The role of the Mediterranean diet in the management of inflammatory bowel disease: a narrative review

Article information

Intest Res. 2025;.ir.2025.00043

Publication date (electronic) : 2025 November 19

doi : https://doi.org/10.5217/ir.2025.00043

Peter Vivian Acire

, Stephanie C. Brown

, Andrew S. Day

Department of Paediatrics and Child Health, University of Otago Christchurch, Christchurch, New Zealand

Correspondence to Andrew Day, Department of Paediatrics and Child Health, University of Otago Christchurch, Riccarton Avenue, Christchurch 8041, New Zealand. E-mail: andrew.day@otago.ac.nz

Received 2025 May 6; Revised 2025 July 30; Accepted 2025 August 12.

Abstract

Inflammatory bowel disease (IBD) is characterized by the presence of gastrointestinal inflammation, that in some individuals leads on to complications, including strictures. IBD can be associated with significant morbidity with disruption of daily activities. Although the precise cause of IBD is unknown, epidemiologic studies indicate that diet is one contributory factor. Furthermore, various specific nutritional interventions have roles in the management of IBD. While the contribution of the Mediterranean diet (MedDiet) to the development or management of IBD has not yet been clearly delineated, available data are generally supportive. The MedDiet includes the consumption of a pattern of particular foods, such as plentiful vegetables, fruit, seafood, and olive oil, along with lifestyle features. Adherence to a MedDiet is associated with enrichment of beneficial components of the intestinal microbiome and enhanced barrier function: outcomes that are likely beneficial to individuals with IBD. The focus of this review was to highlight the evidence for the MedDiet in the setting of IBD, whilst giving an overview of the underlying health impacts of the MedDiet and the putative mechanisms of this dietary approach.

Keywords: Mediterranean diet; Inflammatory bowel diseases; Induction; Remission

INTRODUCTION

The condition known as inflammatory bowel disease (IBD), is characterized as an incurable, debilitating, and chronic inflammatory disorder of the gastrointestinal (GI) tract [1]. While the 2 main types of IBD, Crohn’s disease (CD) and ulcerative colitis (UC), share many overlapping clinical, epidemiological, and inflammatory features, other findings are utilized to differentiate one from the other. CD can be characterized by the involvement of any (and sometimes all) segments of the GI tract, with transmural inflammation that may include the presence of mucosal granulomata. UC, however, typically involves inflammatory changes restricted to the colon, with varying extent of involvement from the rectum proximally [2].

Although the exact pathogenesis of IBD has not been ascertained, it is best considered that IBD develops following interactions between the host immune system and the intestinal microbiome, triggered by various environmental factors in a person with 1 or more underlying genetic risk factor [3,4]. Diet appears to be one of the key environmental factors [5]. Dietary patterns contribute to the homeostasis of the gut microenvironment, with influences upon the composition and function of the intestinal microbiome, and also upon the gut barrier, host immunity, and other components of normal gut physiology [6,7]. Diet and nutritional components may be relevant not only to the development of IBD but also to the course of the disease after diagnosis [8].

Several specific nutritional interventions have been shown to have roles in the induction of remission of IBD. Some nutritional interventions also have longer-term roles in the maintenance of remission and prevention of disease complications. For example, exclusive enteral nutrition (EEN), comprising the use of a completely liquid diet and exclusion of ordinary foods for a number of weeks, leads to high rates of remission in individuals with active CD along with nutritional improvements and mucosal healing [9-11]. EEN is now recommended in international guidelines as the primary induction therapy in children and adolescents with active CD [12,13].

Whilst EEN provides an important role, it requires big changes in daily intake and significant support to ensure adherence. A number of other dietary interventions that involve manipulations of standard dietary intake with solid foods have also been considered and evaluated. Examples include the CD exclusion diet, the specific carbohydrate diet (SCD), and the Mediterranean diet (MedDiet) [14,15]. Dietary therapy can be used as a specific intervention in isolation or as an adjunctive treatment in conjunction with a medical intervention for the induction or maintenance of remission. This review focuses specifically on the rationale for the MedDiet and reviews the current data supporting its use by individuals with IBD.

OVERVIEW OF THE MedDiet AND GENERAL HEALTH BENEFITS

The Mediterranean region has been inhabited for many centuries [16]. The regional foods (predominantly plant-based), such as olives, vegetables, fruits, whole grains, nuts, seeds, including several herbs, and food spices, led to the typical dietary patterns seen in the area [17]. The MedDiet can be seen as a way of life that incorporates (but is not limited to) the foods available to and consumed by the people within this region. This way of life is expressed through various skills, rituals, knowledge, social norms, and traditions relating to food cultivation, harvesting, processing, and consumption [18].

From a dietary scheme perspective, MedDiet primarily refers to the dietary patterns of Southern Europe during the period of the 1950s to 1960s [19-22]. The association of MedDiet with low incidence of various chronic diseases and high life expectancy in the region at that time, compared to other parts of the world, led to the Seven Countries Study [18,21]. Findings from this longitudinal study have resulted in further and ongoing interest in this dietary pattern and way of life.

The health benefits of MedDiet have been widely documented. Existing evidence from randomized controlled trials (RCTs), population-based, and prospective epidemiological studies has demonstrated that MedDiet may play a role in the protection against and the management of chronic diseases, including IBD. For example, MedDiet has been shown to improve cardiovascular health [23-27], boost longevity [28,29], reduce cancer risk [30,31], lower the rates of metabolic syndrome [32], improve cognitive function [33,34], and promote gut health [35,36].

COMPONENTS OF THE MedDiet

The MedDiet, as outlined in the early 1960s, was based around plant-based foods (e.g., fruits, vegetables, cereals, nuts, and seeds) that were locally-grown, eaten seasonally and minimally processed [37]. Other features included fruit eaten as the typical dessert, sweets containing concentrated sugars or honey consumed only a few times per week, olive oil as the main source of fat and low to moderate amounts of dairy products (e.g., cheese and yogurt) daily. Other components were low to moderate amounts of fish or poultry, infrequent red meat and low to moderate amounts of wine (notably at mealtimes). This pattern of diet was noted to be low in saturated fat (less than 7%–8%) with a total fat intake ranging less than 20% to more than 35% of total calorie intake. Exercise or other physical activity was also considered important [38].

The modern MedDiet pyramid outlines the range of foods to be included and the frequency of consumption (Fig. 1) [39]. The foundation of this pyramid is based on the frequent inclusion of fruits, vegetables, grains, olive oil, nuts, legumes, seeds, herbs, and/or spices. It is also suggested that fish or seafood be eaten regularly, at least twice each week, and that poultry, eggs, and dairy products be eaten in moderate amounts. Finally, the pyramid suggests that meats and sweets are consumed less frequently.

Fig. 1.

The Mediterranean diet pyramid. This food pyramid outlines the key elements of the Mediterranean diet, with emphasis on foods to be consumed more or less often, along with other life-style aspects. Reproduced with permission from Oldways.

