September 2012

Document Type


Degree Name



Dept. of Public Health and Preventive Medicine


Oregon Health & Science University


Background: In the United States about half a million people develop peptic ulcer each year, and the health care costs of this disease amounts to an estimated value of $10 billion annually. To date, there have been no studies evaluating the association between folic acid consumption or folic acid levels, and reduction in peptic ulcers. It might be possible that the mechanism of action of folic acid on amino acid and DNA synthesis might help cells regenerate and act protectively against peptic ulcers. Objective: To evaluate the association between the level of red blood cell folic acid and a history of peptic ulcers using the National Health and Nutrition Examination Survey (NHANES)database from the years 1999-2000. Method: The data for this study were from the NHANES 1999-2000 online public use database. All statistical analyses accounted the complex sample survey design of the NHANES sampling weights. For data analysis we used pearson’s chi-square for categorical variables and t-test for continuous variables. Confounders were selected and added one at a time to the model. Those that changed the association between RBC folic acid and lifetime peptic ulcers by 10% or more were considered as confounders. We also conducted a weighted Wald test for interactions between folic acid and gender, and folic acid and H.pylori. Our outcome variable was defined as peptic ulcer within a lifetime in the (1)/(0) format, while our main exposure was defined as RBC folic acid level. For this purpose we considered a multivariate logistic regression model analysis with a cutoff for confounder inclusion of p < 0.25. The confounder variables considered necessary after their evaluation for possible inclusion in the final multivariate logistic regression model were gender, marital status, ethnicity, age, level of education, smoking exposure, stomach or intestinal illness, income, and veteran or military status. All data analyses were conducted using STATA 11. Results: The association between RBC folic acid levels and a lifetime of peptic ulcers was not statistically significant in either univariate or multivariate logistic regression analyses. Our model showed that as compared to the baseline range of 0ng/ml to 227ng/ml, the odds of ever having a lifetime peptic ulcers remain mostly the same at the 228ng/ml to 301ng/ml range (OR=1.00; 95% CI: 0.54-1.87; p=0.98), the odds of developing a lifetime peptic ulcers decreases at the 302ng/ml to 628ng/ml range (OR=0.79; 95% CI: 0.40-1.58; p=0.48), and the odds of ever having a lifetime peptic ulcers also decreases above 629ng/ml (OR=0.82; 95% CI: 0.44-1.55;p=0.53). However, this dose response effect of decreasing odds of lifetime peptic ulcers with increasing RBC folic acid was not statistically significant (p= 0.393; trend test). Discussion: This study failed to find a significant association between RBC folic acid levels and lifetime peptic ulcers. The data suggests a decrease in lifetime peptic ulcers, as the blood levels of RBC folic acid increase; however, this trend is not supported through statistical significance. Although this is the first study evaluating this association, additional studies are needed to determine a true association between blood levels of RBC folic acid and a reduction in peptic ulcers. Patients, providers, and researchers will benefit from the information produced by this study. Conclusions: Statistically, it is difficult to determine that a dose response association truly exists between RBC folic acid levels and lifetime peptic ulcers. Further studies might validate the dose response trend found in this study. It is biologically possible that an association exists because folic acid helps with the synthesis of DNA and amino acids. Therefore, it is plausible to think that folic acid helps restore cells affected through ulcerations in the gastrointestinal tract, thus decreasing the likelihood of peptic ulcers.




School of Medicine



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