Abstract

Purpose of review: The management of Peptic Ulcer Disease (PUD) is achieved using pharmacological agents to counteract the aggressive factors or stimulate the mucosal defence. In recent years, plant-based bioactive products have gained popularity as an alternative management protocol due to the increased antibiotic resistance of Helicobacter pylori (H. pylori), lower cost, perceived effectiveness, availability, and little side effects. In this review, we summarized the conventional treatment methods, alternative bioactive compounds, and the dietotherapy of PUD.

Recent findings: The conventional management methods include antacids, gastric muscle stimulants, mucosal-increasing resistance agents, antisecretory medications (anticholinergic agents), and Proton Pump Inhibitors (PPIs). Most of the plant’s bioactive compounds are alkaloids, terpenes, flavones, isoflavones, flavonols, chalcones, flavanones, xanthones, flavan-3-ols, anthocyanins, and capsaicinoids. These bioactive compounds work in a dose-dependent manner and express their therapeutic functions through pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1 beta (IL-1β), and Interleukin-6 (IL-6), resulting in a reduction in prostaglandin E2. No food product has a history of causing the PUD, but some foods are prohibited or need to be taken with caution. Some of these food items, such as spicy foods, caffeine, and alcohol, can hinder healing and worsen the symptoms while fibres, vitamins C and A, zinc, iron, and selenium can promote healing.

Conclusion: While there are limited articles in the literature to elucidate the dietotherapy of PUD, a balanced diet should always be provided in this course to manage the pathology. The paucity of this information opens up more research opportunities in PUD dietotherapy.

Keywords: Helicobacter Pylori; Gastric defence factors; Aggressive factors; Antibiotic resistance; Pro-inflammatory cytokines; Balanced diet.

Citation: Anchang MM, Okoyeuzu FC, Okafor JN, and Okafor GI. The management of peptic ulcer disease using conventional methods, bioactive compounds and dietotherapy: A review. J Gastroenterol Res Pract. 2024; 4(5): 1202.

Introduction

Peptic ulcer is a sore in the gastrointestinal lining resulting in the breakdown of the mucosal and submucosal layers [1]. Peptic ulcers come about due to the peptic acid injury of the gut, leading to the breakdown of the digestive system’s mucosal layer, with injury greater than 3-5 mm [1]. This injury can occur along the oesophagus (oesophageal ulcer), stomach walls (gastric ulcer), and the duodenum (duodenal ulcer). It occurs due to rupturing of the mucosal layer’s protective barrier for these three digestive system components. Individual susceptibility to Non-Steroidal Anti-inflammatory Drugs (NSAID) toxicity and H. pylori virulence determines the degree of damage to the mucosa layer. The mucosa layer has the unique ability to resist injury resulting from high peptic acid concentration, influx of bile, and pepsin [2]. The breakdown of this layer is due to the imbalance between the protective and aggressive factors of the mucosal layer [3].

The protective factors include bicarbonate (HCO3 - ), the mucus barrier consist of 95% water and 0.2-5.0% mucins, ions, lipids, cell debris, DNA, and salts, the endogenous antioxidant system’s synthesis of cytoprotective Prostaglandins (PGs), Nitric Oxide (NO), and adequate blood flow [2,3]. Other protective factors include the hydrophobic mucosal surface epithelium, which can repel acids and other water-soluble agents. Aggressive factors that compromise the integrity of the mucosal layer include Helicobacter pylori, which is the leading causative agent [4], and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), which are the second-most causative agents [1]. H. pylori accounts for about 70% of the cases, while NSAIDs account for about 10% [5]. Other aggressive factors include Hydrochloric Acid (HCl), pepsin activity, bile reflux, and decreased blood flow. Also, some exogenous actors include inappropriate eating habits, stress [6], and chemical agents such as alcohol, smoking, hygienic conditions, level of education, low socioeconomic status, poor water supplies, and financial status [7,8]. The etiopathogenesis of peptic ulcer disease is presented in Figure 1.