This pyramid gives a concept of serving sizes, and how much of each food should be consumed, adjusting according to individual needs. The quality, rather than quantity, of nutrients is highlighted, for instance unsaturated versus saturated fats, whole versus refined carbohydrates. The model also promotes unprocessed or minimally processed foods, in order to optimize the micronutrient and antioxidant components of foods [20,21]. Moving beyond food and mealtimes, the further holistic concepts of the MedDiet are incorporating physical activity via daily activities and the underlying strong sense of community.

HEALTH BENEFITS OF THE COMPONENTS OF THE MedDiet IN PEOPLE WITH IBD

The combination of varieties of foods (such as olive oil, fruits, vegetables, whole grains, and fish), which form important components of the MedDiet and are critical within the dietary pattern, collectively impacts the health of individuals with IBD. Each component of the MedDiet has important properties that likely contribute to the overall effects [40-43]. The lipid-lowering effect, antioxidative, anti-inflammatory, and immunomodulatory properties, including the ability of some components to influence metabolic health via gut microbiota-mediated pathways, synergistically influence the health and well-being of individuals with IBD [40-43]. A number of studies have explored the effects of the components of the MedDiet in individuals with CD or UC (Table 1) [44-64].

Table 1.

Summary of Studies Exploring the Health Benefits/Effects of the Components of the Mediterranean diet in Individuals with CD or UC

1. Olive Oils

The health benefits of olive oil in individuals with CD and UC appear to stem from its oxidative and anti-inflammatory properties [65,66]. Morvaridi et al. [44] compared the effects of extra virgin olive oil (EVOO) and canola oil (CO) on inflammatory markers and GI symptoms in 40 adults with UC. Both the EVOO and CO groups consumed 50 mL (equivalent to 1,882.8 KJ) per day of uncooked EVOO and CO for 20 days, respectively. At the end of the intervention, erythrocyte sedimentation rate, C-reactive protein (CRP) serum, and GI symptoms (i.e., bloating, constipation, fecal urgency, and incomplete defecation) reduced significantly (P<0.05) in the EVOO group compared with the CO group.

Data arising from experiments using 2 murine models reported similar effects of olive oil on induced colitis [45,46]. In the first experiment, mice were administered sunflower oil (SD), EVOO diet, and unsaponifiable fraction (UF) enriched SD at 5% oil (SD+UF) for 4 weeks before inducing colitis. Compared with the SD group, the disease activity index and microscopic damage score improved significantly in the EVOO and SD+UF dietary groups. Moreover, monocyte chemoattractant protein-1 and tumor necrosis factor-α (TNF-α) levels, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) overexpression, and p38 mitogen-activated protein kinases (MAPKs) activation decreased significantly in the colon mucosa with the EVOO and SD+UF diets [45]. The second study that evaluated the effectiveness of 3 diets (i.e., EVOO, CO, and rice bran oil) on malondialdehyde, myeloperoxidase activity, and interleukin (IL)-1β found a protective effect of these diets on the oxidative and inflammatory status in the setting of dextran sulfate sodium (DSS)-induced colitis. The EVOO diet was, however, superior to the other diets. These findings underscore the beneficial role of olive oil in moderating the inflammatory and oxidative activity in gut inflammation, as seen in UC [46].

Olive oil is rich in monounsaturated fats (MUFAs), especially oleic acid, containing over 77% [67]. MUFAs activate cellular production of proinflammatory mediators, thus modulating immune response in CD and UC [68]. Its role in controlling the activity and intestinal-homing capacity of T cells contributes to an anti-inflammatory effect in active IBD [69]. The antioxidants (such as tocopherol, hydroxytyrosol, and oleuropein) contained in olive oil appear to contribute to lower levels of low-density lipoproteins and increased high-density lipoproteins. These compounds, which modulate gene expression related to the development of atherosclerosis [70], have also been reported to reduce colitis disease activity [47] through an ATF3-dependent anti-inflammatory reprogramming of macrophages [71-73]. High-density lipoprotein reduces free radicals and oxidative stress that may trigger the onset of IBD [74]. It further acts on endothelial cells to inhibit inflammation by reducing nuclear factor (NF)-κB and antagonizing inflammasome activation [75].

2. Fruits and Vegetables

Vegetables and fruits contain vitamins, minerals, and water, and also contain a large proportion of dietary fiber (insoluble and soluble) and phytonutrients [76,77]. Fiber is essential to bowel health and promotes increased satiety. Both soluble and insoluble fibers (acting as prebiotics) contribute to the diversity of the intestinal microbiome in individuals with IBD. Insoluble fiber also functions as a bulking agent, giving protection against colorectal cancer, which may develop in individuals with ongoing uncontrolled colitis [78,79]. Bacterial fermentation of fiber is linked with the production of short-chain fatty acid (SCFA) metabolites that are beneficial to gut health and microbiome homeostasis [76,80].

Several studies demonstrate that consuming certain fruits, such as apples, bananas, and orange juice that have a lower fiber content, during remission after a medical treatment could provide a protective immune-modulating effect in preventing IBD recurrence [81-83]. In addition, soluble fiber fraction in certain vegetables, such as broccoli, prevents relapse in patients with CD [84]. Available evidence suggests that the consumption of vegetables such as zucchini, potatoes, carrots, eggplants without skin, green beans, and chard, which have a low content of insoluble fibers, could be advised for patients with CD during remission [84].

Pomegranate, another fruit known to be high in polyphenols, was recently evaluated in a placebo-controlled RCT involving 16 patients with either CD or UC in stable clinical remission [48]. The active group who consumed 125 mL of pomegranate juice twice daily was shown to have lower fecal calprotectin (FC) and endotoxin levels after 12 weeks of treatment, along with other positive benefits, compared to the control (placebo). However, the reduction in plasma endotoxin level was greater but variable in those with UC, unlike those with CD, who showed a more uniform but less pronounced response. This finding suggests the potential benefit of pomegranate fruit for the maintenance of remission of CD or UC.

Prebiotic foods, which contain soluble fibers, have been shown to help in maintaining eubiosis [4,85]. Prebiotics (mainly fructooligosaccharides [FOS], glucooligosaccharides [GOS], lactulose, inulin, and derivatives of galactose and β-glucans) [86], as major components of fruits and vegetables, have been widely studied in people with IBD. While there are conflicting findings regarding the role of these plant components in IBD, many studies have shown protective effects. An open-label, multicenter clinical trial using germinated barley foodstuff (GBF) treatment in 21 adults with UC reported a significant reduction in clinical disease activity in the GBF group compared with the non-GBF group after 4 weeks [49]. Another RCT noted a significant decrease in FC, as a biomarker of inflammation, in the intervention group after a 2-week supplementation with inulin enriched with FOS [50]. A more recent study by Valcheva et al. [51] found a significantly higher clinical response and remission rate among patients with UC who received high-dose oligofructose-enriched inulin for 9 weeks. Similarly, an evaluation of 1-ketose in individuals with mild to moderately active UC demonstrated reductions in disease activity [52].

