. pylori activity.

A peptic ulcer is a sore in the lining of the stomach or the first part of the small intestine. Ulcers in the stomach are called gastric ulcers, and those in the upper small intestine are called duodenal ulcers. Symptoms include pain, nausea, vomiting, and heartburn; in serious cases, ulcers may cause bleeding into the stomach or perforation of the gastrointestinal wall (Ferri 2016; DiMarino 2016a; Kuipers 2012).

In the United States, roughly 4.5 million people suffer from peptic ulcer disease, and about 500,000 new cases are reported each year (Ferri 2016; Anand 2017).

The most common causes of peptic ulcers are infection with the bacterium Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (Kuipers 2015).

Uncomplicated ulcers associated with H. pylori infection are usually treated with antibiotics plus a proton-pump inhibitor (PPI), which reduces gastric acid secretion and allows the ulcer to heal. Treatment of bleeding ulcers may require endoscopic surgery (Kuipers 2015; Lee 2013).

Increasing use of antibiotics in children over the past several decades has led to a decline in the prevalence of H. pylori infection among younger generations, and combination therapy with antibiotics and PPIs is very effective in treating peptic ulcers (Malfertheiner 2009; Kuipers 2012). However, antibiotic resistance now represents a critical factor in the failure of ulcer treatment (Homan 2015; Yaxley 2014). Thus, new methods for eradicating H. pylori and treating ulcers are needed.

The good news is that new scientific discoveries may improve the efficacy of ulcer treatment. For instance, integrative interventions including deglycyrrhizinated licorice (DGL), zinc-carnosine, and vitamin C have powerful anti-H. pylori and ulcer-healing effects (Puram 2013; Watari 2013; Pal 2011). Probiotics, particularly a strain called Lactobacillus reuteri DSM17648, appear to help control H. pylori and reduce the inflammatory response to infection with this organism. Treatment with probiotics can also enhance the ability of antibiotics to eliminate H. pylori infection, while reducing drug side effects (Boltin 2016; Homan 2015; Holz 2015).

In addition, lifestyle and dietary changes can have a profound impact on ulcer risk and promote ulcer healing. Smoking cessation, stress reduction, and avoidance of NSAIDs and excess alcohol all help promote ulcer healing and prevent recurrence (Lee 2013; Han 2002; Ferri 2016). A diet rich in fiber and plant phytonutrients called polyphenols can protect against development of peptic ulcers as well (Farzaei 2015; Ryan-Harshman 2004).

In this protocol, you will learn about the causes of peptic ulcers and how they are typically treated. Several emerging treatment techniques will be reviewed, and a number of dietary and lifestyle changes that may reduce ulcer risk will be discussed. In addition, many natural integrative interventions that may help keep the gastric and intestinal mucosa healthy will also be reviewed.

The lining of the stomach and intestine is covered by a thick mucus layer that functions as a physical barrier between the outside environment and the body (Chai 2011). The formation of peptic ulcers results from disruption of the mucosal barrier by factors such as stomach acid, pepsin, H. pylori infection, non-steroidal anti-inflammatory drugs (NSAIDs), alcohol, and cigarette smoking (Ferri 2016).

Gastric ulcers develop in the lining of the stomach. Pain from a gastric ulcer may be aggravated or alleviated by eating. Duodenal ulcers form in the first few centimeters of the lining of the duodenum (the upper part of the small intestine). Pain associated with duodenal ulcers is typically relieved by eating but often returns two to three hours later, and frequently awakens patients at night (DiMarino 2016a).

Helicobacter pylori infection. H. pylori infection is the primary cause of peptic ulcer disease; it is present in 30% to 50% of patients with gastric ulcers and 50% to 70% of those with duodenal ulcers (Kuipers 2015; DiMarino 2016a).

H. pylori bacteria bore into the protective mucus layer of the stomach or small intestine (duodenum) and cause an inflammatory response. Chronic inflammation induced by H. pylori damages the mucosa and disrupts pH regulation. These effects can lead to ulcer formation (UMMC 2015; Chai 2011). H. pylori infection can also increase the risk of gastric cancer (Waldum 2014).

Nonsteroidal anti-inflammatory drugs (NSAIDs). Chronic use of NSAIDs such as ibuprofen, naproxen, and aspirin is the second-leading cause of peptic ulcer disease, and the occurrence of NSAID-related ulcers is increasing, particularly in older individuals (UMMC 2015; Kuipers 2012).

