By Ghazaleh Barghgir, MD, and Nancy Selfridge, MD
Dr. Barghgir is a Clinical Skills Facilitator, Clinical Foundations Department, Ross University School of Medicine, Barbados, West Indies.
Dr. Selfridge is Professor, Clinical Foundations Department, Ross University School of Medicine, Barbados, West Indies.
Dr. Barghgir and Dr. Selfridge report no financial relationships relevant to this field of study.
SUMMARY POINTS
• Dietary proinflammatory potential can be identified by an empiric dietary inflammatory pattern score that correlates consumption of distinct food groups with circulating blood markers of inflammation.
• Dietary patterns associated with higher proinflammatory scores included higher consumption of red meat and refined grains and low consumption of dietary fiber.
• A shift from a lower- to a higher-inflammatory diet and a persistently proinflammatory diet both were associated with a significant risk of Crohn’s disease, but not of ulcerative colitis.
SYNOPSIS: An analysis of data from three large prospective cohort studies revealed a proinflammatory diet as a risk factor for incident Crohn’s disease, but not for ulcerative colitis.
SOURCE: Lo C-H, Lochhead P, Khalili H, et al. Dietary inflammatory potential and risk of Crohn’s disease and ulcerative colitis. Gastroenterology 2020;159:873-883.
Ulcerative colitis (UC) and Crohn’s disease (CD) are the most common chronic inflammatory bowel diseases (IBD) worldwide. Patients with these diseases experience decreased quality of life, significant potential for complications, and high rates of hospitalization during symptom flares.
The public health effect of these diseases is profound. In 1999, there were 1.8 million Americans with IBD, increasing to 3.1 million (approximately 1.3% of the U.S. population) by 2015.1 The direct costs of hospitalizations alone were estimated to exceed $6.8 billion in 2008.2
Although the precise pathogenesis of IBD is not completely understood, it is believed that many risk factors play a role, including diet and other environmental factors, immunologic factors, infectious agents, genetic susceptibility, and alterations in the gut microbiome.
Recently, more than 200 genes have been identified that may increase the risk of IBD. However, that would account for only a modest proportion of the disease variance (~13% for CD, ~7% for UC).3 Given that only a small percentage of cases can be linked to genetic factors alone, the substantial increase in the incidence of IBD in the past few decades points to changing environmental factors, primarily diet, as a potential significant risk.
The standard American diet or Western diet pattern, characterized by low consumption of fruits and vegetables and a high consumption of saturated fat, red meat, refined grains, and processed foods, has been shown to be proinflammatory.2
For example, red meat’s role in gut inflammation has been linked to the generation of potentially toxic substances, such as ammonia, amines, and heme, contained in meat products.4 Changes in the gut microbiome, altering the homeostasis of the host, and altering T-cell responses are some of the proposed mechanisms by which diet either can worsen or mitigate intestinal inflammation.5 Thus, given the potential importance of diet in modulating intestinal inflammation, Lo et al investigated associations between dietary proinflammatory potential, as indicated by empirical dietary inflammatory pattern (EDIP) score, and then associated dietary proinflammatory potential with incident ulcerative colitis and Crohn’s disease.
Data was collected from the following three large prospective cohort studies:
- Nurses’ Health Study (NHS), 1984-2014 (121,700 female nurses aged 35-50 years);
- Nurses’ Health Study II (NHS II), 1991-2015 (116,429 female nurses aged 25-42 years); and
- Health Professional Follow-up Study (HPFS) 1986-2012, (51,529 male health professionals aged 40-75 years).
In all three cohorts, questionnaires were completed by participants upon enrollment, and follow-up questionnaires were completed every two years thereafter to gather longitudinal information about various lifestyle factors, medications, and diet. A validated semiquantitative food frequency questionnaire (FFQ) was used to gather dietary information beginning in 1980, 1991, and 1986 in the NHS, NHS II, and HPFS, respectively, and was updated every two to four years.