Conversely, an RCT that assessed the impact of FOS on 50 people with active CD observed adverse clinical outcomes and an insignificant difference in fecal microbiota concentration between the CD and control groups [53]. Hafer et al. [54] found no positive effect of oral lactulose on clinical, endoscopic, and histopathological activity in both CD and UC, except improvement in the quality of life of those with UC. Despite these contradictory findings on the effects of prebiotics, the benefits of other components of fruits and vegetables in supporting functions in CD and UC remain indisputable. For example, the phytonutrients (mainly phenolics, flavonoids, anthocyanins, phytosterols, polyphenols), which are common in fruits and vegetables, offer protection against oxidative stress and inflammation, which may serve to prevent or delay chronic degenerative diseases and associated abnormalities [87]. On the other hand, carotenoid lycopene in tomatoes and other red fruits reduces inflammation by inhibiting the production of proinflammatory cytokines, modifies the immune response signaling pathways, and combats reactive oxygen species, thus lowering the oxidative stress and reducing cellular damage, which are key features in the etiology of IBD [88].

3. Whole Grains, Nuts, and Legumes

In addition, whole grains, nuts, and legumes, which constitute a staple source of nutrition in the traditional MedDiet, are rich in protein, phytochemicals, fiber, iron, and B vitamins [89,90]. Altogether, consumption of whole grains and legumes are known to result in an increase in anti-inflammatory butyrate-producing bacteria, enhance gut microbiome diversity, and reduce proinflammatory bacteria [91]. The phytochemicals found in these foods may be responsible for some of their anti-inflammatory and antioxidant effects [92]. A large prospective cohort study involving 223,283 adults with over 5,460,315 person-years of follow-up showed that a higher intake of nuts decreased the risk of CD in overweight or obese individuals [55]. Further, a Canadian observational study observed that higher intake of vegetables and whole grains reduced CD risk, while consumption of more fruit and legumes was associated with a reduced risk of UC [56]. However, high consumption of refined grains was associated with increased risk of developing UC or CD [56]. A low-fat, high-fiber diet, derived from whole grains, nuts, seeds, and legumes, has been shown to decrease markers of inflammation and reduce intestinal dysbiosis in individuals with UC, offering insight into dietary interventions that might benefit people with UC in remission [57].

4. Fish, Poultry, and Dairy Products

Other essential components of the MedDiet, such as fish, poultry, and dairy products, provide protein, vitamin B₁₂, calcium, and iron, which are vital for metabolic processes and maintaining muscle mass in individuals with IBD [93]. While red processed meat is known to increase inflammation and may worsen IBD symptoms, diets low in red and processed meat appear to reduce symptoms in people with UC but not those with CD [58,59]. Dairy products, especially yogurt and fermented dairy foods like kefir, have been found to increase the gut microbial diversity and improve the quality of life for individuals with CD or UC [60]. The use of probiotics (e.g., Lactobacillus rhamnosus) in addition to a MedDiet has been shown to alter the composition of the microbiota, thus allowing a return to eubiosis [4]. Studies involving the consumption of other dairy products in people with IBD are inconsistent due to lactose intolerance, adverse effects of the long-chain triacylglycerol, or allergy to milk proteins, especially in individuals with CD [94]. Komperød et al. [61] reported dairy and wheat products to be the major triggers of symptoms in individuals with UC in clinical remission. Sheep and goat’s milk may, thus, offer a good alternative for people with CD who do not tolerate bovine milk [95].

5. Herbs and Spices

Herbs and spices provide unique flavors and tastes but also provide potential health benefits [96]. These plants contain various important bioactive compounds (e.g., flavonoids, polyphenols, alkaloids, tannins, phenolic diterpenes, and sulfur-containing substances). These compounds have antioxidant and anti-inflammatory effects, which positively impact outcomes [97-99]. Curcumin, for example, a very important bioactive compound of turmeric, widely used in modern Mediterranean cuisine, elicits anti-inflammatory effects mediated via immune cellular function regulation, cytokine inflammatory inhibition, and suppression of the NF-κB signaling pathway [100,101]. In addition, curcumin plays a vital role in reducing oxidative stress, another aspect of the pathophysiology of IBD [100,101].

A multicenter RCT found a significant reduction in clinical disease activity and endoscopic parameters, higher remission rates, and anal lesion healing in patients with CD treated for 4 weeks with synthesized curcumin derivative Theracurmin [62]. Likewise, Hanai et al. [63] reported a significant improvement in the clinical activity index and endoscopic index in patients with quiescent UC after 6 months of curcumin. A 6-month follow-up observed no significant difference in relapse rates between the curcumin and placebo groups, indicative of longer-term maintenance of remission. Although there is growing evidence around the potential medicinal role of curcumin as a treatment for IBD, its unique limitation in bioavailability and rapid metabolism remains an obstacle. Combination therapies and nano-formulations are under investigation to mitigate this challenge; however, robust studies are needed to support these findings.

6. Wine Products

In addition, wine as a key component of the MedDiet, is also rich in phytochemicals (similar to fruits and olive oil). In in vitro and in vivo studies, the high polyphenolic content of wine is believed to counteract oxidative stress and provide anti-inflammatory properties essential in ameliorating symptoms in people with UC [102]. A few studies have linked the consumption of red wine to a decrease in inflammatory markers and intestinal permeability in individuals with UC or CD [64]. Swanson et al. [64] assessed the effects of moderate daily consumption of red wine in 21 people with inactive CD and UC. After 1 week, there was a significant decrease in FC and an increase in intestinal permeability in both cohorts. However, no significant difference was observed in either clinical disease activity scores or CRP levels [64]. While FC reduction (possibly due to anti-inflammatory effects) is suggestive of symptom improvement in CD or UC, the elevated intestinal permeability poses a long-term risk of disease relapse. Additionally, a case-control study found improvement in clinical status and intestinal symptoms in individuals with active UC following a moderate consumption (250 mL/day) of red wine.98 Although these findings appear promising, further research is necessary to elucidate whether these changes can be attributed to wine specifically.

THE EFFICACY OF MedDiet IN THE INDUCTION AND MAINTENANCE REMISSION OF ACTIVE CD OR UC

Positive outcomes in several chronic diseases, including IBD, have been linked to the MedDiet or its components [103-107]. Although there are few data to currently support the recommendation of the MedDiet for the induction of remission and maintenance of remission in patients with CD or UC, adherence to MedDiet pattern has been associated with beneficial outcomes in active CD or UC, likely due to the synergistic effects of nutrients.

When remission is achieved, the next goal is to maintain long-term remission [108]. Besides nutrient replacement, dietary management plays a vital role in preventing relapses after remission. Several nutritional interventions have shown promising results in providing longer-term benefits in the maintenance of remission and prevention of disease complications. Preliminary data suggest MedDiet may contribute to the maintenance of remission in CD or UC. A number of studies have evaluated MedDiet in individuals with CD (Table 2) [109-111], while others have focused on individuals with UC (Table 3) [112-115]. In addition, several reports have included groups of IBD, without subgroup analyses (Table 4) [116-118].

Table 2.

MedDiet in the Induction and Maintenance of Remission of Active CD

Table 3.

