“One study⁸ demonstrated that a supplement consisting of 5 mg folic acid and 250 μg vitamin B12 lowered fasting plasma homocysteine levels by 32% after 12 weeks in patients with coronary artery disease. In another study⁹ of healthy men and women ranging in age from 70 to 93 years, daily supplementation for 4 months with 500 μg of vitamin B12, 0.8 mg of folic acid, and 3 mg of vitamin B6 significantly reduced plasma homocysteine levels (P < .001). The authors of the study⁹ suggested that suboptimal vitamin status is an important cause of elevated homocysteine even among the healthy elderly.”
A B-12, Folic Acid, and B-6 formulation lowered my homocysteine nicely and I continue to use it but with the awareness that it may be irrelevant. There is evidence to suggest that elevated homocysteine levels are causal to ASCVD, that they are an effect of other cause(s), and/or that they are an intervening variable in the middle of the associative chain. It is even possible that reducing levels could have a negative effect.
My bet (only that) is that homocysteine is involved in the causal chain of ASCVD even though Mendelian Randomization studies generally do not show a strong association between genetically elevated homocysteine levels and increased ASCVD risk. I base my bet on the evidence that homocysteine is thought to promote oxidative stress, leading to nitric oxide depletion and impaired endothelial function, that it has been shown to increase platelet activation, coagulation, and thrombus formation, and that it is associated with oxidative damage (ROS):
One wonders if the effects of achieving ultra-low inflammation as measured by the top 3-4 markers would be as good or better than reducing homocysteine.
My big bet, mostly a hunch based on imperfect information, is that the greatest leverage in preventing ASCVD and maybe cancer is achieved by managing inflammation aggressively.
I like using B6/B9/B12 - need to make sure on folate is activated form, or if high folate already change to folinic acid. Betaine is another item to consider adding.
“Elevated Hcy is considered a risk factor for atherosclerosis and cardiovascular events ([4])
The relationship between Hcy and inflammation may contribute to this increased risk”
Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial