The HOPE-2 Study (Heart Outcomes Prevention Evaluation-2 Study), published in March 30, 2009 in the Journal Stoke, sought to determine whether long term supplementation with folic acid, vitamins B6 and B12 aimed at homocysteine reduction reduces the rates of major fatal and nonfatal cardiovascular events in patients with established cardiovascular disease and/or diabetes mellitus. 1
The aim of the study was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke, as well as stroke-related disability.
Elevated total homocysteine is associated with a higher risk of cerebrovascular disease. It is not known whether lowering homocysteine impacts on stroke risk, both in terms of severity and ischemic vs hemorrhagic stroke subtypes.
The researchers randomized 5522 adults with known cardiovascular disease to a daily combination of:
- Folic Acid 2.5 mg
- Vitamin B6 50 mg
- Vitamin B12 1 mg
or matching placebo, for 5 years.
Homocysteine concentration decreased by 2.2 µmol/L in the B-vitamin therapy group and increased by 0.80 µmol/L in the placebo group. The risk of stroke was reduced by 25% in the B-vitamin therapy group. 2
Metabolically Active Forms of B Vitamins
Folate helps maintain homocysteine levels within the normal range, which promotes cardiovascular health. And it also supports neurotransmitter synthesis — which in turn helps maintain cognitive abilities.
However, not everyone has sufficient activity of the enzyme required to convert folate to its biologically active form, 5-methyltetrahydrofolate, or 5-MTHF. The bioactive 5-MTHF form of folate which is up to 7 times more bioavailable than ordinary folic acid.
Those who take ordinary folate supplements, however, may not be experiencing its full spectrum of effects. This is because once ingested, not everyone converts folate to its biologically active form called 5-methyltetrahydrofolate (5-MTHF). 1
Research shows that in a large proportion of the population, genetic enzyme deficiencies prevent the conversion of folate to 5-MTHF, leaving many vulnerable to low blood folate levels (and higher-than-desired homocysteine).
Pyridoxal 5’-phosphate is the metabolically active form of vitamin B6 that has been shown to protect living lipids and proteins against glycation reactions.
It consists of 67.6% Vitamin B6 and 32.4% Phosphate.
Pyridoxal-5-Phosphate is the form of Vitamin B6 that is actually assimilated by the body’s Cells and Tissues where it participates (as a coenzyme) in many biological reactions, especially transaminations and decarboxylations.
Methylcobalamin is the form of vitamin B12 active in the central nervous system. It is essential for cell growth and replication.8 In some people the liver may not convert cyanocobalamin, the common supplemental form of vitamin B12, into adequate amounts of methylcobalamin needed for proper neuronal functioning.
Methylcobalamin may exert its neuroprotective effects through enhanced methylation, acceleration of nerve cell growth, or its ability to maintain already healthy homocysteine levels. 1
Foods that contain the three B Vitamins
- vegetables (particularly dark green leafy vegetables),
- fruits and fruit juices
- dairy products
The highest levels of folate are found in the following foods: 1
- Brussels sprouts
- Brewer’s yeast
- wheat bran
- wheat germ
- soy beans
Foods that contain large amounts of vitamin B6 include:
Vitamin B12 is found naturally in a wide variety of animal foods. Plant foods have no vitamin B12 unless they are fortified. These foods include:
- beef liver
- lamb liver
- milk, and other dairy products
- Nori seaweed
- Kombu seaweed