By inhibiting cyclooxygenase (COX) enzymes, NSAIDs cause a decrease in the synthesis of prostaglandins that stimulate production of protective mucus and acid-buffering bicarbonate in the digestive tract. This increases vulnerability to ulcer formation. NSAIDs also increase risk of gastrointestinal bleeding (Chai 2011; UMMC 2015).

Additional Risk Factors

• Age and gender. Ulcers can develop at any age, but are most common in middle-aged adults. Men are twice as likely as women to develop ulcers (UMMC 2015).
• Smoking. Cigarette smoking increases the risk of ulcers, increases the rate of recurrence, and delays ulcer healing (DiMarino 2016a).
• Alcohol abuse. Alcohol use promotes secretion of stomach acid and damages the gastric mucosa; heavy drinkers are at increased ulcer risk. Light-to-moderate drinking has not been definitively linked to ulcers (Lee 2013; DiMarino 2016a).
• Family history. Risk of ulcers is higher in those with a relative who has a history of peptic ulcers (Lee 2013).
• Previous history of ulcers. About 80% of individuals with bleeding ulcers have had symptomatic ulcers in the past (Kuipers 2012).
• Stress. Stress is correlated with peptic ulcer disease and may compound the effects of H. pylori infection (Overmier 2013; Herszenyi 2015).
• Medication combinations. The combination of NSAIDs with corticosteroids, bisphosphonates, and certain other medications is associated with an increased risk of peptic ulcers (Lee 2013).

Common Symptoms

Up to 40% of all patients with uncomplicated peptic ulcer disease do not have symptoms. Older people in particular are likely to be symptom free (DiMarino 2016a; Kuipers 2012).

Pain is the most common symptom of peptic ulcer disease, and is often felt in the upper abdomen. It is often described as gnawing, burning, or tenderness that may be relieved by food or antacids (Lee 2013; DiMarino 2016a). Because ulcer pain may radiate to the back, chest, and other parts of abdomen, it is sometimes mistaken for other problems, including a heart attack (Ferri 2016; UMMC 2012). Pain that disrupts nighttime sleep often indicates a duodenal ulcer (DiMarino 2016a).

Other possible symptoms include nausea, vomiting, and heartburn. Severe abdominal pain, loss of appetite, weight loss, black or bloody stools, and vomiting that may include blood could indicate an ulcer complicated by bleeding or perforation; anyone experiencing these symptoms should seek medical care immediately (Kuipers 2012).

Complications

Bleeding internally is the most common complication, occurring in up to 15% of patients with peptic ulcer disease. Ulcers caused by NSAIDs are more likely to bleed than those caused by H. pylori (UMMC 2012; Milosavljevic 2011).

Perforation, in which ulcers breach the wall of the duodenum or stomach, causing damage to nearby tissues and organs, occurs more commonly in older patients and is a medical emergency requiring surgical intervention. Perforation occurs in 2% to 10% of peptic ulcers. When perforation directly affects an organ it is called penetration (Ramakrishnan 2007; Meyer 2015).

Obstruction that blocks stomach emptying can result from inflammation, spasm, or scarring from recurrent ulcers. Symptoms of obstruction include repeated vomiting as well as sustained fullness and bloating after eating (Ramakrishnan 2007; Meyer 2015).

H. pylori-associated peptic ulcer disease increases by three- to six-fold the risk of developing stomach cancer later in life (DiMarino 2016a).

The diagnosis of peptic ulcer disease is usually considered based on patient history, symptoms, and is confirmed by endoscopy. Conditions that may cause similar symptoms include effects of medications; gallbladder disease; gastrointestinal cancers; and occasionally, chronic pancreatitis. However, over half of patients with ulcers present without any symptoms. A history of use of NSAIDs or H. pylori infection should increase suspicion of peptic ulcer disease (Vakil 2023a; Vakil 2022).

Upper gastrointestinal endoscopy is the most accurate diagnostic test for peptic ulcer. Endoscopy allows inspection and biopsy of the stomach and duodenal lining as well as direct testing for H. pylori (Vakil 2023a; Vakil 2022; Vakil 2023b). Biopsy is necessary to distinguish peptic ulcer from ulcerative malignancy. Endoscopy within 24 hours is recommended for patients with signs of gastrointestinal bleeding (Wilkins 2020; Lau 2020).