MedDiet in the Induction of Remission and Maintenance of Remission of Active UC

Table 4.

MedDiet in the Induction and Maintenance of Remission of Active CD and UC

An RCT reported no difference in outcomes (symptomatic remission) among adults with CD after receiving the MedDiet or SCD for 12 weeks [109]. Symptomatic remission rates were similar: 46.5% of those on the SCD and 43.5% on the MedDiet reported improvement. It was suggested that due to the ease of following the MedDiet, together with its other associated health benefits, a MedDiet may be preferred over the SCD for most patients with mildly-moderately active CD [109].

A large American RCT, the Diets to Induce Remission of CD (DINE-CD), found similar remission rates in patients with active CD within 6 weeks of receiving either the MedDiet or the SCD [15]. A reduction of 50% or more in FC levels was seen in 30% of patients with elevated FC at baseline. A similar decrease in FC levels was observed in a cross-sectional study that evaluated the adherence to a MedDiet in children with CD [110]. This study demonstrated that the consumption of an additional 0.9 portions of vegetables per day during remission was beneficial.

Similarly, a prospective non-randomized study investigated the efficacy of a plant-based, semi-vegetarian diet (i.e., a MedDiet-like diet) for the maintenance of clinical remission in a small group of people with CD [111]. All 16 patients in the intervention group remained in clinical remission after 12 months. Only one patient relapsed after 2 years. This study suggests that a semi-vegetarian diet (rice, fruits, vegetables, beans, dairy products, and eggs), which is a key component of the MedDiet, may be effective in preventing relapse in CD.

Erol Doğan et al. [112] evaluated the effect of MedDiet supplemented with curcumin or resveratrol in patients with UC with mild to moderate symptoms in 3 clinics in Turkey. Participants were allocated to 1 of 3 groups: a control group that received MedDiet, a second group that received MedDiet+curcumin, and a third group that received MedDiet+resveratrol for 8 weeks. All the interventional groups underwent nutrition education on the MedDiet pyramid and recommendations on portion and frequency [112]. At the end of the interventions, all 3 regimens were effective in reducing clinical disease activity, inflammation, and improving quality of life. However, no significant difference was found in the effect on the assessed parameters between the groups. This finding shows that even without supplementation with curcumin or resveratrol, adherence to MedDiet alone can resolve symptoms and improve quality of life in people with UC. The sole attribution of MedDiet to these effects is, however, limited by the study’s small sample size. Incorporating MedDiet as part of the IBD treatment approach could potentially enhance patients’ outcomes that would not be achieved by pharmacological therapies alone.

An observational prospective study followed up adults with UC for 8 years following pouch surgery to assess the impact of adherence to MedDiet on disease activity and inflammatory markers (FC and CRP) [113]. Patients with higher MedDiet score (≥5), characterized by increased consumption of dietary fibers, vitamins, minerals, and antioxidants had normal CRP and lower FC. Additionally, higher adherence to MedDiet was associated with a lower rate of pouchitis. Upon further analysis of several specific nutrients, only higher caffeine intake was associated with lower FC levels. The authors emphasized that the composite benefits of MedDiet appear to be higher than the effects of individual nutrients. Overall, these findings demonstrate the potential role of MedDiet in modulating the inflammatory pathways and maintaining remission long after pouch surgery.

An animal study compared the impact of a MedDiet fat blend to 3 other distinct dietary patterns in mice known to develop colitis spontaneously [114]. The diets were characterized as a MedDiet fat blend (high MUFA, 2:1 n-6:n-3 polyunsaturated fatty acid [PUFA] and moderate saturated fat), corn oil (CO, n-6 PUFA-rich), olive oil (MUFA-rich) and milk fat (saturated fat rich). Mice receiving the MedDiet had lower clinical and histopathological scores than those receiving the other diets. Moreover, the use of the MedDiet in this study was associated with more beneficial microbes and less colitogenic microbes such as Akkermansia muciniphila. Higher cecal acetic acid levels were also demonstrated. In contrast, mice receiving the CO diet had a higher prevalence of mucin-degraders associated with colitis, including A. muciniphila and Enterobacteriaceae. Overall, these positive findings suggest that the MedDiet fat blend could be incorporated into a maintenance diet for colitis.

In a recent Canadian RCT, the effect of the MedDiet was evaluated in patients with quiescent UC [115]. Subjects were assigned to the MedDiet or the habitual Canadian diet. After 12 weeks of the intervention, those receiving the MedDiet had better maintenance of low FC than the control group. Higher levels of SCFA were seen in those managed with the MedDiet. These data further support the MedDiet as a sustainable diet pattern to maintain remission in individuals with UC.

One interventional study evaluated the impact of the MedDiet on disease activity, obesity, obesity-related complications, and quality of life (QoL) in individuals with CD and UC [116]. The authors noted improved QoL and anthropometric markers (body mass index and waist circumference) and less liver steatosis after 6 months of the MedDiet dietary intervention. Reduced disease activity and inflammatory markers were seen concurrently in this cohort. This report suggests that MedDiet not only improves disease activity but also corrects nutritional status and improves metabolic health in individuals with IBD.

Furthermore, an Egyptian RCT evaluated the efficacy of the MedDiet in 100 children and adolescents with moderately active CD and UC receiving treatment at Tanta University Hospital [117]. Participants were randomized to receive the MedDiet intervention (KIDMED score ≥ 8) or to continue with their regular diet over 12 weeks. There were significant improvements in the clinical scores and inflammatory markers in both groups following the intervention. The young people receiving the MedDiet intervention, however, had larger reductions in clinical disease activity scores and inflammatory biomarkers (including FC).

Similarly, Strisciuglio et al. [118] reported a significant association between higher adherence to MedDiet and reduced FC levels in children with CD and UC in clinical remission. Comparative analyses between the 3 groups revealed that the Med-Diet was well tolerated. There were differences in intake of protein (P=0.047), vitamin D (P=0.044), and iron (P=0.023) in the group with CD compared to those with UC. This suggests that MedDiet is well accepted by children with IBD and that it may have a beneficial effect of reducing intestinal inflammation.

THE POTENTIAL MECHANISMS OF ACTION OF THE MedDiet IN CD and UC

The precise mechanisms by which the MedDiet enables benefits in individuals with IBD have not yet been fully elucidated. Some putative mechanisms include the direct effect of dietary antigens, altered gut permeability, and the autoinflammatory response of the mucosa due to changes in the microbiome [119]. Some evidence indicates that dietary patterns modulate key pathways such as NF-κB, oxidative, and endoplasmic reticulum stress pathways [120-122]. Furthermore, dietary patterns represent one of the key determinants of the composition of the human intestinal microbiome [123].

1. The Anti-Inflammatory Mechanisms of MedDiet

The MedDiet provides an abundance of plant-derived polyphenols, which have anti-inflammatory and antioxidant properties [124]. Two RCTs demonstrated the effects of these polyphenolic properties on individuals with UC, with resveratrol showing marked improvement in disease activity and QoL due to elevated antioxidant capacity and a reduction in oxidative stress [125,126]. Further, Pycnogenol, a plant extract rich in polyphenols, was potent in reducing oxidative stress in children with CD in clinical remission [127].

