B Vitamins and Folic Acid Are Important, but Not Necessarily for Heart Health
"...it's a revolution in thinking about the origin of heart disease. The cholesterol hypothesis has been that eating an excess of either cholesterol or high fat in the diet somehow causes the elevation of blood cholesterol and somehow damages the arteries. The homocysteine approach attributes the process of arteriosclerosis to a deficiency of B vitamins."
--Dr. Kilmer McCully
For years, Dr. Kilmer McCully staked his career on the idea that homocysteine, an amino acid in blood, was an important - perhaps the most important - and neglected cause for heart disease.
Dr. McCully initially became interested in this concept in 1969 when he noted that children with a genetic defect called homocystinuria developed coronary heart disease and heart attacks as young as their teens and 20s and had extremely high blood and urine levels of the amino acid. He later expanded the hypothesis: If increased homocysteine is related to heart disease in young people, perhaps it is also a cause for heart disease in older adults.
Indeed, many reports over the last 20 years appeared to have proved him right: the higher the homocysteine, the greater the likelihood of heart attack and stroke. Study after study revealed that people with homocysteine levels of 14 micromol/L or greater had triple or more risk.
Homocysteine can be effectively reduced by taking B vitamins: B6, folic acid, and B12, though at higher than usual doses. Initial studies did, indeed, support this part of the argument as well: people with lower blood levels of these B vitamins suffered more heart attacks; supplementation appeared to be associated with reduced risk.
The argument was so compelling that several independent investigations were launched, all designed to answer the question: If homocysteine causes atherosclerotic heart disease, heart attack, and stroke, does supplementation of higher doses of vitamins B6, B12, and folic acid reduce risk?
Well, the eighth study in two years to attempt to answer this question, all applying a B vitamin vs. placebo, in various groups of people, using somewhat varied dose regimens of vitamins, and with varying levels of starting homocysteine, are all in agreement: No, B vitamin supplementation, while it does reduce homocysteine blood levels, does not reduce likelihood of heart attack and stroke.
The latest addition to the growing list of studies discrediting Dr. McCully's homocysteine hypothesis comes from Norway, a study of 3000 participants with coronary disease assigned to one of four treatments: folic acid, 0.8mg, vitamin B12 , 0.4mg, and vitamin B6, 40mg (n= 772); folic acid plus vitamin B12 (n = 772); vitamin B6 alone (n = 772); or placebo (n = 780). Homocysteine levels were reduced by an average of 30% after one year of treatment with folic acid and vitamin B12. After 36 months of observation, there was no difference in the rate of heart attack among any of the groups (all experiencing approximately 13% likelihood of heart attack or stroke).
The Norwegian study can be added to the growing list of studies that pretty much put the question to rest: B vitamin supplementation does not reduce risk for heart attack or stroke.
(Dr. Kilmer McCully has been curiously quiet on these findings. In one editorial, he did comment that he felt the negative findings of these studies were likely due to the 1998 FDA mandate that the U.S. food supply contain supplemental folic acid.)
Does that mean we should toss our B vitamins in the garbage?
No, absolutely not. Despite the now incontrovertible argument that B6, B12, and folic acid do not reduce cardiovascular events, several questions need answering:
- Why does homocysteine serve such a powerful role in predicting heart disease and stroke? Is it a marker for another process? Do B vitamins represent an incomplete solution and something crucial is missing from the treament regimen? Or, is it the wrong treatment altogether?
- Why do children with very high homocysteine levels appear to benefit from B vitamin supplementation?
- Are there subgroups of people with elevated homocysteine that may benefit while others do not? For instance, there are people with a genetic basis for elevated homocysteine that may represent a different pattern than people who have high homocysteines due to vitamin deficiencies.
- Do adults with very high levels of homocysteine, e.g., > 30 micromol/L, differ in some way? Are they more likely to benefit from either B vitamin supplementation or other treatments?
- Are there specific subgroups of people who have been shown to obtain exaggerated risk from elevated homocysteine, e.g., people with lipoprotein(a), a very high-risk pattern for heart disease, who may still benefit from B vitamin supplementation? (Lipoprotein(a) has been shown in several studies to interact with the homocysteine molecule.)
In everyday life, increased homocysteine can also signal deficiencies of vitamins B12 and folic acid, less commonly B6. While supplementation may not address cardiovascular risk, it can prevent anemia, help maintain stamina, improve mental function, and provide other health benefits.
In many ways, the failure of B vitamin supplementation opens more questions than it settles. While the simple notion of B vitamin supplementation and cardiovascular risk seems settled, there are plenty of more issues to explore. Homocysteine research remains a fascinating area that is likely to yield more insights.