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REVIEW ARTICLE

Effect of Lifestyle Factors on Outcomes in Patients With Inflammatory Bowel Diseases

Rozich, Jacob J. MD1; Holmer, Ariela MD2; Singh, Siddharth MD, MS2,3

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The American Journal of Gastroenterology: June 2020 - Volume 115 - Issue 6 - p 832-840
doi: 10.14309/ajg.0000000000000608
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Abstract

The global incidence and prevalence of inflammatory bowel diseases (IBDs) is rising, with a steep increase in incidence in newly industrialized countries (1). Various lifestyle factors besides diet including physical activity (and obesity) and smoking have been implicated in the recent epidemiological trends in the risk of developing IBD and have been covered elsewhere (2,3). This review focuses on how important lifestyle factors—physical activity (and obesity), smoking, alcohol consumption and cannabis use, sleep, and stress—affect the natural history and outcomes in patients with established IBD, and how modifying lifestyle may improve IBD outcomes. The impact of diet and dietary modification in patients with established IBD has been covered elsewhere.

PHYSICAL ACTIVITY AND OBESITY IN PATIENTS WITH IBD

Physical activity and exercise may be associated with a decreased risk of developing IBD, particularly Crohn's disease (CD). However, the development of IBD, particularly presence of active symptoms, impairs patients' ability to exercise and participation in sports activities (4,5). In survey studies, approximately 50% patients report that IBD moderately or significantly impacted their fitness (4). One of the consequences of lack of exercise is obesity. Approximately 15%–40% adult patients with IBD are obese (body mass index [BMI] ≥30 kg/m2), and an additional 20%–40% are overweight, with a comparable distribution of obesity in CD and ulcerative colitis (UC) (6).

Impact of physical activity and obesity on the natural history of IBD

Physiologically, the benefits of exercise in boosting immune response and reducing proinflammatory cytokines are well known (7). Voluntary exercise in animal models of chemical-induced colitis has also shown to mitigate symptoms and reduce inflammatory burden (8). However, there have been limited studies on the impact of physical activity and exercise on the natural history of IBD. Most cross-sectional studies have focused on how IBD disease activity may negatively impact ability to exercise and are confounded by disease severity. In a prospective cohort study of 1857 patients with IBD, Jones et al. (9) observed that a higher level of exercise was independently associated with 24%–32% lower risk of symptomatic relapse over 6 months among patients in remission.

Obesity, in contrast, has been associated with a lower prevalence of clinical remission and higher anxiety, depression, fatigue, pain, and inferior social function scores on PROMIS measures compared with nonobese patients with IBD (10). Longitudinal studies suggest that obesity may negatively impact clinical course and health care utilization (Table 1). In a large internet-based cohort study of 7,296 patients with IBD (4,748 patients with CD, 19.5% obese; 2,548 patients with UC, 20.3% obese), Jain et al. (10) observed that obesity was independently associated with an increased risk of persistent disease activity or relapse in patients with CD (class II or III obesity vs normal BMI: odds ratio [OR], 1.86; 95% confidence interval [CI], 1.30–2.68) and UC (OR, 2.97; 95% CI, 1.75–5.17), with a dose-response relationship. In a propensity score–matched, nationally representative cohort study of 42,285 patients with IBD (12.4% obese), Nguyen et al. (11) observed that obese patients with IBD had a higher annual burden and costs of hospitalization compared with nonobese patients. Besides overall obesity, visceral adiposity has been more consistently associated with adverse outcomes in patients with IBD. High visceral adipose tissue volume was associated with an increased risk of penetrating or stricturing complications (OR, 1.7; 95% CI, 1.1–2.9), hospitalization (OR, 1.9; 95% CI, 1.2–3.4), and shorter time interval to surgery (HR, 1.4; 95% CI, 1.0–2.0), after adjusting for age and BMI in a pediatric cohort of patients with CD (12). High visceral fat area has also been associated with an increased risk of recurrence of CD after surgical resection (13).

Table 1-a
Table 1-a:
Key longitudinal studies on the impact of obesity on disease course and complications in patients with inflammatory bowel diseases
Table 1-b
Table 1-b:
Key longitudinal studies on the impact of obesity on disease course and complications in patients with inflammatory bowel diseases

Impact of physical activity and obesity on treatment response and surgery in IBD

There have been limited studies on how usual physical activity may modify pharmacologic treatment response in patients with IBD. Biologically, exercise has been shown to reduce tumor necrosis factor-α (TNFα), which may conceivably augment response to TNFα antagonists, although this has not been studied (14). Physical fitness is associated with superior outcomes after major surgery, including abdominal surgery. Several randomized trials and meta-analyses have also demonstrated the benefit of physical exercise prehabilitation, including aerobic exercises and/or resistance training in reducing postoperative morbidity and pulmonary complications in patients undergoing major abdominal surgery (15,16).

In contrast, population pharmacokinetic studies of all biologic agents used in IBD have identified high body weight as a risk factor associated with increased drug clearance, resulting in shorter half-lives and low trough drug concentrations (6). This effect might be related to impaired absorption of subcutaneously administered agents, rapid proteolysis, and to a TNF-sink phenomenon with higher inflammatory burden due to adipose tissue in obese patients. Kurnool et al. (17) observed that each 1 kg/m2 increase in BMI was associated with 4% increase in the risk of treatment failure, 8% increase in the risk of surgery or hospitalization, and 6% lower odds of achieving endoscopic remission in a cohort 160 biologic-treated patients with UC, with comparable effects seen with fixed-dose therapies and weight-based agents. In a prospective cohort of adalimumab-treated patients with CD, Bultman et al. (18) observed that over one-third of patients were dose escalated to weekly adalimumab within a median 5 months of initiating therapy, and BMI was the only independent predictor of dose escalation. However, a post hoc analyses of clinical trials of infliximab in IBD demonstrated no association between obesity and short-term clinical remission and mucosal healing in infliximab- or placebo-treated patients (19,20). In a systematic review of 54 cohorts including 19,372 TNFα antagonist-treated patients with immune-mediated inflammatory diseases (23% obese), Singh et al. (19) observed that patients with obesity had 60% higher odds of failing therapy (OR, 1.60; 95% CI, 1.39–1.83), with a dose-response relationship; each 1 kg/m2 increase in BMI was associated with 6.5% higher odds of treatment failure. Whether a similar negative effect of obesity on response to targeted small molecule inhibitors, such as tofacitinib exists, is unclear.

Intra-abdominal surgeries in patients with obesity are both technically challenging and are associated with higher rates of postoperative complications than surgeries in patients with a normal BMI. In a systematic review, Makino et al. (21) observed longer operative times, an increased likelihood of conversion to open procedures, more comorbidities, a higher risk of postoperative complications (in particular wound infection), and a longer length of hospital stay in obese patients undergoing colorectal resection compared with individuals who were not obese. Two aspects of surgery that might be particularly challenging in patients with IBD merit special mention. First, obesity makes creating a stoma challenging due to stomal retraction, higher rates of complications such as parastomal hernia, mucocutaneous separation, and stoma prolapse. Second, the mesentery of patients with obesity tends to be foreshortened by the mesenteric fat, making it more challenging to create a J-pouch in patients with UC. Obesity increases the risk of short-term postoperative complications in patients undergoing ileal pouch–anal anastomosis, although long-term outcomes might be comparable to those in patients without obesity in experienced centers (22).

Can structured exercise interventions and treating obesity help IBD?

Several small studies have evaluated the impact of diverse structured exercise interventions, including cardiovascular training, strength training, yoga, and mind-body therapies, on outcomes in patients with IBD, albeit or poor methodological quality and short duration of follow-up (14). These studies have generally demonstrated improvement in overall fitness, increase bone mineral density, and reduction in stress and anxiety. However, they have variably demonstrated modest benefits in IBD-related clinical disease activity or biochemical markers of inflammation. Experts have recommended maintaining an active lifestyle with moderate-intensity endurance and resistance exercise in an enjoyable activity at least 30 minutes per day, 3 times per week in patients with mild to moderately active IBD (14).