The mode of invasion by H. pylori starts when the bacterium creates an environment required for its survival in the stomach beneath the mucosal barrier by producing urease. Additionally, the bacterium expresses adhesins like the blood group antigen adhesin (BabA) and the Outer inflammatory protein Adhesin (OipA) that aid the bacterium in adhering to the gastric epithelium. The virulent factors CagA and PicB, encoded by a pathogenic genome island, and other bacterial factors, interact aggressively with host tissue and be associated with gastric mucosal inflammatory cell and activate stomach epithelial injury [9]. Again, NSAID can increase complications of peptic ulcers by four folds and aspirin can increase the risk by two folds [10]. This is through the inhibitory effect of prostanoid biosynthesis caused by NSAID and aspirin. Prostanoids (prostaglandins, thromboxanes, prostacyclins) are derivatives of arachidonic acid obtained with the help of Cyclo-Oxygenase (COX) isoenzymes after cell lesions [11]. NSAID exert the inhibitory effect by limiting the action of COX 2 enzymes that are needed in the synthesis of prostanoids. Risk factors that have been associated with the acquisition and prevalence of H. pylori infection in West and Central Africa include poor sanitary practices, family income, educational level, age, occupation, some religious practices, and poor water supplies [12].

Although, its complications have remained constant, about 5-10% of the general population worldwide is infected with PUD, with about four million people infected annually [13,14]. In western countries, the prevalence is 0.1-0.3% [1]. Introducing new therapies for treating this disease in developed countries has reduced its frequency of occurrence. In sub-Saharan Africa, the prevalence is high, at 24.5% in dyspeptic patients compared to 12-25% for symptomatic patients [15]. In 2019, the prevalence amounted to 8.09 million people worldwide, with a further tendency to increase [5]. Comparing the prevalence of PUD in different parts of Africa, studies have revealed that the prevalence in Northern Savana is lower than in Central and Western parts of Africa [15]. Studies have shown that the incidences in Sub-Saharan African countries are higher in women than in men, with the mortality rate in males being higher than in females except in Central Sub-Saharan Africa [5]. In Ghana and Nigeria, the incidence in females is about 54-57% [15]. In some 264 children, aged 2-11 years who were administered in Cottage Hospital Inyi, Nigeria, 16% of those children were diagnosed with PUD, with 8.3% cases in females and 7.6% of the cases in males [16]. In the Northern part of Nigeria (Kanu State) a study conducted at a teaching hospital showed that in a sample size of 70 patients, 64.3% were males while 35.7% were females, with the highest number of cases found in patients aged between 31-50 years [17]. Generally, for patients with gastric ulcers (stomach), the symptoms are postprandial abdominal pain, vomiting, nausea, and weight loss. For patients with duodenal ulcers, the symptoms include abdominal pain at night and the feeling of being hungry [18]. Other complications include bloating, fullness, heartburn, bleeding, perforation and gastric outlet obstruction, with fatality rate between 5-10% [19].

Management of PUD

The use of conventional drugs for the management of PUD

Healing peptic ulcers and avoiding potential relapses are possible with H. pylori eradication alone, however, due to H. pylori’s growing antibiotic resistance to standard medications, this endeavour is challenging. Since PUD is caused by an imbalance in the defensive and aggressive factors, its treatment can focus on stemming the aggressive factors or strengthening the defensive mechanism. Proton Pump Inhibitors (PPI), clarithromycin, bismuth salt, tetracycline, amoxicillin, metronidazole, and other medications are frequently used to treat PUD [20]. If the use of the NSAIDs is stopped, PPIs can treat more than 85% of PUD cases caused by NSAIDs or aspirin in 6 to 8 weeks. A combination of COX-2-selective NSAIDs and PPI is the most effective defence against PUD caused by NSAIDs [21]. Antiulcer medications’ sites of action or modes of action can be used to categorize them. Examples include antacids, gastric muscle stimulants, mucosalincreasing resistance agents, antisecretory medications (anticholinergic agents), corticohypothalamic drugs, and Proton Pump Inhibitors (PPIs). Table 1 summarizes the conventional drugs used in treating PUD and the groups to which each drug belongs.

Figure 2 displays the algorithm for treatment of peptic ulcers caused by Helicobacter pylori. Proton pump inhibitors and two antibiotics, namely clarithromycin and either amoxicillin or metronidazole, are used in the treatment for 7-14 days. This therapy is called the proton pump inhibitor-based triple therapy [1,20].