All patients with suspected peptic ulcer disease should be tested for H. pylori. Urea breath testing and stool antigen test are the most reliable tests, while blood antibody testing is not considered reliable. For 1–2 weeks before testing, proton pump inhibitor (PPI) treatment should be suspended to decrease the chance of false-negative results. Four weeks or more after antibiotic treatment, eradication should be confirmed with repeat testing. In cases in which positive tests for H. pylori persist after two courses of antibiotics, endoscopy with biopsy and culture for antibiotic sensitivity should be performed (Lamont 2023).

The presence or absence of H. pylori infection is the critical determinant of ulcer treatment. Beyond eradication of H. pylori, symptom relief and promotion of ulcer healing are the main treatment objectives for uncomplicated peptic ulcers. Complications such as uncontrolled or recurrent bleeding, perforation, and obstruction may require surgery (Lee 2013; Ramakrishnan 2007; DiMarino 2016a).

H. pylori-Positive

The 2017 clinical guideline from the American College of Gastroenterology for the treatment of H. pylori recommends as first-line treatment either a combination of three antibiotics and a proton pump inhibitor (PPI) medication or “bismuth quadruple therapy” which uses a bismuth preparation, two antibiotics, and a PPI. Multiple variations of treatment based on these or similar combinations of drugs may also be considered. All recommended treatments are of 10‒14 days duration (Chey 2017).

• Antibiotics. Eradication of H. pylori by antibiotics is the mainstay of treatment for peptic ulcers associated with H. pylori, and results in a 70‒90% cure rate (UMMC 2012; Lee 2013). Recommended first-line treatment combinations include clarithromycin (Biaxin), a nitroimidazole such as metronidazole (Flagyl), and amoxicillin; or tetracycline and a nitroimidazole (Chey 2017).

  Clarithromycin resistance plays an important role in the variable estimates of cure rates for H. pylori and peptic ulcer. This is a growing problem in the United States and Canada. Resistance to metronidazole and levofloxacin (Levaquin) has also been documented (Chey 2017).

• Proton pump inhibitors (PPIs). PPIs are drugs that block the secretion of stomach acid, allowing ulcers to heal and often relieving pain (DiMarino 2016b). PPIs also enhance the efficacy of antibiotics in H. pylori eradication (Lee 2013). PPIs used for this purpose include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (AcipHex) (UMMC 2012).

  H. pylori eradication regimens are generally brief, lasting 10‒14 days. However, when used long-term, PPIs are associated with a wide range of serious side effects including kidney and cardiovascular disease (see “Potential Risks of Long-term Proton Pump Inhibitor (PPI) Use”).

• Bismuth. Bismuth-containing medications (eg, Pepto-Bismol, Kaopectate) reduce gastrointestinal acidity and improve the efficacy of standard antimicrobial therapy against H. pylori. Bismuth rarely causes systemic side effects, but can result in black and tarry stools (UMMC 2012; Lee 2013).

Salvage therapy is sometimes used when initial therapy fails; this strategy uses different antibiotics than those that previously failed. Bismuth quadruple therapy or regimens containing levofloxacin are preferred salvage regimens (Chey 2017).

In addition to antibiotic resistance, poor compliance is an obstacle to effective treatment. Triple and quadruple therapies are complicated, expensive, and cause side effects (mostly digestive) in about 30% of patients (UMMC 2015; Safavi 2016).

In most patients, drug therapy relieves ulcer symptoms, but in some cases, symptoms persist despite effective clearing of H. pylori. Long-term management of dyspepsia with acid-suppression or other treatments may be helpful in these cases (Lee 2013).

H. pylori- Negative

For patients with peptic ulcers who test negative for H. pylori, NSAID use should be discontinued if possible. Antacids and medications that reduce acid secretion including PPIs are used in these situations (Lee 2013; Ferri 2016):

Antacids. Antacids neutralize stomach acid. Antacids containing bismuth subsalicylate (eg, Pepto-Bismol, Kaopectate), calcium carbonate (eg, Tums), and a combination of aluminum hydroxide and magnesium hydroxide (Maalox, Mylanta) are available over the counter. These drugs usually cause only mild side effects, including diarrhea or constipation (IFFGD 2015; NCBI 2007).