Although there are no interventional studies of intentional weight loss in IBD, trials of diet and/or lifestyle-induced weight loss in other autoimmune diseases suggest improvement in disease outcomes with weight loss. In trials in obese patients with psoriasis, those randomized to weight loss intervention were 2.9 times more likely to achieve remission compared with those without intervention (OR, 2.92; 95% CI, 1.39–6.13) (23). In a randomized trial comparing low calorie or free-managed diet in 126 patients with psoriatic arthritis starting anti-TNF therapy, Di Munno et al. (24) observed that regardless of type of intervention, patients who achieved ≥5% weight loss were 4.2 times more likely to achieve clinical remission compared with those who experienced <5% weight loss. Similar benefits with weight loss in obese patients with IBD are conceivable. Case series have shown that bariatric procedures in selected morbidly obese patients with IBD result in improvement in disease activity after weight loss (25). Diet and lifestyle modifications to achieve weight loss may be challenging in patients with IBD due to active gastrointestinal symptoms and a high prevalence of comorbid irritable bowel syndrome. Endoscopic bariatric interventions are currently contraindicated in patients with IBD; pharmacological weight loss interventions are attractive. A phase 2 clinical trial of an Food and Drug Administration-approved weight loss medication, phentermine-topiramate in obese biologic-treated patients with UC is ongoing.

SLEEP AND SLEEP DISTURBANCE IN PATIENTS WITH IBD

Sleep disturbance is prevalent in patients with IBD. Between 47% and 82% of patients with IBD report disrupted sleep, night-time awakenings, and nonrestorative sleep compared with one-third of the general population (26,27). In a large study of 3,173 patients with IBD, 60% reported sleep disturbance at baseline (28). Strongest risk factors for sleep disturbance were depressive symptoms and active disease, with female sex, smoking, and diagnosis of CD (vs UC) also being associated with sleep disturbance. The relationship between sleep, sleep disturbance, and IBD is bidirectional. Active disease is invariably associated with poor sleep quality. In a prospective study, all patients with symptomatically active IBD had poor sleep quality compared with 73% of patients with quiescent disease (27). This includes more awakenings, longer sleep latency, and reduced stage 3 sleep using electroencephalographic recordings compared with patients with quiescent disease and healthy controls. Even among patients with quiescent disease, patients with IBD have inferior sleep quality compared with healthy controls, similar to patients with irritable bowel syndrome, with prolonged sleep latency, greater sleep fragmentation, shorter sleep duration, and greater use of sleep aids. Rates of sleep disturbance are higher in patients with objective evidence of inflammation, independent of symptoms (29).

Circadian misalignment in patients with IBD

Circadian homeostasis maintains the sleep-wake cycle and plays a key role in preserving healthy immune function (30). Disruption of this process, or circadian misalignment, can promote inflammatory diseases such as IBD. Contributors to circadian misalignment include social jet lag (discrepancy between innate circadian rhythms and actual sleep time due to social obligations), sleep debt (difference between the average sleep duration during the work week and work-free days), and chronotype (a person's biological inclination to sleep during a certain time of day). Cross-sectional studies have demonstrated that compared with healthy controls, patients with IBD have higher social jet lag and sleep debt (31). Moreover, this circadian misalignment has been associated with more aggressive CD with stricturing and fistulizing behavior and CD-related surgery.

