Similarly, in patients with hypertension and hyperhomocysteinemia (18 males and 7 females, age 40–65), reactive hyperemia is improved by 4 weeks oral L-arginine (Reule et al., 2017), administered in a mixture with pycnogenol, which itself activates eNOS (Fitzpatrick et al., 1998); α lipoic acid, which promotes eNOS recoupling (Sena et al., 2008); vitamin B2, which is a cofactor for eNOS; and folic acid, which activates eNOS and prevents its uncoupling (Stroes et al., 2000). Here, NOS3 is linked to hyperhomocysteinemia.