H2 receptor antagonists. H2 receptor antagonists block the acid-stimulating action of histamine in the stomach. Examples include cimetidine (Tagamet), famotidine (Pepcid AC), and ranitidine (Zantac). They are available over the counter, but a prescription is required for higher doses. Serious side effects caused by H2 receptor antagonists are rare but more common in older patients (DiMarino 2016b; UMMC 2012; NLM 2017b). H2 receptor antagonists can reduce vitamin B₁₂ absorption, so B₁₂ status should be monitored in long-term users, and B₁₂ supplementation should be initiated if a B₁₂ deficiency is detected (Force 1992).

Mucosal protective agents. Misoprostol (Cytotec) and sucralfate (Carafate) are used to help protect the stomach lining against the damaging effects of NSAIDs in patients who must continue to take them. Misoprostol stimulates prostaglandin production, and can prevent NSAID-related ulcer, but does not heal existing ulcers. Misoprostol also inhibits stomach acid and pepsin production (CIHR 2017). Misoprostol causes diarrhea and other gastrointestinal side effects relatively frequently, and is contraindicated in pregnant women because it can cause miscarriages and birth defects (Lee 2013; Ferri 2016; UMMC 2012). Sucralfate forms a chemical barrier at ulcerated sites to protect against further damage. Sucralfate occasionally causes constipation but has few side effects, though it does interfere with a number of different medications (Gold Standard 2013; UMMC 2012).

Maintenance Therapy

Maintenance therapy is recommended for patients who experience recurrent ulcers. Maintenance therapy generally involves long-term use of antacids, H2 receptor antagonists, mucosal protectants, or PPIs. Although PPIs are usually considered the most effective maintenance treatment (Ferri 2016), long-term PPI use is associated with an array of grave health consequences and an increased risk of death (Maggio, Corsonello 2013; Shih 2014; Klepser 2013).

Silver Nanoparticles

Silver compounds have antibacterial activity through multiple mechanisms, which lowers the likelihood of microbial resistance. Silver nanoparticles gained attention in recent years as a potential tool in the battle against antibiotic-resistant organisms (Dakal 2016). Utilizing silver compounds to target H. pylori represents one such opportunity.

Laboratory and animal studies indicate silver nanoparticles have anti-H. pylori activity (Amin 2012; Kuo 2014). In one animal model, silver nanoparticles were shown to safely decrease H. pylori densities, with higher silver concentrations having stronger inhibitory effects (Kuo 2014).

Silver nanoparticles could potentially be used to lower H. pylori load, increasing the success of anti-H. pylori therapies. Human studies with longer observation periods are needed before clinical use becomes practical (Kuo 2014).

Note: silver nanoparticles should not be confused with over-the-counter colloidal silver preparations. Silver nanoparticle preparations are used in experimental settings under controlled conditions and have different physicochemical properties than readily available colloidal silver preparations. Colloidal silver preparations have not been demonstrated in published, peer-reviewed studies to have anti-H. pylori activity. In addition, colloidal silver has not been proven effective for treating any condition, and may have several side effects, including argyria—a disorder in which the skin takes on a permanent bluish-gray discoloration (Griffith 2015; NIH 2017).

Liposomal Linolenic Acid

Linolenic acid is a naturally occurring fatty acid found in vegetable oils that has antimicrobial properties. However, under normal conditions in the body, linolenic acid is not soluble and has little antibacterial activity. Liposomal technology overcomes this barrier by incorporating linolenic acid into a complex of cholesterol and phospholipids. This creates microscopic particles called liposomes that fuse with H. pylori cell membranes and efficiently deliver linolenic acid (Thamphiwatana 2014; Jung 2015).

Liposomal linolenic acid has been shown to kill H. pylori and markedly reduce its population in the stomach of mice. In addition, liposomal linolenic acid was shown to decrease levels of pro-inflammatory cytokines triggered by H. pylori (Thamphiwatana 2014).

In mice, liposomal linolenic acid was found to penetrate the gastric mucus layer where H. pylori resides (Allen 1997). A considerable amount of liposomal linolenic acid remained in the stomach lining up to 24 hours later, and no toxic effects of this treatment were observed (Thamphiwatana 2014).

Intermittent Oral Proton-Pump Inhibitor Therapy for Bleeding Ulcers

Acid suppression with PPIs reduces bleeding, although the exact mechanism behind this effect is not well understood. For patients with high-risk bleeding ulcers, current guidelines recommend a single intravenous dose of a PPI followed by continuous PPI infusion for 72 hours after endoscopic treatment. However, according to a review of studies, intermittent treatment with both oral and intravenous PPIs are as effective as continuous infusion of PPIs in patients with high-risk bleeding ulcers. Intermittent PPI therapy (oral or intravenous) has the advantages of easy administration, lower cost, and lower PPI dose than continuous infusion PPI therapy (Sachar 2014). Also, intermittent PPI therapy has been shown to reduce the total amount of PPI used, which may reduce long-term side effects, although this has not been firmly established (Laine 2016).