Impact of sleep disturbance on the natural history and outcomes in IBD

Prospective cohort studies have demonstrated the negative impact of sleep disturbance on risk of relapse and impaired quality of life in patients with IBD. In a cohort study, Ananthakrishnan et al. (28) observed that sleep disturbance was independently associated with 1.6- to 2-fold higher risk of disease flare over 6 m in 651 patients with CD in clinical remission at baseline. In contrast, they did not observe any significant association between sleep disturbance and subsequent risk of relapse in patients with asymptomatic UC. Poor sleep quality is also a significant contributor to fatigue observed in patients with IBD. In a prospective, population-based Manitoba IBD cohort study, fatigue was a common symptom reported in 72% patients with active disease and 30% patients with inactive disease (26). In these patients, poor sleep quality was independently associated with fatigue in both patients with active and inactive IBD. Similarly, Borren et al. (32) observed that sleep disruption in patients with inactive IBD is associated with persistent fatigue. A positive feedback loop might exist whereby active disease leads to poor sleep that in turn worsens inflammation, with both factors leading to fatigue.

Can improving sleep hygiene improve outcomes in patients with IBD?

Treating active IBD with pharmacotherapy has been associated with improved sleep hygiene in patients with IBD. However, it remains unclear how improving sleep hygiene impacts outcomes in patients with IBD. No clinical trials have evaluated whether structured interventions to improve sleep quality decrease the risk of clinical relapse and improve objective measures of inflammation in patients with IBD. However, it is conceivable that the improving sleep hygiene would improve fatigue and quality of life in patients with IBD. Experts recommend systematic evaluation of sleep hygiene in patients with IBD with fatigue (33,34). Patients with poor sleep quality should be screened for comorbid conditions such as obstructive sleep apnea, restless legs syndrome, and insomnia and educated on sleep hygiene. Patients with persistent sleep disturbance should be referred to a sleep specialist for potential pharmacotherapy and behavioral therapy.

STRESS IN PATIENTS WITH IBD

In contrast to psychiatric illnesses such as depression and anxiety, stress is broadly defined as threat to a steady state of homeostasis in an individual's life and implicates both a stressor (i.e., an environmental demand) and an individual's physiological and emotional response to the stressor (35). Stress is pervasive in modern lifestyle with approximately 60% of Americans reporting stress. Exaggerated response to a stressor may be functionally disruptive and evolve into a psychiatric illness; conversely, in a patient with anxiety, stress perception may be disproportionate to environmental demand. Although the negative impact of major psychological comorbidities on disease activity and health care utilization in patients with IBD is increasingly being recognized, the impact of daily stressors and perceived stress on disease course and outcomes in patients with IBD is less clear (36). Pathophysiologically, stress has been demonstrated to negatively impact gastrointestinal function and increase gut permeability through its impact on the immune, endocrine, and nervous system.

Impact of stress on the natural history and outcomes in patients with IBD

Patients with chronic health conditions, such as IBD, have a higher prevalence of stress than the general population in common domains of finances, work, and family. Stress, particularly perceived stress, can impact IBD disease activity. Early retrospective case-control studies have variably suggested that major stressful life events may lead to a higher risk of developing IBD, although they were limited by recall bias (37,38). More importantly, measuring stress based only on occurrence of life events captures burden of conventional stressors and not an individual's response to it, often referred to as perceived stress. Prospective cohort studies have suggested that high perceived stress in the preceding 3–6 months may be associated with an increased risk of symptomatic flares (39–42). In a survey study of 600 patients in the population-based University of Manitoba IBD Research Registry, high perceived stress in the preceding 3 months, as measured by the Cohen's Perceived Stress Scale, and not the occurrence of a major life event or negative mood, was associated with 2.4-fold higher odds of developing a flare, based on clinical disease activity indexes (39). However, perceived stress was not associated with increased fecal calprotectin, as a biomarker of inflammation, suggesting that the impact of stress may be mediated through its impact of gastrointestinal function and not necessarily an abnormal immune response (43). In a comprehensive prospective cohort study evaluating clinical, biological, and psychosocial parameters predictive of clinical relapse in 101 patients with quiescent CD, Bitton et al. (44) observed that besides conventional factors of high-risk phenotype (elevated C-reactive protein, presence of fistulizing disease), patients with high perceived stress and ineffective avoidance coping had a shorter time to relapse. Besides the impact of an acutely stressful event, chronically high perceived stress is independently associated with a higher risk of relapse. In a prospective cohort study of 62 patients with UC followed over 5 years, Levenstein et al. (45) observed that high long-term (>2 years) perceived stress tripled the risk of UC flare.