Polyphenols, a diverse group of phytochemicals found in various foods (e.g., vegetables, fruits, nuts, tea, and wine) within the MedDiet profile, are known to impact IBD progression through multiple biological pathways. Polyphenols exert antioxidant and anti-inflammatory effects, which are implicated in the pathophysiology of CD and UC, through a modulatory mechanism that involves cellular signaling pathways and transcription factors [128]. There is also accumulating evidence supporting the role of polyphenols in modulating the gut microbiome, which ultimately restores metabolites to repair and maintain the disrupted gut homeostasis in IBD. At the molecular level, via cellular signaling pathways and transcription factors, polyphenols inhibit NF-κB through several mechanisms resulting in inhibition of proinflammatory cytokine production and other gene expression products involved in inflammation [129,130]. Polyphenols increase endogenous antioxidant defense and phase II xenobiotic metabolism through activation of NF erythroid 2-related factor (Nrf)2 [131]. Activation of farnesoid X receptor (FXR) by polyphenols increases the production of antimicrobial peptides (e.g., cathelicidin), enhances tight junction (TJ) protein structure, and inhibits NF-κB [132]. Activation of aryl hydrocarbon receptor by polyphenols increases expression of phase II xenobiotic metabolism enzymes, which are crucial in promoting regulatory T cell differentiation and suppressing proinflammatory cytokine production [133-135].

The anti-inflammatory properties of olive oil, a key component of the MedDiet, are in part due to nonsteroid anti-inflammatory drug-like effects [136]. Olive oil and its biophenols lead to reduced levels of COX-2, metalloprotease, and IL-6 [137,138]. Most dietary polyphenols reach the intestine, where they are either absorbed or are biotransformed, enabling local effects on the intestinal microbiome and epithelium. Studies have also shown that the consumption of EVOO leads to improvements in other markers of inflammatory, oxidative, endothelial, and general metabolic status [65,66].

Another study evaluated the effects of hydroxytyrosol, a bioactive compound found in olive oil [139]. Hydroxytyrosol resulted in anti-inflammatory effects on murine macrophages exposed to lipopolysaccharide, with reduced production of proinflammatory cytokines (e.g., IL-6) and inflammatory mediators nitric oxide and prostaglandin E2 via inhibition of the NF-κB pathway [140]. Interestingly, analogous findings were reported in studies ascertaining the effects of wine polyphenols, with similar modulation of intracellular signal transduction pathways [141]. Together, these show that these 2 components of the MedDiet appear to provide similar beneficial anti-inflammatory, antioxidative, and immune-modulatory effects.

The MedDiet was shown to be associated with the methylation and regulation of various inflammation-related genes [142]. Adherence to the MedDiet has been correlated with a decrease in inflammatory markers and flares of IBD [143,144]. Moreover, studies have revealed the potential role of the MedDiet in modulating gene expression, reducing inflammatory markers, and normalizing the microbiota with positive effects on disease outcomes. [145].

Other experimental work has further elucidated the effects of olive oil extracts on the pathophysiology of UC [137]. Short-term culture of explants obtained endoscopically from individuals with UC were utilized in the first phase of these studies [95]. The explants were challenged with lipopolysaccharide from Escherichia coli, in the presence or absence of oleuropein (OLE). OLE treatment resulted in lower expression of IL-17 and COX-2. Furthermore, the OLE-treated colonic samples showed signs of mucosal healing, with reduced infiltration of CD3, CD4, and CD20 cells [137].

In a second study, the researchers first examined the antiinflammatory effects of olive leaf extract (0.5–25 mg/kg), which contained more than 80% OLE, in 2 murine models of colitis (DSS and DNBS). Later, they also evaluated the immunomodulatory effects of an olive leaf extract in ex vivo colon cultures utilizing mucosal biopsies from patients with CD. In both colitis models, the olive extract reduced the expression of proinflammatory mediators (IL-1β, TNF-α, and iNOS) and improved the intestinal epithelial barrier by restoring the expression of ZO-1, MUC-2, and TFF-3. These effects were confirmed in the ex vivo model, where the olive extract reduced the production of proinflammatory mediators (IL-1β, IL-6, IL-8, and TNF-α) [146].

Overall, the evidence produced through these in vitro studies illustrates a clear effect of olive oil phenols on major inflammatory pathways. The commonly observed effects were inhibition of p38/MAPK, NF-κB, and iNOS. Therefore, in vitro evidence reveals how olive oil, and the phenols as a key component of the MedDiet can modulate several key points relevant to IBD pathophysiology.

Omega-3 PUFAs, found in abundance in oily fish, are another key component of the MedDiet that also exhibit anti-inflammatory effects. These compounds have various positive effects, including improved intestinal epithelial barrier in UC [124,147]. PUFAs exhibit anti-inflammatory properties that are known to modulate immune responses and reduce proinflammatory cytokine production, to alleviate intestinal symptoms in individuals with CD and CU [148,149]. Of note, a combination therapy of fish oil and mesalazine administered rectally suggests a new direction for UC treatment [150].

Furthermore, the majority of the MedDiet is naturally gluten-free, comprising nutrient-dense foods like legumes, vegetables, fruits, nuts, fish, meat products, buckwheat, corn, oats, rice, and quinoa. Gluten may promote inflammatory responses in the GI tract therefore, avoidance of dietary gluten may be beneficial [151,152].

2. MedDiet in the Modulation of the Intestinal Microbiome and Metabolites

Dysbiosis is typically present in people with IBD [153-156]. Overall, the adoption of the MedDiet is associated with greater microbial diversity [124]. Dietary fiber, as one of the main components of the MedDiet, influences the composition of the intestinal microbiome [157]. In particular, this prompts the establishment and maintenance of a healthy and diverse microbiome with associated improved host immunity [124,158,159]. Dietary fiber within the MedDiet includes “microbiota-accessible carbohydrates,” complex carbohydrates found in fruits, vegetables, legumes, and whole grains. These compounds are associated with the growth of butyrogenic and other helpful species [124,160].

Recent studies further support these outcomes. In a study of well first-degree relatives of people with CD, adherence to the MedDiet was associated with a higher proportion of fiber-degrading bacteria belonging to the Firmicutes and Bacteroidetes phyla, along with increased fecal levels of SCFAs [161,162]. Further, a reduction of FC levels was also seen in this group.

A study involving 8 adults with CD managed for 6 weeks with a “Mediterranean-inspired diet,” (including salmon, avocados, sweet potatoes, various vegetables, EVOO, green tea, honey and fish oil capsules) demonstrated significant changes in microbial gene expression [145]. Metagenomic analysis showed altered expression profiles of more than 3,000 intestinal microbial genes, with cumulative effects suggestive of a microbial composition resembling healthy controls. These metagenomic changes were associated with altered bacterial patterns, namely decreased abundance of Proteobacteria and Bacillaceae and increased abundance of Bacteroidetes [145].