Diet

A diet rich in fruits and vegetables and fiber may reduce the risk of ulcers by 50%, and also help heal existing ulcers (Ryan-Harshman 2004; UMMC 2012).

Polyphenols, naturally occurring compounds present throughout the plant kingdom, are obtained from the diet, mostly from fruits, vegetables, spices, grains, coffee, tea, and wine (Cardona 2013). Polyphenols have considerable anti-ulcer potential. Preclinical, animal, and clinical studies have shown that polyphenols may influence ulcer formation and healing through modulation of inflammation, ulcer-healing qualities, and anti-H. pylori activity (Farzaei 2015).

Among the polyphenols that have demonstrated gastro-protective activity in preclinical studies are quercetin (found in onions, apples, and many other plant foods); curcumin (found in turmeric); epigallocatechin gallate (EGCG) and catechins (found especially in green and black tea); and anthocyanins (found especially in red grapes, grape juice, red wine, cranberries, and other red and purple produce) (Farzaei 2015; Mota 2009).

Polyphenols protect against ulcers by mechanisms including protection against free radical damage; fortifying mucosal defense by stimulating production of mucus, growth factors, and prostaglandins; diminishing stomach acid secretion; increasing mucosal blood flow; and exerting antibacterial activity against H. pylori (Farzaei 2015; Mota 2009).

Two clinical trials have found an anti-H. pylori effect of virgin olive oil (Castro 2012). In a preclinical study, polyphenols from virgin olive oil showed antibacterial activity against eight different strains of H. pylori (Romero 2007).

Extracts of the spices garlic, ginger, and turmeric have exhibited anti-ulcer activity in animal models of peptic ulcer, an effect that may result from protection of the mucosa against oxidative injury and inflammation (Choi 2014; Zaghlool 2015; Liju 2015). Ginger extract and curcumin have demonstrated anti-H. pylori activity in preclinical studies (Mahady 2003; Mahady 2002).

Smoking Cessation

Smokers are at twice the risk of ulcers as non-smokers. Cigarette smoking increases the chances of developing H. pylori infection, delays healing of ulcers, and makes ulcer recurrence more likely (NIH 2013; Lee 2013). Smoking cessation provides immediate benefit for ulcer healing (Parasher 2000; Eastwood 1988).

Alcohol Reduction

Alcohol can cause direct physical injury to the stomach lining and increase gastric acid secretion, and, when consumed excessively, can promote ulcer development. Alcohol consumption increases the risk of bleeding in patients with peptic ulcer disease (Lee 2013; Chai 2011; Kuipers 2012). Alcohol consumption should be avoided by people who have ulcers and those at high risk for developing ulcers.

Stress Management

Psychological stress and tension is correlated with gastric and duodenal ulcers (Cheng 2000). In a study in 47 patients with peptic ulcer disease, an integrated stress management program involving seven one-hour sessions over four weeks was compared with listening to a relaxation tape. Over four months of follow-up, those who participated in the stress management program had greater relief of stress symptoms and better ulcer healing than those who only listened to the relaxation tapes (Han 2002). A number of techniques for reducing stress are described in the Stress Management protocol.

Primary Support

Licorice and DGL. Licorice (Glycyrrhiza glabra) root has been used for centuries to treat a wide array of health problems, including peptic ulcers. Deglycyrrhizinated licorice, or DGL, is made by removing a component of licorice that has been associated with side effects such as fluid retention and high blood pressure (Shibata 2000; Borrelli 2000; UMMC 2016).

In a randomized, double-blind, placebo-controlled trial, 100 patients who tested positive for H. pylori were treated with 150 mg per day of a DGL preparation or placebo for 30 days. At the end of the treatment period, 56% of the DGL group and 4% of the placebo group tested negative for H. pylori (Puram 2013). The addition of licorice to standard treatment of H. pylori-positive ulcers has also been shown to be beneficial. In a randomized controlled trial, licorice extract improved the H. pylori eradication rate of standard triple therapy (the combination of two antibiotics plus a proton pump inhibitor [PPI]) (Hajiaghamohammadi 2016), while another controlled clinical trial found that triple therapy plus licorice extract was as effective as bismuth quadruple therapy (Momeni 2014).