The relationship between stress and IBD symptoms is bidirectional. Approximately 30% patients with symptomatic IBD report higher rates of perceived stress due to their IBD; in contrast, patients with IBD who are asymptomatic are significantly less likely to report stress due to their IBD (46).

Can decreasing stress improve outcomes in patients with IBD?

Stress management is challenging, with the pervasive nature and diverse settings and sources of stress. RCTs of psychological therapy including cognitive behavioral therapy, mindfulness-based therapies such as meditation and yoga, and gut-directed hypnotherapy have not been shown to be effective in decreasing perceived stress in patients with IBD (47). Although these therapies may improve quality of life and depression over a short term, they have not been shown to significantly improve disease activity or decrease the risk of clinical relapse.

SMOKING IN PATIENTS WITH IBD

Cigarette smoking has been associated with an increased risk of developing CD, particularly in Western countries, although with a lower risk of developing UC across all regions (2). Continued smoking, smoking cessation, and nicotine replacement may variably modify outcomes in patients with established IBD.

Impact of smoking on outcomes in IBD

CD.

Smoking has consistently been associated with a more severe phenotype, complicated behavior, and adverse outcomes in CD (48–50). In a recent Spanish registry–based cohort of 3,224 patients with CD, current smokers were more likely to have ileum-dominant CD, perianal disease, and stricturing phenotype. Smoking has also been associated with progression from inflammatory to penetrating or stricturing behavior (51). In a meta-analysis of 33 high-quality cohort studies with ∼11,000 patients with CD, To et al. (52) observed that compared with nonsmokers, smokers had 56%–85% increase CD flares, a nearly twofold increase in clinical recurrence after surgery, a 54%–68% increase in the need for first surgery, and a twofold increase in rates of second surgery. Smoking has been associated with higher corticosteroid use, corticosteroid-requiring disease flares, and corticosteroid dependency (53). Smokers also achieve higher 6-thioguanine nucleotide levels compared with nonsmokers, although it has not been consistently associated with higher effectiveness of thiopurines (54,55). In the TOPPIC trial comparing mercaptopurine vs placebo for preventing recurrence of CD after surgery, mercaptopurine was effective in decreasing the risk of clinical recurrence only in patients who were smokers; no benefit was observed in nonsmokers (56). However, smoking has not been shown to modify response to biologic therapy (57,58).

UC.

Unlike CD, smoking does not negatively impact clinical outcomes in patients with established UC and may potentially be protective against adverse outcomes. In a nationally representative study of 6,754 patients with UC (13% smokers at diagnosis), Blackwell et al. (59) observed no significant difference in the risk of severe UC flare requiring corticosteroids, corticosteroid dependency, and need for thiopurines between smokers, ex-smokers, and nonsmokers. In a meta-analysis of 16 high-quality cohort studies, there was no significant difference in the risk of UC flare (smokers vs nonsmokers: 4 studies; OR, 1.26; 95% CI, 0.65–2.44), colectomy (5 studies; OR, 0.89; 95% CI, 0.62–1.26), proximal disease extension (4 studies; OR, 0.57; 95% CI, 0.20–1.66), and development of pouchitis in patients with ileal pouch anal anastomosis (3 studies; OR, 0.57; 95% CI, 0.21–1.53) (60). In contrast, in a 2015 meta-analysis of 20 observational studies in patients with UC, including case-control studies, smokers had a lower risk of colectomy compared with nonsmokers (OR, 0.55; 95% CI, 0.33–0.91) (61).

Impact of smoking cessation on outcomes in IBD

CD.

