Relationship of several serum folate forms with the prevalence of hypertension

Background: The relationship of different serum forms of folate with the prevalence of hypertension remains uncertain. We aim to examine the association of several folate forms (5-methyltetrahydrofolate [5-mTHF], unmetabolized folic acid [UMFA], and MeFox [an oxidation product of 5-mTHF]) with the prevalence of hypertension. Methods: This cross-sectional study included 19,237 participants from the National Health and Nutrition Examination Survey 2011–2018. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, or a self-reported diagnosis of hypertension by a physician, or current anti-hypertensive treatment. Results: The prevalence of hypertension was 39.3%. When serum 5-mTHF was assessed as quartiles, a significantly lower prevalence of hypertension was found in participants in quartiles 3 to 4 (≥34.0 nmol/L) (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.76–0.97), compared with those in quartiles 1 to 2. When serum UMFA was assessed as quartiles, a significantly higher prevalence of hypertension was found in participants in quartile 4 (≥1.0 nmol/L) (OR, 1.16; 95% CI, 1.03–1.31), compared with those in quartiles 1 to 3. When serum MeFox was assessed as quartiles, a significantly higher prevalence of hypertension was found in participants in quartiles 3 to 4 (≥1.4 nmol/L) (OR, 1.19; 95% CI, 1.06–1.34), compared with those in quartiles 1 to 2. Conclusions: Higher serum 5-mTHF levels were associated with a lower prevalence of hypertension, while higher serum UMFA and MeFox levels were associated with a higher prevalence of hypertension. If further confirmed, our findings highlight the importance of monitoring different serum forms of folate and may help guide future clinical trials and nutritional guidelines on folic acid supplementation for prevention of hypertension.