From the Guidelines
Folate and homocysteine levels are inversely related, with adequate folate helping to keep homocysteine levels in check, but supplementation with folic acid and vitamin B6 and/or B12 does not lower the risk of cardiovascular disease. Folate (vitamin B9) is an essential nutrient found in leafy greens, legumes, and fortified foods that plays a crucial role in DNA synthesis and repair. It also serves as a methyl donor in the conversion of homocysteine to methionine. Homocysteine is an amino acid produced in the body during protein metabolism, and elevated levels are associated with increased risk of cardiovascular disease, stroke, and cognitive decline. When folate levels are insufficient, homocysteine cannot be efficiently converted to methionine, causing homocysteine to accumulate in the bloodstream.
Some key points to consider:
- The recommended daily intake of folate is 400 mcg for most adults, with pregnant women needing 600 mcg daily.
- Supplementation with folic acid (the synthetic form of folate) at 400-1000 mcg daily can effectively lower homocysteine levels in people with hyperhomocysteinemia, as shown in a meta-analysis of randomized trials of homocysteine-lowering vitamin supplements 1.
- Other B vitamins, particularly B6 and B12, also participate in homocysteine metabolism, so deficiencies in these vitamins can similarly lead to elevated homocysteine levels even with adequate folate intake.
- However, recent studies have shown that supplementation with folic acid and vitamin B6 and/or B12 does not lower the risk of cardiovascular disease, as concluded by the Cochrane Collaboration in a meta-analysis of eight RCTs and three large secondary prevention trials 1.
In terms of managing homocysteine levels, it is essential to focus on a balanced diet rich in folate, B6, and B12, rather than relying on supplementation, as the current evidence does not support the use of B-vitamin supplementation to lower cardiovascular risk.
From the Research
Folate and Homocysteine Levels
- Folate, also known as vitamin B9, plays a crucial role in the metabolism of homocysteine, an amino acid in the blood 2, 3, 4, 5.
- Homocysteine is a sulfur-containing intermediate product in the normal metabolism of methionine, an essential amino acid 2.
- Elevated plasma homocysteine levels (> 12 micromol/l) are considered cytotoxic and are found in 5 to 10 percent of the general population and in up to 40 percent of patients with vascular disease 2.
Relationship Between Folate and Homocysteine
- Folic acid deficiency is considered the most common cause of hyperhomocysteinemia 2, 3, 4.
- An adequate intake of at least 400 microg of folate per day is difficult to maintain even with a balanced diet, and high-risk groups often find it impossible to meet these folate requirements 2.
- Daily supplementation with 0.5-5.0 mg of folic acid typically lowers plasma homocysteine levels by approximately 25% 3.
- A combination therapy with B vitamins--folate, vitamins B12 and B6 is an effective means to reduce elevated homocysteine levels in general people and in patients with myocardial infarction 5.
Effects of Folate Supplementation on Homocysteine Levels
- Supplementation with vitamins B6, B12, and/or folic acid has been shown to reduce homocysteine levels in patients with mild cognitive impairment 6.
- Folic acid supplementation should be recommended to any patient who has an elevated homocysteine level, and this level should be measured and treated at an early age 3.
- Alteration in dietary intake or use of folic acid supplements can substantially lower homocysteine concentrations 4.