Smoking cessation seems to mitigate risk and adverse outcomes associated with smoking in patients with CD. In a prospective cohort study of 899 patients with CD (474 nonsmokers, 59 quitters) followed over 29 months, Cosnes et al. (62) observed that the risk of disease flare, corticosteroid exposure, and treatment modification was comparable between quitters and never smokers and was significantly lower compared with continued smokers. In another population-based inception cohort study of 749 patients with CD who were smokers at diagnosis, 44% quit within 2 years of CD diagnosis (53). Compared with persistent smokers, those who quit smoking were less likely to be corticosteroid dependent on follow-up, although rates of intestinal resection were not different. Meta-analyses have also suggested no significant differences in former vs never smokers in risks of disease flare, initial and repeat surgery in patients with CD (52).

Despite evidence on the detrimental effects of smoking, and beneficial effects of smoking cessation in patients with CD, smoking prevalence remains high, with many patients being unaware of the detrimental effects of smoking on CD course and outcomes (63). Although passive education on smoking cessation may not be helpful, structured smoking cessation programs involving individual counseling, nicotine replacement, and/or pharmacotherapy have been effective in helping patients with CD quit and may improve disease outcomes (64).

UC.

Anecdotally, patients have associated quitting smoking with triggering a flare of UC, although it has been challenging to establish a true temporal relationship in robust clinical studies. In a case-control study of 32 patients with UC who quit smoking after diagnosis, matched with nonsmoker and continuing smoker controls, Beaugerie et al. (65) observed that patients who quit smoking were more likely to have active disease, be hospitalized, and require treatment with steroids and immunomodulators. More recent systematic studies have failed to demonstrate the negative impact of quitting smoking in patients with UC. In a UK population–based cohort, there was no significant difference in rates of flares requiring corticosteroids, corticosteroid dependence, UC-related hospitalization, or colectomy between patients who quit smoking within 2 years of UC diagnosis vs persistent smokers, although crude rates of corticosteroid use and thiopurine use were higher in those who quit smoking (59). In a meta-analysis, To et al. (60) found no significant difference in the risk of colectomy between ex-smokers, current smokers, and never smokers.

Impact of nicotine replacement in UC

With the protective association between smoking and risk of UC, nicotine replacement therapy has been studied as adjunctive therapy in patients with UC. Early clinical trials of high-dose transdermal nicotine (>15 mg/d) in nonsmoking patients with mild to moderately active UC despite mesalamine therapy suggested benefit in inducing clinical remission, but not in maintaining remission, over placebo (66,67); however, it was not as effective as low-dose prednisone (68). Nicotine enemas, 6 mg/d, were not effective in inducing remission in patients with distal UC (69). Treatment-limiting side effects are common with nicotine, which leads to withdrawal of therapy, and hence, it is not recommended for routine management (70). Its role in modern management of UC, with availability of multiple immunosuppressive therapies, has not been evaluated.

ALCOHOL AND CANNABIS USE IN PATIENTS WITH IBD

Alcohol use in IBD

Alcohol has not been linked definitively as either a risk factor for development of IBD (71,72) or to any specific adverse outcomes (73,74). Two separate meta-analyses, one each for CD and UC, found no association between alcohol consumption and risk of developing CD (6 studies; OR, 0.85; 95% CI, 0.68–1.08) or UC (9 studies; OR, 0.95; 95% CI, 0.65–1.39) (72,75). However, 30–60% of patients with IBD often voluntarily avoid alcohol (76,77). Survey studies have variably suggested either subjective worsening of gastrointestinal symptoms or no change in clinical disease activity or biomarkers of inflammation with alcohol consumption (76,78). Magee et al. (79) observed that dietary intake of wine and beer, but not spirits, in patients with UC across disease spectrum is significantly associated with worse endoscopic disease activity. In a prospective cohort study of 183 patients with UC in remission, Jowett et al. (80) observed that higher intake of alcoholic beverages, particularly sulfite-containing beverages, was associated with a 2.4-fold higher risk of clinical relapse. However, these findings have been inconsistent. In an experimental study in 23 patients with IBD in remission, moderate intake of alcohol (1–3 glasses for red wine per day for 1 week) was not associated with clinical relapse and, in fact, was associated with a significant decline in fecal calprotectin (81). Overall, it seems that moderate alcohol consumption may be safe in patients with IBD.

