Effect of folic acid supplementation on the change of plasma S-adenosylhomocysteine level in Chinese hypertensive patients: a randomized, double-blind, controlled clinical trial

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene­tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45–75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4–2.0 mg/day had no effect on SAH level (β = 0.47, 95% CI: −0.86–1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (β = 1.93, 95% CI: 0.22–3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (β = 0.30, 95% CI: −2.74–3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: β = 2.98, 95% CI: 0.34–5.62, p = 0.027; TT: β = 3.00, 95% CI: −0.51–6.51, p = 0.095; CT combined with TT: β = 2.99, 95% CI: 0.90–5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.