Licorice root, DGL, and combinations of DGL and antacids have been studied for decades for the treatment of peptic ulcers, with many of these trials finding a positive therapeutic effect (Tewari 1968; Turpie 1969). One trial using a combination product of DGL plus antacids found this preparation to be nearly as effective as cimetidine in reducing recurrence of stomach ulcers over a two-year period (Morgan 1985). In a clinical trial, concurrent administration of DGL and aspirin significantly reduced aspirin-induced bleeding, as measured by fecal blood loss (Rees 1979).

In a rat model, the incidence of aspirin-induced ulcers was reduced by half when the aspirin was coated with different forms of licorice, including DGL (Dehpour 1994). In other animal research, a DGL preparation reduced gastric acidity and decreased ulceration due to NSAID exposure and stress (Mukherjee 2010), and both licorice root extract and omeprazole (Prilosec, a PPI) were effective in preventing NSAID-induced ulcers (Jalilzadeh-Amin 2015).

Licorice compounds present in DGL have demonstrated anti-inflammatory, free radical-scavenging, and anti-ulcer activities in preclinical research (Choi 2015; Mukherjee 2010). DGL has also been shown to increase the number of mucous-producing cells and enhance mucous secretion in the rat stomach (van Marle 1981). Animal and laboratory studies confirm that compounds in licorice and DGL have activity against H. pylori, including antibiotic-resistant strains (Kim 2013; Krausse 2004; Fukai 2002; Wittschier 2009).

Zinc-carnosine. Zinc-carnosine, also called polaprezinc, is a combination of the mineral zinc and L-carnosine, a compound composed of the amino acids beta-alanine and L-histidine. Zinc-carnosine is thought to help protect the gastrointestinal lining (Watari 2013; Mahmood 2007).

In a randomized clinical trial in 66 participants with symptomatic H. pylori infection, zinc-carnosine significantly improved the ability of standard triple therapy (two antibiotics plus a proton pump inhibitor) to eradicate H. pylori. In those who completed treatment, 86% treated with triple therapy alone achieved eradication while 100% treated with triple therapy plus zinc-carnosine (150 mg twice daily) were H. pylori-negative four weeks after treatment (Kashimura 1999). In 20 patients with injury to the small intestine caused by low-dose aspirin, treatment with 150 mg per day of zinc-carnosine for four weeks resulted in a significant reduction in mucosal injury and ulcers compared with no treatment (Watari 2013). In another trial, 10 healthy individuals were treated for seven days with 37.5 mg twice per day of zinc-carnosine, or placebo. During the final five days, study subjects also consumed the NSAID indomethacin (Indocin, Tivorbex). Those who received placebo experienced a three-fold increase in intestinal permeability (a sign of mucosal damage), while those treated with zinc-carnosine did not have a significant increase in gut permeability (Mahmood 2007).

Studies using animal models of gastrointestinal mucosal damage have also demonstrated the cell-protective and anti-ulcer effects of zinc-carnosine (Choi 2013; Cho 1991; Seiki 1990). Among zinc-carnosine’s possible mechanisms of action are a reduction in inflammation, neutralizing tissue-damaging free radicals, preventing intestinal cell death, and protecting the tight junctions that link mucosal cells together (Watari 2013; Choi 2013).

Probiotics. Probiotics are microorganisms that confer health benefits when ingested (Lesbros-Pantoflickova 2007). Lactobacillus species, commonly used in probiotics, have been shown in laboratory studies to inhibit the growth of H. pylori and reduce H. pylori-associated inflammation (Enany 2015), and numerous randomized controlled trials have found that the addition of probiotics to standard antibiotic therapy markedly improves the success of H. pylori eradication (Boltin 2016; Dang 2014; Ma 2015). In one randomized trial, probiotics combined with triple therapy (two antibiotics plus a PPI) was compared with triple therapy alone in patients with H. pylori-associated peptic ulcers. The addition of probiotics resulted in an H. pylori eradication rate over 24% higher, and a total treatment effectiveness rate over 13% higher, compared with triple therapy alone (Ma 2015).