The essential microbial metabolites produced mainly by the Firmicutes and Bacteroidetes phyla through fermentation of dietary fibers are recognized to mediate several beneficial processes, including enhanced barrier function and immunomodulatory effects [163]. Among the microbially-derived metabolites with mechanistic roles in IBD are bile acid derivatives, SCFAs, and tryptophan. Mechanistically, SCFAs mediate intestinal homeostasis through several pathways. They promote the expansion of regulatory T (Treg) cells, which are crucial in the host immune response [164]. They catalyze energy metabolism in the intestinal epithelium, thus energizing the colonic mucosa cells, and support epithelial barrier function by increasing TJ proteins and mucin production [165]. The metabolite also modulates the intestinal pH and production of antimicrobial peptides (e.g., cathelicidin), which limit the colonization of enteric pathogens [166,167]. Both butyrate and propionate mediate an anti-inflammatory response in the gut via peripheral Treg cell differentiation, in an extrathymic pathway dependent on CNS1 [168,169].

The modification of approximately 5% of bile acids that escape enterohepatic circulation into secondary bile acids by intestinal microbes presents important biological functions in intestinal homeostasis [170]. The secondary bile acids modulate intestinal immune response and expression of TJ proteins, and also produce antimicrobial effects through FXR activation [171,172]. Functionally, the MedDiet restores eubiosis and ameliorates intestinal symptoms in individuals with IBD through remodeling of the gut microbiome, which mediates and maintains intestinal homeostasis, via complex immunemetabolite signaling pathways.

Beyond the metabolomic effects produced, some gut microbiota involved in IBD pathogenesis, for example, Faecalibacterium prausnitzii are known to activate a 15 kDa protein with anti-inflammatory properties [173]. This protein inhibits the NF-κB pathway in intestinal epithelial cells and prevents DNBS-induced colitis in mice [173]. Gut microbiota modulate the autophagy-related pathways and Akt/PI3K//mTOR signaling in host cells [174]. Autophagy proteins prevent intestinal inflammation by supporting Paneth cell homeostasis and viability, by controlling endoplasmic reticulum stress pathways, and by secreting antimicrobial proteins to reinforce intestinal epithelial barrier functions [175-177]. In addition, the microbiota associated with IBD promotes mucosal healing through the induction and release of TNF-like ligand 1A (TL1A) by CX3CR1+ mononuclear phagocytes (MNPs), which powers the production of group 3 innate lymphoid cells and IL-22, leading to the restoration of the mucosal lining of the GI tract during acute colitis [178].

Further, the divergent gut microbiota community, particularly bacteria and fungi, regulates immune and cellular mechanisms that protect barrier integrity (e.g., IL-17, IL-22, and mucus production) and inflammation (e.g., IL-10 production). The fungi, Candida albicans, produces the toxin candidalysin that induces intestinal inflammation by damaging epithelial membranes and activating the MAPK pathway, leading to the recruitment of T helper 17 (Th17) cells, neutrophils, and proinflammatory cytokines [179-182]. Two species of the actinobacterium phylum prevalent in the human gut induce Th17. The species Eggerthella lenta activates Th17 by lifting inhibition of the Th17 transcription factor Rorγt through cell- and antigen-independent mechanisms [183], while Bifidobacterium adolescentis stimulated the production of Th17 cells in an antigen-specific manner [184,185]. The Th17 cells produced by both bacteria and fungi are known to impact barrier function via IL-17 [186-188]. Both CD and UC are strongly associated with Th17 cells [189]. TH17 affects the development of IBD both negatively and positively. Th17 cells shield the intestinal/epithelial lining and maintain gut homeostasis via follicular helper T-cell phenotyping, which in turn activates B cells to produce T-cell-dependent host-protective IgA antibodies [190]. IL-17A secreted by Th17 cells reinforces the tight connections between intestinal epithelial cells by activating claudin expression, collaborates with fibroblast growth factor 2 to repair the damaged intestinal epithelium through Act1-mediated direct signal crosstalk, and instructs goblet cells to secrete mucin, all protecting the gut [191-193]. IL-17 and IL-22 have been shown to prevent the development of severe colitis, suggesting their roles in the pathophysiology of IBD [194,195].

Contrarily, excessive activation of Th17 cells can exacerbate IBD outcomes via several mechanisms [196]. Th17 cells induce inflammation through autoreactivity during differentiation and migration to the intestine. In an inflamed setting, apoptotic cells trigger the histocompatibility complex II to deploy autoantigens. This ignites the differentiation of autoreactive Th17 cells, leading to autoinflammation and autoantibody production [197]. However, recent findings suggest that arginine, an amino acid found in various protein-rich foods within the MedDiet, can alleviate this Th17 limitation: a new insight that supports the role of diet as a noninvasive way to enable manipulation of microbial immunomodulation [189].

MedDiet ADOPTION OUTSIDE THE MEDITERRANEAN REGION

The health benefits of MedDiet in the prevention and management of chronic diseases, including IBD, are undeniable though not fully elucidated. However, because the MedDiet is a food culture predominant in Mediterranean region, its successful adoption outside this region may require adaptations to suit local dietary and cultural patterns. Every community has its sustained habitual dietary patterns that are influenced by societal upbringing, food beliefs, culture, food systems, and generational knowledge or patterns. Adopting a novel dietary pattern that deviates from such norms often faces resistance [198]. Thus, recognizing potential barriers to adoption is critical for the success of any nutritional intervention across regions. Although confronting these shortcomings may appear challenging, gaining experience and applying knowledge from other nutritional programs, where similar barriers have been successfully addressed, could yield effective results [199,200]. Haigh et al. [199] and Moore et al. [200] provided insights into the need to strengthen dietary education, particularly around the health benefits of MedDiet components, including organizing practical food preparation and tasting sessions to unlock the misconceptions and improve MedDiet acceptability in a new setting. Routine advice or information sharing through various platforms should align with diverse cultural food practices and indigenous food views. In addition, incorporating culturally sensitive, locally available alternative recipes or food varieties that are easy to prepare and have nutrient profiles similar to those in MedDiet components is advisable. For example, recommending frozen or canned foods for those in temperate regions instead of seasonal fresh products could enhance accessibility and improve adoption of MedDiet in colder climates. Providing client-centered budgeting tips would alleviate the fear that the MedDiet is costly and increase its uptake [201].

Furthermore, MedLey, HELFIMED, and SMILE RCTs evaluated the uptake of MedDiet among individuals with depression, mental illness, and cardiovascular risk [202-207]. In these trials, personalized dietary advice was provided one-on-one or through community groups by qualified dietitians and volunteers. Routine counselling sessions were held in addition to other services and material supports such as goal setting, meal planning, mindful eating, food hampers, and recipes given to participants. There was high adherence to the MedDiet, with 90% adherence at the end of the trials. Replicating successful models like these could establish the MedDiet concept and sustain its adherence across regions.

Moreover, for MedDiet to be fully embraced in countries outside the Mediterranean, concerted efforts from key stakeholders, such as health professionals, researchers and policymakers, are needed [201]. Despite the potential obstacles surrounding the adoption of MedDiet across regions, there are indications that MedDiet is well tolerated in both adults and children with IBD around the world [118,208-210].

