Term of Award

Summer 2021

Degree Name

Doctor of Public Health in Epidemiology (Dr.P.H.)

Document Type and Release Option

Dissertation (restricted to Georgia Southern)

Copyright Statement / License for Reuse

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


Department of Biostatistics, Epidemiology, and Environmental Health Sciences

Committee Chair

Jian Zhang

Committee Member 1

Logan Cowan

Committee Member 2

Lili Yu


Background: A shift towards high folate concentrations has emerged following the mandatory folic acid fortification. However, the association between folate and health outcomes beyond neural tube defects remains inconclusive, possibly due to large variations between and within the measurement of folate. With folate measured in diet and blood, we assessed the relationship between folate and the risk of dying from cardiometabolic diseases.

Methods: We analyzed the data of adults aged 19 or older with hypertension who participated in the third National Health and Nutrition Examination Survey (1991-1994) as the baseline examination and were followed up through December 31, 2010. Exposure variables included dietary, serum, and red blood cell (RBC) folate and outcome variables were cardiovascular disease and diabetes mortalities. Cox regression was used to estimate hazard ratios (HRs) of cardiovascular disease and diabetes deaths for participants with dietary, serum and RBC folate in high quartile compared with those with interquartile and low quartile.

Results: After 18 years of follow-up, 579 cardiovascular disease and 165 diabetes deaths were recorded. The cardiovascular disease mortality was 13.04, 16.95, and 26.61/1,000 person-year respectively for the groups with low, inter and high quartile of RBC folate and their corresponding HRs were 1.09 (0.94 – 1.27), 1.00 (reference), and 1.44 (1.31 – 1.58), respectively. No association was detected for the overall association between dietary folate intake and diabetes for men and women combined. Women with upper quartile folate intake, however, had a significantly lower risk of dying from diabetes compared to women with low intake, HR = 0.70 (0.52 - 0.93). The adjusted HRs of diabetes death were 1.00 (reference), 0.94 (0.79 – 1.13) and 1.43 (1.18 – 1.73) respectively for groups with low, intermediate, and high serum folate. The corresponding HRs for RBC folate were 1.00 (Reference), 2.02 (1.84 - 2.21) and 3.12 (2.67 - 3.66) respectively.

Conclusions: We found no association between dietary folate and cardiometabolic deaths, however, high RBC folate was significantly associated with an increased risk of dying from cardiovascular diseases, especially acute myocardial infarction. RBC folate could be used in clinical practice to monitor the progression of existing cardiometabolic health conditions and adjust treatment plans.

Research Data and Supplementary Material