An important potential benefit of probiotics is the reduction of antibiotic-associated side effects, particularly diarrhea (Boltin 2016). An analysis of randomized controlled trials determined that Saccharomyces boulardii, a probiotic yeast, decreased side effects of antibiotic treatment of H. pylori (Dang 2014).

Lactobacillus reuteri DSM17648 is a probiotic strain that specifically binds to H. pylori bacteria in the gut, preventing them from adhering to the gastric mucosa and reducing their numbers in the stomach. L. reuteri DSM17648 supplements have been shown to decrease the H. pylori load in healthy H. pylori-positive individuals, and may thus prevent future H. pylori-associated problems, including the need for antibiotic treatment. These clinical effects of L. reuteri DSM 17648 were also demonstrated by preparations in which the L. reuteri bacteria were killed by freeze-drying or spray-drying procedures (Holz 2015; Mehling 2013). Similarly, S. boulardii has been found to reduce gastric colonies of H. pylori in symptom-free H. pylori-positive subjects (Namkin 2016).

Lactoferrin. Lactoferrin is a component of milk (Vogel 2012). It has been the subject of numerous clinical trials investigating its ability to eradicate H. pylori. A meta-analysis examined five randomized controlled trials that evaluated whether lactoferrin treatment was effective for H. pylori eradication. A total of 682 subjects took part in these trials, 316 of whom received lactoferrin, with the remainder serving as controls. Those who received lactoferrin had more than 2.2-fold higher odds of eradication compared with controls (Sachdeva 2009).

A later review suggested a number of different mechanisms by which lactoferrin could have an anti-H. pylori effect, including a complementary action to antibiotics, inhibition of H. pylori growth, and a reduction in the rate of treatment side effects (Sachdeva 2014).

Flavonoids/polyphenols. Polyphenols, naturally occurring compounds present throughout the plant kingdom, are obtained in the diet mostly from fruits, vegetables, spices, grains, coffee, tea, and wine (Cardona 2013). Flavonoids make up the largest group of polyphenolic compounds. Evidence from numerous studies indicate polyphenols, including flavonoids, hold promise in the prevention and treatment of peptic ulcers (Farzaei 2015; Mota 2009). Extracts from tea, apples, pomegranate, and grape seed are especially good sources of polyphenols with possible anti-ulcer and anti-H. pylori activity (Farzaei 2015; Ankolekar 2011).

Curcumin, the principal active ingredient in the spice turmeric (Curcuma longa), is a flavonoid with strong free radical-scavenging, anti-inflammatory, and anti-bacterial properties. In particular, curcumin has been found to reduce symptoms in those with H. pylori-associated ulcers when used in combination with standard triple therapy (two antibiotics plus a PPI) (Khonche 2016; Di Mario 2007). Preclinical and animal studies have found that curcumin protects against NSAID-induced and stress-induced ulcers by increasing gastric blood flow, decreasing gastric acid secretion, protecting against mucosal injury, and reducing H. pylori-induced inflammatory tissue damage (Sharma 2012; Morsy 2013; Kim 2016; Santos 2015).

Quercetin is a flavonoid found in a wide variety of plants and plant foods (Suganthy 2016). Findings from animal studies suggest quercetin may help prevent and heal peptic ulcers (Suzuki 1998; Yan 2011; Zahorodnyi 2003). Quercetin’s antihistamine activity may reduce gastric acidity (Farzaei 2015; Kahraman 2003).

Additional Support

Cranberry. Cranberry (Vaccinium macrocarpon), a good source of anthocyanins and well known for its usefulness against urinary tract infections, has also demonstrated anti-H. pylori properties in preclinical, animal, and clinical models (NIH 2016; Matsushima 2008).

In a randomized controlled trial in a population at high risk for stomach cancer, 90 days of twice-daily consumption of cranberry juice was more effective than placebo at suppressing H. pylori infection (Zhang 2005). In another randomized controlled trial, the addition of cranberry juice to triple therapy (two antibiotics plus a PPI) markedly improved the rate of H. pylori eradication in women (Shmuely 2007).

In preclinical research, cranberry extract inhibited the growth and proliferation of H. pylori. This action was attributed to its polyphenol components (Matsushima 2008). A compound from cranberry has been shown to prevent H. pylori from attaching to stomach lining cells and to mucus (Burger 2002; Burger 2000).

Glutamine. Glutamine, the most abundant amino acid in the body, is a major metabolic fuel for cells of the intestinal lining and immune cells (Zuhl 2015; Lacey 1990). Preclinical, animal, and human studies have shown that glutamine supplementation can help repair the intestinal lining (Zuhl 2015; Wang 2016).