The use of plant bioactive compounds

Plant-based products have gained popularity as an alternative treatment over commercially available synthetic drugs in the management of PUD due to increased antibiotic resistance of H. pylori, lower cost, perceived effectiveness, and availability, and because of little or no adverse side effects [22]. Examples of some of the major bioactive compounds with a track record of use in the management of peptic ulcer disease are presented in Table 2.

Dietotherapy of PUD

The long history of a balanced diet having the potential to treat and eradicate chronic diseases and enhance health is no longer news. To this effect, dietotherapy has played a significant role in the management of peptic ulcers, with the potential to protect the gastrointestinal lining, reduce pain, improve digestion, and improve nutritional status [23]. Dietotherapy for peptic ulcers always aims to prevent acid hypersecretion and subsequent pain reduction in the gastric and duodenal mucosa, as a decrease in this acid secretion promotes overall healing [24]. There may be no ideal diet that can express this effect on all individuals, as people have different nutritional needs. Hence, understanding the dietary deficiencies of people suffering from peptic ulcers can be crucial in formulating recovery diets. However, as a rule of thumb, functional food for the management of peptic ulcer should contain; energy (25-30 Kcal/Kg), proteins (12-15% or 1.2-1.5 g/Kg/weight), carbohydrates (50-60%), lipids (25-30 g/day), fibre (20-30 g/day), zinc (40 mg), selenium (400 µg), vitamin A (3000 µg/day), vitamin C (500 mg), vitamin B12 (2.4 µg), folic acid (400 µg), iron (45 mg), and probiotics containing 109 to 1011 cfu/day lactic acid bacteria [24].

Particularly helpful in the management of peptic ulcers is fibre. The different physicochemical properties of fibres make them have a broader effect on organisms, demonstrating different effects on the gastrointestinal tract. Fibres regulate bowel function and, thus, are crucial in maintaining health and managing many GI tract-related pathologies. The health claims are remarkably higher for soluble fibres that add bulk to the stool and reduce food transit time through the gut. According to HealthLinkBC [25], a diet high in fibres, especially soluble fibres from vegetables, fruits, beans, oatmeal, and peas, can manage peptic ulcers. The World Health Organization recommends 20 to 30 g of fibre daily to manage the disease. The fibres act as buffers, lowering bile concentration, and abdominal bloating, and reducing pain and discomfort in the gastrointestinal tract [23,24,26].

Vitamin A can increase mucus production in the gastrointestinal tract, so a diet rich in vitamin A can be beneficial in treating peptic ulcer disease [27]. A 100 mg/kg dose of carotenoid extract has shown the ability to reduce NO production, IL-6, and prostaglandin E2 in gastric ulcer rats induced with HCl and ethanol [28]. In addition to Vitamin A, Vitamins E, C, and B12, selenium, and iron have also shown prospects for managing the disease. In a study by Yousaf et al. [29] in ulcer rats experimentally induced with indomethacin, 400 mg/kg body weight of Vitamin E increased mucus production in the gastric glands compared to the groups that were not treated with Vitamin E, indicating the efficacy of Vitamin E in PUD management. In another study by Sezikli et al. [30], 500 mg/kg body weight and 200 mg/kg body weight of vitamins E and C were administered to patients with H. pylori for four weeks. At the end of the four weeks, the concentration of H. pylori, the principal cause of peptic ulcer disease, was significantly reduced. This indicated the potency of these two vitamins in managing peptic ulcer disease since it eliminated the vector responsible for the condition. On the other hand, Mwafy and Afana [31] investigated the histopathological parameters of serum iron and vitamin B12 levels in hospitalized patients suffering from H. pylori infections and regular healthy patients as a control group. Results of the study showed that patients infected with H. pylori were deficient in vitamin B12 and iron compared to the control group. After treatment of the patients with omeprazole, amoxicillin, and clarithromycin, vitamin B12 and iron levels were normalized by the triple effect treatment. Iron and vitamin B12 levels can be a helpful marker for PUD. In addition to dietotherapy and the nutrients highlighted above, zinc and selenium can help accelerate healing. While zinc is essential in maintaining the immune system functions [32], selenium, on the other hand, helps to reduce disease complications and improve the healing process [33].