Cannabis use in IBD

Approximately 10%–20% patients with IBD are active cannabis users, although this is probably underestimated with increasing legalization across North America (82). In survey studies, chronic abdominal pain and prior abdominal surgery were associated with 3.5- to 5-fold higher odds of marijuana use, with self-reported improvement in pain, cramping and diarrhea, and increased appetite, with marijuana (83,84).

Small interventional studies have suggested that cannabis use may improve IBD-related symptoms in patients with CD. In the first RCT of cannabis in 21 patients with active CD, Naftali et al. (85) demonstrated that compared with placebo, smoking 2 cannabis cigarettes per day for 8 weeks was associated with significantly higher rates of clinical response (decline in CD activity index by 100 points) (90% vs 40%, P = 0.03) and numerically higher rates of clinical remission (CD activity index <150; 40% vs 10%, P = 0.11); however, cannabis use was not associated with any significant change in biochemical markers of inflammation. A subsequent RCT of low-dose oral cannabidiol (CBD) of 19 patients with active CD from the same group of investigators failed to demonstrate any positive effect in clinical and biochemical parameters (86). In a placebo-controlled trial in patients with active UC on mesalamine, Irving et al. (87) assessed the efficacy, safety, and tolerability of once-daily oral CBD for 10 weeks. They observed no significant difference in rates of clinical remission (CBD vs placebo: 28% vs 26%), although there were considerable protocol deviations, with 90% patients receiving CBD extract reporting treatment-related adverse events. In contrast, Naftali et al. observed that smoking 2 cannabis cigarettes per day for 8 weeks was associated with clinical and endoscopic response, but no biochemical response, in an RCT of 28 patients with moderate to severely active UC. Although there is considerable enthusiasm for the potential benefit of cannabis, particularly in the patient community, long-term effect of cannabis in these patients with IBD is unknown. In the general population, long-term use of cannabis is associated with an increased risk of addiction to other substances, diminished life achievement, an increase in motor vehicle accidents, symptoms of chronic bronchitis, abnormal brain development in a younger population, psychiatric disturbances, depression, and anxiety, and risk of cannabis hyperemesis syndrome in frequent cannabis users (88). At this point, there is very limited evidence to inform the routine use of cannabis in patients with IBD.

In summary, several modifiable lifestyle factors play a vital role in the course and outcomes of patients with IBD. Figure 1 summarizes key findings on the impact of these lifestyle factors in patients with established IBD. Well-designed prospective cohort studies to better understand their impact on the natural history and randomized interventional studies of lifestyle factor modification are warranted to augment the effectiveness of current pharmacological therapies. In the meantime, a conscious and deliberate assessment of these lifestyle factors is warranted for every patient with IBD and serves as a key aspect in engaging patients in adjunctive self-management of their disease.

Figure 1
Figure 1:
Effect of lifestyle factors on the course of inflammatory bowel diseases. CD, Crohn's disease; IBD, inflammatory bowel disease; UC, ulcerative colitis.

CONFLICTS OF INTEREST

Guarantor of the article: Siddharth Singh, MD, MS.

Specific author contributions: S.S.: study concept and design. J.J.R., A.H., and S.S.: acquisition, analysis, and interpretation of data. J.J.R., A.H., and S.S.: drafting and critical revision of the manuscript. J.J.R., A.H., and S.S.: approval of the final manuscript.

Financial support: S.S. is supported by NIH/NIDDK (K23DK117058), ACG Junior Faculty Development Award, the Crohn's and Colitis Foundation Career Development Award (#404614), Litwin IBD Pioneers Grant (#623346), and AGA-Pfizer Young Investigator Pilot Research Award in Inflammatory Bowel Disease.

Potential competing interests: J.J.R. and A.H.: none to declare. S.S.: research grants from AbbVie and consulting fees from AbbVie, Takeda, and Pfizer.

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