CONCLUSIONS

This review aimed to summarize the current evidence concerning the putative role of the MedDiet in the management of IBD. Numerous in vitro and animal studies indicate that the MedDiet might have a role in reducing and maintaining remission. The mechanisms of these benefits include modulation of the intestinal microbiome and metabolites, along with antioxidative, anti-inflammatory, and immunomodulatory effects. A small number of clinical studies involving individuals with IBD have shown promising results, with excellent adherence and safety profiles.

Further data are required to more fully support the roles of the MedDiet in the induction or maintenance of remission in individuals with IBD. Such works should focus on individual IBD subtypes (CD or UC) as the effects of the MedDiet appear to have differential effects between these subtypes. Firstly, further work is required to elaborate on the underlying mechanisms of the specific components of the MedDiet. These endeavors may focus on elaborating dose-responses and consider the impact of co-dependent effects. The outcomes of such work may assist in understanding the pathophysiology of IBD.

Secondly, additional RCTs should focus on substantiating the current findings on the role of the complete MedDiet in key clinical settings, such as the induction of remission, maintenance of remission, and possibly maintenance of health in first-degree family members at increased risk of developing IBD. Such endeavors will provide additional strength to personalized nutrition and perhaps to wider public health recommendations.

Furthermore, future research is also needed to assess the role of the MedDiet in combination with other interventions, including medical therapies, and to establish how the concepts of the MedDiet might be adapted to countries or regions with other local food sources. These considerations withstanding, the current evidence clearly sets the scene for the MedDiet to have a clear role in the management of IBD.

Notes

Funding Source

The research activities of AS Day are supported by Cure Kids.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Data Availability Statement

Data sharing is not applicable as no new data were created or analyzed in this study.

Author Contributions

Conceptualization: Brown SC, Day AS. Methodology: Acire PV, Day AS. Supervision: Day AS. Writing - original draft: Acire PV. Writing - review & editing: Acire PV, Brown SC, Day AS. Approval of final manuscript: all authors.

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Author (year)	Country	Design	Population (CD/UC)	Exposures and sample size	Study duration	Outcomes of interest	Impact on CD/UC
Morvaridi et al. (2020) [44]	Iran	Single blind, cross-over RCT	Adults with UC (n=40)	50 mL/day of uncooked EVOO or CO	3 wk	Inflammatory markers and GI symptoms	Reduced ESR, CRP, and GI symptoms in EVOO group (P<0.05)
Sánchez-Fidalgo et al. (2013) [45]	Spain	Animal model	Induced colitis	20 EVOO, 20 SD, and 20 SD+UF	6 wk	DAI, microscopic damage score, signaling and inflammatory proteins	DAI improved with EVOO or SD+UF (P < 0.001); reduced microscopic damage score in EVOO and SD+UF groups
Tanideh et al. (2020) [46]	Iran	Animal model	Induced colitis	9 Groups, comprising 5 mL/kg of EVOO, CO, RBO, EVOO+G, CO+G, or RBO+G	10 day	Colonic MDA, MPO activity, and IL-1β levels	EVOO suppressed MDA, MPO activity, and IL-1β
Wang et al. (2025) [47]	China	Prospective cohort and experimental	Adult CD (n = 94), UC (n = 79), HC (n = 69)	Animal model in addition	4 yr	Effect of HDL on disease activity	Elevated HDL via CETPi reduced disease activity
Minato et al. (2025) [48]	Italy	RCT	Adults with inactive CD (n = 6) or UC (n = 10)	Disease and placebo groups received 125 mL of POMJ twice daily	12 wk	FC and plasma endotoxin	FC decreased 2.4-fold (P=0.033) while plasma endotoxin levels reduced in the POMJ group compared to baseline
Kanauchi et al. (2003) [49]	Japan	Open-label RCT	Adults with mild to moderate active UC	Control (n = 7) and GBF (n = 11). Controls received ant-inflammatory treatment and GBF 20–30 g/day	4 wk	CAI and fecal microbiome	Decreased CAI scores compared with the controls (P < 0.05). Fecal concentrations of Bifidobacterium and Eubacterium limosum increased
Casellas et al. (2007) [50]	Spain	RCT	Adults with active UC (n = 19)	FOS-enriched inulin (12 g/day) vs. placebo (maltodextrin)	2 wk	Mucosal inflammation	FOS-enriched inulin led to reduced FC (P < 0.05)
Valcheva et al. (2019) [51]	Canada	RCT	Adults with mild to moderate UC (n = 31)	Randomized to 7.5 g or 15 g FOS/inulin	9 wk	Clinical activity, FC, and gut microbiome composition and function	Reduced colitis in high-dose group (P=0.04). Increased abundance of key bacterial species in high-dose group
Ikegami et al. (2023) [52]	Japan	RCT	Adults with mild to moderate UC (n = 40)	1-Kestose or placebo (maltose)	8 wk	CAI, clinical remission and response rates, and microbiome diversity	1-Kestose led to lower CAI (P=0.026), higher clinical remission and response (P < 0.05), and reduced alpha-diversity
Benjamin et al. (2011) [53]	UK	RCT	Adults with CD (n = 103)	FOS (n = 54) or placebo (n = 49).	4 wk	Clinical response, microbiome analyses	No differences in clinical response or microbiome
Hafer et al. (2007) [54]	Canada	RCT	Adult CD (n = 17) and UC (n = 14)	10 g/day lactulose vs. standard therapy	16 wk	Clinical disease activity, QoL index, immunohistochemical parameters.	No difference in CAI or endoscopic scores. QoL improved in patients with UC (P=0.04)
Lopes et al. (2025) [55]	USA	Prospective cohort	Adults from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study	223,283 Participants	31 yr (5,460,315 person-years of follow-up)	CD and UC risk	Nut and legume intake was not associated with CD/UC risk. Higher intake was protective in obese CD/UC
DeClercq et al. (2018) [56]	Canada	Cross-sectional study	Middle age and older adults from Atlantic PATH study	12,802 Participants (n = 12,568 without IBD, n = 234 with IBD)	12 mo	Diet quality and risk of CD/UC in obese participants	Increased intake of vegetables and whole grains reduced the risk of CD. UC risk reduced with higher intake of fruit and bean/legumes. Refined grains increased CD/UC risk
Fritsch et al. (2021) [57]	USA	RCT	Adults with UC in remission (n = 26)	LFD (10% of calories from fat) vs. iSAD (35%–40% of calories from fat)	4 wk + 2 wk wash-out period	CAI, QoL, inflammatory markers and microbiome and metabolome parameters	Inflammatory markers decreased, relative abundance of microbiota and anti-inflammatory markers increased (P < 0.05)
Albenberg et al. (2019) [58]	USA	RCT	Adults with CD in remission (n = 213)	Low meat (not > 1 serving of meat/month) vs. high meat (minimum of 2 servings/wk)	49 wk	CD symptom relapse	Consumption of processed red meat was not associated with symptomatic relapse
Jowett et al. (2004) [59]	UK	A prospective cohort	Patients with UC in remission	191 Patients	12 mo	UC relapse	52% relapsed, consumption of red processed meat, alcohol, and protein increased the likelihood of relapse
Yilmaz et al. (2019) [60]	Turkey	Open-label RCT	Adults with IBD in remission (n = 45)	25 Treatment group (10 CD and 15 UC) and 20 control group (10 CD and 10 UC). Each consumed 800 mL/day kefir	4 wk	Abundance of intestinal microflora and quality of life	Kefir significantly increased the microbiota load and improved QoL in both UC and CD
Komperød et al. (2018) [61]	Norway	RCT	Adults with CD in clinical remission (n = 16)	Habitual diet + wheat and dairy products for 2 wk, then 2 wk of strict elimination diet	4 wk	CD symptom severity	All symptoms improved (P < 0.05) during the elimination diet period
Sugimoto et al (2020) [62]	Japan	Multicenter RCT	Adults with mild to moderate CD (n = 30)	Theracurmin 360 mg/day vs. placebo	12 wk	Clinical and endoscopic remission, healing of anal lesions, and inflammatory markers	Reduction in clinical disease activity in Theracurmin group (P=0.005), higher clinical remission rate (P=0.020), reduction in endoscopic severity (P = 0.032), and healing of anal lesions (P=0.017)
Hanai et al. (2006) [63]	Japan	Multicenter RCT	Adults with quiescent UC (n = 89)	Curcumin+standard treatments vs. placebo	6 mo	CAI and EI	Curcumin improved CAI (P=0.038) and EI (P=0.0001)
Swanson et al. (2011) [64]	USA	Prospective cohort study	Adults with inactive CD and UC (n = 14) and HC (n = 7)	1–3 Glasses of red wine daily	1 wk	CAI, FC, intestinal permeability, and CRP level	No difference in CAI or CRP. FC reduced from baseline (P=0.001), intestinal permeability increased in CD or UC

