Association between dietary antioxidant index and risk of Helicobacter pylori infection among adults: a case–control study

Helicobacter pylori (H. pylori) is a gram-negative, microaerophilic and spiral shape pathogen, which replicates in the gastric epithelium layer and can be transferred directly (oral–oral) or indirectly (fecal–oral) to another. [1]. Approximately, there were 4.4 billion individuals with H. pylori infection worldwide [2]. In a study conducted in Jordan, Iran, Russia, China, Canada and Latin American countries, a large outbreak of H. pylori infection was reported [3]. This bacterium recognized to main factor of chronic gastritis, peptic ulcer and primary gastric lymphoma and according to the definition of the International Association for Cancer Research (IARC) type I carcinogenic agent [4]. The pathogenic effect of Helicobacter pylori infection is more in the upper gastrointestinal tract. Helicobacter pylori can indirectly affect the brain-gut axis in addition to its direct proinflammatory and cytotoxic effects [5].

Along other risk factors, nutrition and nutritional status play an important role in Helicobacter pylori infection. Therefore, a balanced diet, especially high consumption of fruits and vegetables, might protects people versus he consequences of H. pylori infection [6]. In a study that assessed the association of dietary patterns with H. pylori infection, high intake of grain and vegetables, was inversely related to Helicobacter pylori infection [7]. On the contrary, a diet full of carbohydrates and sweets was related to a higher H. pylori infection prevalence [8].

Enough intake of dietary antioxidants predominantly from fruits and vegetables can provide a balanced defense mechanism against the harmful effects of reactive oxygen species [9]. Bacterial growth is inhibited by antioxidants through reducing reactive oxygen species and inflammations caused by H. pylori [10]. Studies have indicated that H. pylori infection is related to the deficiencies in vitamin A, C, and E [11‐14]. Moreover, vitamins C and E has shown an inhibitory effect on H. pylori intensity and neutrophilic activity [15, 16]. The gastric epithelium damage which is caused by H. pylori has a direct relationship with reduced concentration of vitamin C [9]. Several studies have shown that concentration of vitamins C and E are lower in peoples with H. pylori than in those without H. pylori [17‐21].

The dietary antioxidant index (DAI) has become a valid indicator that considers total dietary antioxidant properties at once. As the importance of dietary antioxidants has been shown in the prevention and control of H. pylori infection, the total dietary antioxidant capacity can be evaluated by the DAI in these patients. Based on our knowledge the present study is the first study which was planned and conducted to investigate the relation to between DAI and H. pylori infection.

Among 153 patients with H. pylori infection and 306 healthy subjects, finally, 148 case and 302 controls had completed information regarding dietary intakes and were included in the statistical analysis after excluding individuals who over-or under-estimated their energy intake. The mean age of study participants was 38.72 ± 10.61 years, and 59.8% were female. General characteristics of case and control groups are indicated in Table 1. Compared with those in the control groups, individuals with H. pylori infection were significantly older, had higher BMI and smoked more. No other significant difference was observed in. Other characteristics (Table 1).

As we show in Table 2, individuals with H. pylori had a lower intake of vitamin E, vitamin A, manganese, and selenium compared to controls. Other differences in dietary intakes among the cases and controls were not significant.

The mean of total DAI was significantly higher in controls (7.67) when compared with H. pylori cases (3.57) (P < 0.001). The crude and adjusted ORs (95% CIs) for the underlying associations between both continuous and categorical DAI with H. pylori risk have been shown in Table 3. We observed a significant decrease in the H. pylori risk (OR 0.82, 95% CI: 0.75–0.89, P < 0.001) when continuous DAI was increased. Participants with less than median DAI values had increased risk of H. pylori onset (adjusted OR 1.08, 95% CI: 1.02–1.12, P < 0.001).