Lo et al used EDIP scores, previously developed in the NHS study and validated in NHS II and HPFS, as well as the Women’s Health Initiative, to identify associations between consumption patterns of 39 predefined food groups most predictive of elevations of three plasma inflammatory markers: tumor necrosis factor-α receptor 2 (TNF-αR2), interleukin 6 (IL-6), and
C-reactive protein (CRP).6
An EDIP score was determined for subject dietary patterns at each data collection, weight-based on 18 of the 39 food groups. The mean daily intake of each group was first divided by a predetermined portion size, then multiplied by a specific inflammatory coefficient derived for that group based upon its previously demonstrated potential to increase plasma inflammatory markers. The final values were then rescaled by dividing by 1,000 to simplify their interpretation, with higher scores representing proinflammatory diets and lower ones indicating anti-inflammatory diets. Food groups associated with higher and lower EDIP scores are shown in Table 1.6
Table 1. Food Group Associations with EDIP Scores |
|
|
Foods Associated with High EDIP Scores* |
Foods Associated with Low EDIP Scores** |
|
|
|
EDIP: empiric dietary inflammatory pattern * Food groups positively associated with inflammatory marker concentrations **Food groups inversely associated with inflammatory marker concentrations |
|
Permission to review medical records was obtained from any participants ever diagnosed with UC or CD. Two board-certified gastroenterologists, blinded to the study outcome and subject exposure status, independently reviewed medical records and verified disease status using standardized criteria. Participants who had been diagnosed with CD, UC, or cancer (except for nonmelanoma skin cancer) at the start of follow-up, or who reported calorie intakes of < 600 or
> 3,500 kcal/day for women and < 800 or > 4,200 kcal/day for men, were excluded from the study.
Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals (CIs), adjusting for age and multiple potential IBD risk factor variables in the collected data. Those variables included race, smoking status, regular nonsteroidal anti-inflammatory drug use, body mass index (BMI), physical activity, oral contraceptive use, and hormone replacement therapy use. The primary outcome of interest was the risk of developing CD and UC, and the main exposure was the EDIP score, which was expressed as a cumulative average score from baseline. Change in dietary inflammatory potential over time (measured by changes in EDIP score tertile) and subsequent risk of developing IDB also were explored by using participants maintaining the lowest persistent EDIP scores as the reference group.
Ultimately, this study included an analysis of data from 166,903 female and 41,931 male participants, accounting for 4,949,938 person-years of follow-up. CD cases totaled 328, and UC cases totaled 428, with incidence rates of 6.6 and 8.6 per 100,000 person-years, respectively, and with median age/age-range of diagnosis 55 years (range, 29-85 years). Higher EDIP scores were associated with high BMI and lower physical activity, and a dietary pattern of higher red meat and lower dietary fiber intake was shown to be more proinflammatory.
Subjects with the highest quartile of EDIP scores had a 51% significantly higher risk of CD (hazard ratio [HR] of 1.51 [95% CI, 1.10-2.07]) with an incidence of 8.7 per 100,000 person-years, compared to an incidence of 5.8 per 100,000 person-years in the lowest EDIP score quartile.
Results were subsequently adjusted for dietary intake of fiber. No significant differences were found, suggesting that difference in dietary fiber intake alone is unlikely to be responsible for the association (HR for fourth quartile vs. first quartile 1.10 [95% CI, 0.83-1.46]; Ptrend 0.44).
Comparing subjects who maintained the lowest EDIP scores over time to those whose EDIP scores changed from the lowest to the highest tertiles, the latter group experienced a significantly higher incidence of CD (HR 2.05 [95% CI, 1.10-3.79]), amounting to a two-fold increase in incident CD risk. Dietary shift from the highest inflammatory potential to the lowest inflammatory potential over time was associated with risk of CD that was not statistically different than maintaining a low inflammatory diet (HR 1.50 [95% CI, 0.76-2.98]). Of interest, no statistical association between EDIP score and incident ulcerative colitis was noted in any analyses. A summary of these results can be found in Table 2.
