From the Guidelines
To lower homocysteine levels, the recommended daily doses are 25-100 mg of vitamin B6, 400-1000 mcg of folic acid, and 500-1000 mcg of vitamin B12, but it's essential to note that supplementation with these vitamins does not necessarily lower the risk of cardiovascular disease. These three B vitamins work together to help break down homocysteine in the body. Vitamin B6 serves as a cofactor for enzymes that convert homocysteine to cysteine, while vitamin B12 and folate are needed for the remethylation of homocysteine to methionine.
Key Considerations
- The most recent and highest quality study, 1, found that homocysteine-lowering interventions did not reduce the risk of fatal/non-fatal myocardial infarction, stroke, or death by any cause.
- Folic acid at a dose of 400 micrograms per day will reduce plasma homocysteine levels by approximately 5 micromoles per liter, and vitamin B12 at doses averaging 0.5 mg daily can decrease homocysteine levels by an additional 7% 1.
- Vitamin B6 (at an average of 6.5 mg daily) had no significant additional benefit in reducing homocysteine levels 1.
- It's crucial to have your homocysteine levels tested before starting supplementation and to follow up with testing after a few months to ensure the supplements are effective.
- Some people may require different dosages based on their specific health conditions, medication use, or genetic factors.
- These supplements are generally well-tolerated, but you should consult with your healthcare provider before starting this regimen, especially if you have existing health conditions or take other medications.
Important Notes
- The European Guidelines on Cardiovascular Disease Prevention in Clinical Practice (version 2012) concluded that B-vitamin supplementation to lower homocysteine levels does not lower the risk of cardiovascular disease 1.
- The Cochrane Collaboration meta-analysis of eight RCTs also found that homocysteine-lowering interventions did not reduce the risk of fatal/non-fatal myocardial infarction, stroke, or death by any cause 1.
From the FDA Drug Label
Although most patients with malabsorption cannot absorb food folates, they are able to absorb folic acid given orally. Doses greater than 0. 1 mg should not be used unless anemia due to vitamin B12 deficiency has been ruled out or is being adequately treated with a cobalamin. Daily doses greater than 1 mg do not enhance the hematologic effect, and most of the excess is excreted unchanged in the urine. The usual therapeutic dosage in adults and children (regardless of age) is up to 1 mg daily. Except during pregnancy and lactation, folic acid should not be given in therapeutic doses greater than 0.4 mg daily until pernicious anemia has been ruled out.
The recommended dose of folic acid to lower homocysteine levels is up to 1 mg daily 2 or up to 0.4 mg daily until pernicious anemia has been ruled out 2.
- Vitamin B12 should be given in adequate amounts to prevent neurologic manifestations due to vitamin B12 deficiency.
- The FDA drug label does not provide specific information on the recommended dose of Vitamin B6 to lower homocysteine levels. The FDA drug label does not answer the question regarding the recommended dose of Vitamin B6.
From the Research
Recommended Intake of Vitamin B6, Folic Acid, and B12 to Lower Homocysteine Levels
The recommended intake of vitamin B6, folic acid, and B12 to lower homocysteine levels is not strictly established, but various studies provide insights into the effective doses:
- Folic acid: Daily doses of 0.5-5.0 mg can lower plasma homocysteine levels by approximately 25% 3. A meta-analysis suggests that daily doses of 0.2,0.4,0.8,2.0, and 5.0 mg folic acid are associated with reductions in homocysteine of 13%, 20%, 23%, 23%, and 25%, respectively 4.
- Vitamin B12: A dose of 0.4 mg/d can produce a 7% further reduction in homocysteine concentrations 4.
- Vitamin B6: The effect of vitamin B6 on homocysteine levels is less clear, but a study suggests that a combination of pyridoxine (50 mg) and folic acid (5 mg) can be effective in treating hyperhomocysteinemia 5.
Effective Combinations and Doses
Some studies suggest the following combinations and doses:
- Folic acid (0.5-5 mg/day) alone or in combination with vitamin B12 (0.4 mg/d) 5, 4.
- A combination of pyridoxine (50 mg), folic acid (5 mg), and vitamin B12 (0.4 mg/d) may be effective in treating hyperhomocysteinemia 5.
- Daily supplementation with 0.8 mg or more of folic acid is typically required to achieve the maximal reduction in plasma homocysteine concentrations produced by folic acid supplementation 4.
Considerations for Specific Populations
For patients with mild cognitive impairment, supplementation with vitamins B6, B12, and/or folic acid can reduce homocysteine levels, with a mean decline of 31.9% in the intervention arms 6. In patients with renal failure, folic acid treatment (1-5 mg/day) can ameliorate plasma homocysteine levels, but hyperhomocysteinemia may persist in the majority of patients 5.