Glutamine supplementation may be beneficial in preventing injury due to H. pylori infection. In a study in mice infected with H. pylori, supplemental dietary glutamine protected the stomach mucosa by modulating the immune response to H. pylori and reducing inflammation (Hagen 2009). In another study, long-term supplementation with glutamine prevented cancerous change in gastric mucosa of H. pylori-infected gerbils (Amagase 2010).

Vitamin C. In multiple trials, vitamin C deficiency has been associated with peptic ulcer disease, gastritis, H. pylori infection, and bleeding from peptic ulcers (Aditi 2012). At least one author has proposed that vitamin C may help prevent reinfection in those who have been treated for H. pylori infection, based on experimental evidence that vitamin C inhibits growth and colonization of H. pylori (Pal 2011).

In a randomized controlled trial, the addition of oral vitamin C (500 mg per day) to bismuth quadruple therapy was compared with the same quadruple therapy alone. The addition of vitamin C resulted in a significantly higher H. pylori eradication rate (78% vs. 49%) (Zojaji 2009). In a randomized clinical trial in patients with H. pylori infection and chronic gastritis, high-dose vitamin C treatment (5 grams daily for four weeks) resulted in H. pylori eradication in 30% of patients (Jarosz 1998).

Magnesium. Magnesium salts are common ingredients in antacid formulations, but magnesium also appears to possess important anti-ulcer properties. In one animal study, rats were pre-treated with magnesium before administration of an NSAID (indomethacin) to induce ulcers. Compared with an untreated control group, the magnesium-treated rats had significantly reduced ulcer formation. The anti-ulcer effects of magnesium were attributed to its ability to decrease the number of acid-secreting cells and increase the number of mucous-producing cells in the stomach (Adewoye 2013).

Whey protein. In animal studies, whey and whey protein-derived compounds have demonstrated ulcer-protective properties (Castro 2010; Rosaneli 2004; Rosaneli 2002). These effects of whey protein may be related to its role in raising levels of glutathione, which shields the mucosal lining from free radical damage (Rosaneli 2002). Whey protein contains high levels of sulfur-containing amino acids such as cysteine, which is utilized in the synthesis of glutathione, a powerful scavenger of free radicals (Zavorsky 2007). Increased mucous production and lower plasma gastrin (an acid-stimulating hormone) may also help explain whey protein’s mucosal protection (Castro 2010).

Phospholipids. The prevalence of duodenal ulcers is higher in countries where the diet is based on refined plant foods such as milled rice and wheat. Conversely, the duodenal ulcer rate is lower in countries where staple foods consist of unrefined wheat, corn, soy, millet, and legumes. Experimental studies have determined that the lipid portion of these whole, unrefined foods (eg, oil from wheat germ or bran) protects the stomach and duodenal mucosa by increasing gastric mucous production and forming a protective barrier against stomach acid (Tovey 2015). Within the lipid portion, phospholipids have been identified as active components (Tovey 2015; Tovey 2013).

In a clinical trial, 204 subjects between 50 and 74 years old were given either aspirin (325 mg daily) or the same dose of aspirin complexed with phosphatidylcholine for seven days; those who received the phosphatidylcholine-aspirin complex had less evidence of gastric and duodenal mucosal damage and ulcers compared with those receiving aspirin alone (Cryer 2011). Animal studies suggest phospholipids may protect against the damaging effects of other NSAIDs such as naproxen and indomethacin as well (Tovey 2015).

Aloe vera extract. Aloe vera extracts have been shown to have healing and anti-inflammatory effects for skin damage, burns, pain, and edema. Preclinical and animal studies have found that Aloe vera also has gastroprotective and anti-ulcer properties (Keshavarzi 2014; Eamlamnam 2006).

In an early trial in 12 patients diagnosed with peptic ulcer disease, administration of a tablespoon of Aloe vera gel emulsion daily led to complete recovery (Blitz 1963). Results from animal studies indicate Aloe vera inhibits secretion of stomach acid (Keshavarzi 2014; Yusuf 2004), reduces gastric mucosal inflammation, and enhances stomach ulcer healing (Eamlamnam 2006; Park 2011). In a laboratory study, the inner gel of Aloe vera inhibited the growth of H. pylori bacteria, including antibiotic resistant strains (Cellini 2014).