Author (year)	Country	Design	Population	Interventions and sample size	Study duration	Outcomes of interest	Impact on induction of remission/maintenance of remission
Lewis et al. (2021) [109]	USA	RCT	Adults with CD with mild to moderate symptoms	6 wk of prepared meals and snacks SCD (n=101) and MedDiet (n=93), followed by 6 wk of independent adherence to the SCD or MedDiet as recommended by a dietitian via the specific study website	12 wk	Primary outcome was symptomatic remission at 6 wk, and inflammation markers (FC and CRP) response as secondary outcomes	There was significant improvement in symptomatic remission within the SCD and MedDiet groups (P=0.002). However, there insignificant difference in the change between the 2 groups (SCD 46.5%, MedDiet 43.5%; P=0.77). The % of participants that achieved FC (SCD 34.8%, MedDiet 30.8%; P=0.83) and CRP (SCD 5.4%, MedDiet 3.6%; P=0.68) did not differ between the 2 arms
Sigall Boneh et al. (2024) [110]	Israel	Prospective, cross-sectional study	Children and adolescents with CD in clinical remission under biologic therapy	99 Patients assessed on adherence to MedDiet	16 mo	Inflammatory markers (FC)	MedDiet decreased FC levels, OR 0.75 ([95% CI, 0.60–0.95], P=0.019). Vegetable consumption showed inverse relationship with elevated FC
Chiba et al. (2010) [111]	Japan	Single center RCT	Adults with CD in clinical remission	A 1,700-kcal/day semi-vegetarian: a MedDiet-like diet (SVD n = 16) and Omnivorous diet (n = 6)	24 mo	Clinical relapse of CD	15 (94%) of SVD group-maintained remission vs. 2 out of 6 in the Omnivorous diet. SVD showed significant prevention compared to omnivorous (P=0.0003). CRP was normal for all the SVD group at the final visit

Study (year)	Country	Design	Population	Interventions and sample size	Study duration	Outcomes of interest	Impact on induction of remission/maintenance of remission
Erol Doğan et al. (2024) [112]	Turkey	Multicenter RCT	Adults with mild-to-moderate active UC	Control group received MedDiet + biweekly nutrition education on MedDiet (n = 16), the 2nd group had MedDiet+1,600 mg/day of curcumin supplementation (n = 16), and the 3rd group consumed MedDiet+500 mg/day of resveratrol supplementation (n = 16)	8 wk	Disease activity index, serum inflammatory markers, and quality of life	MedDiet, MedDiet+C, and MedDiet+R interventions were effective in reducing disease activity and inflammation and improving quality of life in individuals with UC (P < 0.05). No significant difference was however found between groups in all parameters
Godny et al. (2020) [113]	Israel	Prospective multicenter observational study	Adults with UC after pouch surgery	153 Participants	8 yr follow-up	Disease activity (pouchitis) and inflammatory biomarkers (FC and CRP)	Higher MedDiet scores decreased calprotectin levels (OR = 0.74 [0.56–0.99]). Higher adherence to MedDiet (score ≥ 5) significantly reduced the rates of pouchitis P=0.17)
Haskey et al. (2022) [114]	Canada	Murine model	Muc2-deficient mice with spontaneous colitis	4 Arms groups: the MedDiet fat blend, corn oil, olive oil, and milk fat recipients	9 wk	Disease activity, inflammatory biomarkers and metabolic parameters	MedDiet reduced the clinical and histopathological scores and induced tolerogenic CD103+ CD11b+ dendritic, Th22 and IL-17+ IL-22+. MedDiet was also associated with beneficial microbes
Haskey et al. (2023) [115]	Canada	Single center RCT	Adults with quiescent UC	MDP (n = 15) plus 1 on 1 coaching and CHD (n = 13)	12 wk	Clinical Colitis Activity Index, FC, and fecal microbiome	9 of 12 on CHD had FC > 100 μg/g, vs. 3 of 15 in the MDP group. Higher fecal SCFAs in MDP group (P=0.01). MDP induced changes in protective microbial species

Study (year)	Country	Design	Population	Interventions and sample size	Study duration	Outcomes of interest	Impact on induction of remission/maintenance of remission
Chicco et al. (2021) [116]	Italy	Prospective interventional	Adults with CD (n = 58) or UC (n = 84)	Dietary counselling on adherence MedDiet	6 mo	Anthropometry, DAI, QoL, CRP, FC	Reduction in active disease and improved QoL in both groups; reduced CRP and FC
El Amrousy et al. (2022) [117]	Egypt	Prospective randomized case-controlled	Children with moderately active CD (n = 52) and UC (n = 48)	MedDiet or usual diet	12 wk	Disease activity and inflammatory markers	MedDiet led to higher remission rates and lower inflammatory markers
Strisciuglio et al. (2020) [118]	Italy	Prospective cross-sectional	Children with CD (n = 52) and UC (n = 72) in clinical remission and matched HCs (n = 125)	3-DFD and KIDMED questionnaire	12 wk	FC, MedDiet adherence	Adherence to MedDiet associated with lower FC (P=0.027)