While no food can cause PUD, certain food items, such as spicy foods, caffeine, and alcohol, can hinder healing and worsen the symptoms in some patients. Table 3 summarizes the recommended foods that can help accelerate healing, those to be taken cautiously and foods that are prohibited in patients as they can slow the healing process and worsen symptoms.

Table 1: The types of conventional drugs used in the treatment of PUD.

Table 2: Plant bioactive compounds in the management of peptic ulcer disease.

Table 3: Foods allowed, prohibited and those which need to be taken with caution to manage PUD.

Conclusion

It has been deduced from the review that some of the significant plant bioactive compounds that have a track record in the management of peptic ulcer disease are in the major groups of alkaloids, terpenes and terpenoids, flavones, isoflavones, flavonols, chalcones, flavanones, anthocyanidins, xanthones, flavan3-ols, anthocyanins, and capsaicinoid. Most of these bioactive compounds work in a dose-dependent manner and express their therapeutic functions through the pro-inflammatory cytokines such as the TNF-α, IL-1β, and IL-6, reduction in prostaglandin E2 in both in vivo and in vitro models. The therapeutic effect of these bioactive compounds is also expressed through the radical scavenging activity and gastroprotective activity by normalizing the SOD, increased CAT, a decrease in MPO, NO, as well as in the suppression of Malondialdehyde (MDA) and nuclear factor-κB (NF-κB).

While no food product has a history of causing the PUD, there are some food items which need to be taken with caution or are prohibited by peptic ulcer patients. Some of these foods, such as spicy foods, caffeine, and alcohol, can hinder healing and worsen the symptoms in some patients. Understanding the nutritional needs of patients with PUD is one of the first and fundamental steps in formulating the required dietotherapy for this health challenge. As a rule of thumb, a balanced diet should always be provided in this course to manage the pathology. Unfortunately, there are scanty articles in the literature to elucidate the ideal dietotherapy of PUD.

Hence, there is a need to fill the gap through more research.

Abbreviations: 5-HT: 5-Hydroxytryptamine; AKT- Protein Kinase B; Baba: Antigen Adhesin; CAT: Catalase; CINC-1: CytokineInduced Neutrophil Chemoattractant-1; COX: Cyclo-Oxygenase; EGF: Epidermal Growth Factor; Gpx: Glutathione Peroxidase; Hcl- Hydrochloric Acid; HCO3 -: Bicarbonate; HMGB1: High Mobility Group Box 1; HMOX-1: Haeme Oxygenase 1; IL-1β: Interleukin-1 Beta IL-6 : Interleukin-6; Inos: Inducible Nitric Oxide Synthase; MAPK: Mitogen-Activated Protein Kinase; MDA: Malondialdehyde; MMP-2: Metalloproteinase-2; MPO: Myeloperoxidase; NE: Noradrenaline; NF-Κb: Nuclear Factor-Κb; NFΚb: Suppressed Nuclear Factor-Κb; NO: Nitric Oxide; NSAID: Non-Steroidal Anti-Inflammatory Drugs; Oipa: Outer Inflammatory Protein Adhesin; PGE2: Prostaglandin E2; Pgs: Prostaglandins; PI3K: Phosphatidylinositol-3 Kinase; PPAR-Ɣ: Peroxisome Proliferator Activated Receptor-Ɣ; Ppis: Proton Pump Inhibitors; PUD: Peptic Ulcer Disease; SOD: Superoxide Dismutase; TLR4: Toll-Like Receptor 4; TNF-Α: Tumor Necrosis Factor-Alpha.

Declarations

Conflict of interest: The authors declare that they have no competing interests to disclose

Funding: African-German Network of Excellence in Science (AGNES), and Sigma XI, the Scientific Research Honours Society with grant number G20221001-3797

Acknowledgement: The authors thank the African-German Network of Excellence in Science (AGNES) for granting Anchang Mumukom Maximus a Mobility Grant in 2023; the Grant is generously sponsored by the German Federal Ministry of Education and Research and supported by the Alexander von Humboldt Foundation. The authors also thank the Sigma Xi, The Scientific Research Honor Society for the Grants in Aid of Research awarded to Anchang Mumukom Maximus.

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