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Long term gluten consumption in adults without celiac disease and risk of coronary heart disease prospective cohort study. Abstract. Objective To examine the association of long term intake of gluten with the development of incident coronary heart disease. Design Prospective cohort study. Setting and participants 6. Nurses Health Study and 4. Health Professionals Follow up Study without a history of coronary heart disease who completed a 1. Exposure Consumption of gluten, estimated from food frequency questionnaires. Main outcome measure Development of coronary heart disease fatal or non fatal myocardial infarction. Results During 2. Compared with participants in the lowest fifth of gluten intake, who had a coronary heart disease incidence rate of 3. After adjustment for known risk factors, participants in the highest fifth of estimated gluten intake had a multivariable hazard ratio for coronary heart disease of 0. P for trend0. 2. After additional adjustment for intake of whole grains leaving the remaining variance of gluten corresponding to refined grains, the multivariate hazard ratio was 1. P for trend0. 7. In contrast, after additional adjustment for intake of refined grains leaving the variance of gluten intake correlating with whole grain intake, estimated gluten consumption was associated with a lower risk of coronary heart disease multivariate hazard ratio 0. P for trend0. 0. Conclusion Long term dietary intake of gluten was not associated with risk of coronary heart disease. However, the avoidance of gluten may result in reduced consumption of beneficial whole grains, which may affect cardiovascular risk. The promotion of gluten free diets among people without celiac disease should not be encouraged. Introduction. Gluten, a storage protein in wheat, rye, and barley, triggers inflammation and intestinal damage in people with celiac disease. People with intestinal or extra intestinal symptoms triggered by gluten but who do not meet formal criteria for celiac disease may have non celiac gluten sensitivity, a clinical entity with an as yet uncharacterized biological basis. Celiac disease, which is present in 0. US population,3 is associated with an increased risk of coronary heart disease, which is reduced after treatment with a gluten free diet. On the basis of evidence that gluten may promote inflammation in the absence of celiac disease or non celiac gluten sensitivity,5 concern has arisen in the medical community and lay public that gluten may increase the risk of obesity, metabolic syndrome, neuropsychiatric symptoms, and cardiovascular risk among healthy people. As a result, diets that limit gluten intake have gained popularity. In an analysis of the National Health and Nutrition Examination Survey NHANES, most people adhering to a gluten free diet did have a diagnosis of celiac disease. Moreover, in a follow up analysis of NHANES, adoption of a gluten free diet by people without celiac disease rose more than threefold from 2. Short of strict gluten avoidance, people may reduce gluten in their diet owing to beliefs that this practice carries general health benefits. The reasons for gluten reduction likely relate to the perception that gluten carries adverse health effects. One national survey showed a steep rise in interest in this diet in recent years, and by 2. US reported that they were trying to minimize or avoid gluten. Concerns exist that a gluten free or gluten restricted diet may be nutritionally suboptimal,1. Despite the rising trend in gluten restriction, no long term, prospective studies have assessed the relation of dietary gluten with the risk of chronic conditions such as coronary heart disease in people without celiac disease. Thus, using prospective, validated data on dietary intake collected over 2. Methods. Study population. The Nurses Health Study NHS is a prospective cohort of 1. US states who were enrolled in 1. The Health Professionals Follow up Study HPFS is a prospective cohort of 5. Participants in NHS and HPFS have been followed via biennial self administered questionnaires on health and lifestyle habits, anthropometrics, environmental exposures, and medical conditions. In 1. 98. 6, diet in both cohorts was assessed with a validated 1. Among the 7. 3 6. NHS and 4. 9 9. 34 men in HPFS who completed a food frequency questionnaire in 1. NHS 4. 8 HPFS 3. NHS 4. 01. 5 HPFS 2. NHS 4. 68. 9 HPFS 1. Participants were specifically asked about a history of celiac disease in 2. NHS 2. 00 HPFS 1. After these exclusions, 6. Return of the mailed questionnaire was considered to imply informed consent. Measurement of exposure and outcome. In both cohorts, diet was assessed in 1. For each food item, participants were asked about the frequency with which they consumed a commonly used portion size for each food over the previous year available responses ranged from never or less than once a month to six or more times a day. We calculated nutrients by using the Harvard T. H. Chan School of Public Health nutrient database, which was updated every two to four years during the period of food frequency questionnaire distribution. We used year specific nutrient tables for ingredient level foods. Previous validation studies have shown that the derivation of nutrient values correlates highly with nutrient intake as measured by one week food diaries in women and men. For each of these two cohorts, we derived the quantity of gluten consumed. We calculated the quantity of gluten on the basis of the protein content of wheat, rye, and barley based on recipe ingredient lists from product labels provided by manufacturers or cookbooks in the case of home prepared items. Previous studies have used conversion factors of 7. Although glutens proportion of total protein may be more variable for rye and barley than for wheat,2. Although trace amounts of gluten can be present in oats and in condiments for example, soy sauce, we did not calculate gluten on the basis of these items as the quantity of gluten is much lower than that in cereals and grains and the contribution to total gluten intake would be negligible. In 1. 98. 6 the five largest contributors to gluten in both cohorts were dark bread, pasta, cold cereal, white bread, and pizza supplementary table A. Previous validation studies within these cohorts found that the Pearson correlation coefficients between the number of servings of these items reported on food frequency questionnaires and that reported on seven day dietary records ranged from 0. A separate validation study of this food frequency questionnaire found that this method of measuring vegetable that is, plant based protein intake, of which gluten is the major contributor, correlated highly with that measured in seven day dietary records Spearman correlation coefficient 0. We divided cohort participants into fifths of estimated gluten consumption, according to energy adjusted grams of gluten per day. We obtained energy adjusted values by regression using the residual method, as described previously. To quantify long term dietary habits, we used cumulative averages through the questionnaires preceding the diagnosis of coronary heart disease, death, or the end of follow up. For example, we calculated cumulative average estimated gluten intake in 1. We treated cumulative average estimated gluten intake as a time varying covariate. For participants with missing dietary data, we used the most recent previous dietary response on record.