Table 2. EDIP Score Trends and the Risk of Crohn’s Disease and Ulcerative Colitis |
||||
|
Eight-Year Change Trend in EDIP* |
Crohn’s Disease |
Ulcerative Colitis |
||
|
Number |
Multivariable-adjusted HR (95% CI) |
Number |
Multivariable-adjusted HR (95% CI) |
|
|
Low-low |
29 |
1 (reference) |
52 |
1 (reference) |
|
Low-moderate |
22 |
1.34 (0.77-2.35) |
29 |
0.99 (0.63-1.57) |
|
Low-high |
16 |
2.02 (1.09-3.75) |
14 |
1.02 (0.56-1.86) |
|
Moderate-low |
16 |
1.13 (0.61-2.10) |
19 |
0.67 (0.39-1.14) |
|
Moderate-moderate |
21 |
1.01 (0.57-1.79) |
29 |
0.80 (0.51-1.28) |
|
Moderate-high |
20 |
1.34 (0.75-2.39) |
19 |
0.73 (0.43-1.24) |
|
High-low |
12 |
1.50 (0.76-2.98) |
11 |
0.72 (0.37-1.39) |
|
High-moderate |
19 |
1.34 (0.74-2.42) |
25 |
1.00 (0.61-1.64) |
|
High-high |
50 |
1.72 (1.07-2.78) |
44 |
0.91 (0.60-1.38) |
|
EDIP: empiric dietary inflammatory pattern; HR: hazard ratio; CI: confidence interval *The eight-year change in EDIP score was calculated by subtracting baseline EDIP score from a follow-up EDIP score determined eight years after baseline. |
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COMMENTARY
This analysis of pooled longitudinal cohort data has several strengths, resulting in significant contributions to previous research exploring dietary patterns and risk of incident IBD. The study’s use of validated FFQs to arrive at EDIP scores allowed for an elegant way of stratifying dietary proinflammatory potential, linked to actual plasma inflammatory markers. The study’s statistical analyses adjusted for multiple IBD risk factor variables in subjects, which helped strengthen confidence in the observed associations between diet patterns and incident IBD.
In multiple studies, dietary fiber intake has been shown to be inversely associated with incident CD; this study showed the association between lower EDIP scores and lower risk of incident CD is not solely because of dietary fiber. Another study strength is the analysis of IBD risk associated with changes in dietary inflammatory potential over time, clearly indicating that changing from a lower inflammatory diet to a higher inflammatory diet increases the statistical risk of incident CD.
Although epidemiologic studies have demonstrated a link between red meat intake (which also would increase dietary inflammatory potential and EDIP score) and UC, this study did not find an association between diet and incident UC. The authors hypothesize that intestinal luminal content involving the microbiome or metabolites may be more relevant in the pathophysiology of CD, and systemic factors involving immunologic or epithelial barrier defects may be more relevant in the development of UC.
The health benefits of including more plant-based food in the standard American diet are heavily supported in research literature. This study data supports an additional dietary recommendation to reduce consumption of proinflammatory food groups, including red meat, foods high in saturated fat, refined grains, and most processed and fast foods.
Patients at risk for CD may be advised that higher intake of these foods is associated with an increased risk for this disease. Since these findings suggest that a proinflammatory diet may trigger intestinal inflammation, advising avoidance of such foods may be helpful for disease management for patients with established IBD while awaiting further research evidence to support this specific management recommendation.
REFERENCES
- Dahlhamer JM, Zammitti EP, Ward BW, et al. Prevalence of inflammatory bowel disease among adults aged ≥ 18 Years — United States, 2015. MMWR Morb Mortal Wkly Rep 2016;65:1166-1169.
- Amre DK, D’Souza S, Morgan K, et al. Imbalances in dietary consumption of fatty acids, vegetables, and fruits are associated with risk for Crohn's disease in children. Am J Gastroenterol 2007;102:2016-2025.
- Jostins L, Ripke S, Weersma RK, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119-124.
- Geypens B, Claus D, Evenepoel P, et al. Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. Gut 1997;41:70-76.
- Manzel A, Muller DN, Hafler DA, et al. Role of “Western diet” in inflammatory autoimmune diseases. Curr Allergy Asthma Rep 2014;14:404.
- Tabung FK, Smith-Warner SA, Chavarro JE, et al. An empirical dietary inflammatory pattern score enhances prediction of circulating inflammatory biomarkers in adults. J Nutr 2017;147:1567-1577.
An analysis of data from three large prospective cohort studies revealed a proinflammatory diet as a risk factor for incident Crohn’s disease, but not for ulcerative colitis.
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