In the current study, DAI as a continuous variable was inversely associated with H. pylori infection. We also found a significant positive association between lower DAI and odds of H. pylori infection in functional categories (≤ Median vs. > Median). H. pylori is one of the most common bacterial infections in human beings. The role of H. pylori infection in gastric cancers and other gastrointestinal tract diseases has been widely established [28]. Available evidence indicates that diet has important role in developing H. pylori infection. Therefore, protective dietary factors are important from a public health point of view. While some nutritional research has widely focused on single nutrients or foods in diet-disease relations, the overall diet could be more informative because humans typically consume a combination of nutrients and foods. Dietary indices such as DAI are one of the approaches for this purpose which considers the whole quality of the diet. A significant inverse association has been reported between DAI and some diseases with inflammatory nature, including gastric cancer [29], colorectal cancer [30], nonalcoholic fatty liver [31], and obesity [32]. To our knowledge, no previous studies have investigated DAI in relation to H. pylori infection. The results from this study are consistent with a cross-sectional study, which found healthy subjects significantly have higher intakes of fruits, vegetables, and vitamin C compared to subjects with H. pylori infection. However, no significant differences were observed in vitamin A and E and zinc intake [33]. In another study that examined the association of dietary factors with H pylori re-infection, high consumption of fruit and vegetables, which contains vitamin C, was associated with decreased risk of H pylori re-infection [34]. In a cross-sectional study on 1106 men and women, plasma vitamin C level for H. pylori-infected patients was only 80% of that for non-infected individuals [18]. Similar findings were also seen in the study of Annibal et al., in which plasma ascorbic acid concentrations were lower in H. pylori -infected groups than in healthy controls [35]. Finding from a small randomized clinical trial showed that Zinc L-carnosine supplements in combination with three medications (lansoprazole, amoxicillin, clarithromycin) could significantly improve the cure rate for H. pylori [36]. It has been shown that H. pylori-infected patients with non-atrophic chronic gastritis had lower zinc concentrations in gastric mucosa than uninfected patients with the same type of gastritis [37]. Our findings were also consistent in line with evidence from animal studies. For example, one study reported that high doses of vitamin C could inhibit the in vitro and in vivo colonization of H. pylori [38]. In an animal study, a high intake of selenium, β-Carotene, and vitamins A, C, and E in the Guinea Pig led to a significant reduction in H. pylori growth [39]. Two further animal studies reported that zinc supplementation inhibits H. pylori -induced gastric mucosal oxidative inflammation in gerbils [40, 41]. In contrast to our findings, two meta-analyses of randomized controlled trials reported that supplementation with vitamins C and/or E could not improve the eradication rate of H. pylori [42, 43]. The reason that high doses of vitamin C is not able to eradicate H. pylori infection might be explained by the fact that at chronic infection, some patients develop relative achlorhydria that leads to lower acidity of gastric juice [44]. In such conditions, the anti-urease role of vitamin C in eradicating H. pylori is relatively less important. Furthermore, the complex mixture of diet-deriving nutrients may be more effective than high doses of single micronutrient supplements. It is possible that such nutrients interact or work together but have smaller effects individually [45]. Moreover, this non-significant effect may be partly due to the small sample size, limited duration of intervention, and low to moderate methodological quality of some of the H. pylori RCTs. Therefore caution is needed in interpreting the results of such studies.

Several biologically plausible reasons may explain why dietary antioxidants might be, either directly or indirectly, a protective factor againstH.pylori infection. It is well-known that antioxidants, with their free radical scavenging activities, can inhibit the growth of H. pylori [39]. H. pylori is urease positive and can synthesize a large amount of urease for ammonia production to neutralize the gastric acid, allowing it to colonize in the stomach epithelium [46]. It has been shown that vitamin C inhibits urease activity [47]. Moreover, vitamin C improves the stimulation and activity of granulocytes, macrophages, lymphocytes, and immunoglobulin production [34, 48]. In vitro studies, showed that zinc inhibits the urease enzyme and prevents H.pylori adhesion to gastric mucin. Mucosal inflammation may be required for H. pylori infection to persist, and the anti-inflammatory effects of antioxidants could inhibit H. pylori growth [39, 49].

This study included both strengths and weaknesses that should be noted. Our study is the first report to investigate the association of DAI and H. pylori infection; it has high scientific competence and novelty level. Moreover, results were significant in different statistical approaches (continuous and categorical). We also used valid and reliable questionnaires for data collection, which can further support the accuracy of findings. The nearly complete participation of identified cases and controls is another strength of our study. Limitations of the current study are generic concerns for case–control studies. The causality of the associations cannot be established from this study. Because we used FFQ for dietary assessment, inaccurate measures of dietary intakes may have resulted in misclassification. As participants reported past dietary habits, recall bias may have occurred, particularly among patients, as changes in lifestyle may occur when H. pylori infection develops and becomes symptomatic. Nevertheless, we included newly diagnosed patients who were interviewed by uniformly trained interviewers in their hospital settings and were unaware of any study hypothesis to minimize changes in dietary habits. It is possible that selection bias may have resulted from using hospital-based controls since these controls include individuals with conditions that could potentially be related to their dietary antioxidants intake. Moreover, the significant association between DAI and H. pylori infection could be due to unmeasured or residual confounding. Finally, we did not have data on cooking methods of antioxidant-rich foods that could alter the antioxidant content of such foods.