Disease Proof

Gina Kolata writes in The New York Times:

A widely promoted B-vitamin regimen for the prevention of heart attacks and strokes has shown no beneficial effects in people at high risk, researchers are reporting in two new studies.

The widely accepted hypothesis was that B vitamins -- folic acid, vitamin B12 and vitamin B6 -- could protect against homocysteine, an amino acid that some doctors said was as important and dangerous a risk factor for heart disease as cholesterol.

Studies of populations had shown that the higher the homocysteine level in the blood, the greater the risk of heart attacks and strokes. And studies of animals had indicated that homocysteine could actually damage the tender linings of arteries, setting the stage for atherosclerosis.

B vitamins, however, reduce blood levels of homocysteine. The vitamins, which are found in a variety of foods, have no known harmful effects. And if people take the vitamins as supplements, their homocysteine levels plummet. About 35 percent of Americans take B vitamins, mostly in the form of multivitamin pills, according to the Council on Responsible Nutrition, a trade group.

So it seemed reasonable that taking the vitamins would be protective. It might be even better than taking statin drugs, some said, which are well established to prevent heart disease by lowering cholesterol levels.

It was not, the new studies found.

This is another example of the blind leading the blind. The problem is the way research is conducted in general and our typical medical approach in trying to give every patient some cookbook response to their high homocysteine level, rather than treating every patient as an individual.

High Homocysteine Levels Are Markers for Poor Diet
In my experience, a high homocysteine level is mainly important as a marker indicating a diet low in vegetables, especially the folate rich greens. In other words, it is one of the blood signs of a poor diet.

Fixing the homocysteine level without fixing the diet shouldn't be expected to do much because it is hundreds of important nutrients and factors that are missing not just the folate. A pill can't take the place of the symphonic effect of a diet that is naturally folate and nutrient rich.

One of the researchers quoted in The New York Times, Dr. Salim Yusuf of McMaster University in Hamilton, Ontario, has a similar, but vaguer idea. Again, Gina Kolata:

The most likely explanation for the studies' results, Dr. Yusuf said, was that homocysteine levels were not the cause of disease. Instead, he said, they are probably a sign of heart disease, much like fever is a sign of infection. Treating a fever with aspirin does not cure the infection, and lowering homocysteine levels with B vitamins does not cure disease either.

The Bottom Line For Your Health: High Homocysteine Levels Still Must be Addressed These studies show that homocysteine lowering therapies do not work on a gross scale to reduce heart attack deaths---but that does not mean that a person who has a significant homocysteine elevation should not address the cause of such an elevation.

I am in the process of revising my book Cholesterol Protection For Life (the new version will be available in about a month) and recently wrote about this issue. Here are some relevant excerpts:

Is homocysteine an important indicator of heart disease?

Maybe and maybe not, it depends on how high your homocysteine level is and the cause of the elevation. Homocysteine is an independent risk factor for heart disease. That means even if your cholesterol is favorable, heart disease can sometimes be caused by an elevated homocysteine.

A high homocysteine can also be a contributory cause of high blood pressure and place you at higher risk of stroke. Homocysteine can be elevated secondary to increased need for B12, B6 or folate. It is rare, but still possible for a person with a perfect diet and ideal cholesterol levels to develop chronic disease from an elevated homocysteine level.

Theoretically, most people eating a plant-based diet rich in vitamins, especially folate, only have to be concerned with consuming adequate B12 to assure a normal homocysteine level. However, there are other causes. Some uncommon cases of individuals who have a very high homocysteine level, normal B12 (documented by a methylmalonic acid, MMA test) and also normal folate levels on blood tests. These people should be instructed to take extra folate as they likely have a genetic defect converting folate to its more active form.

After reviewing scores of medical studies on the relationship between high homocysteine and the increased risk of Alzheimer's, stroke, heart attack and dementia one has to conclude that there is a clear cut relationship between high homocysteine and serious disease. However, this is a complicated subject, where confusion abounds, and the right way to lower homocysteine or whether we should attempt to lower it at all is still debated. Clearly we have more to learn as more time and further research is revealed in years to come.

One reason there is such contradictory information in the scientific literature is because the researchers appear to have such poor working knowledge of excellent nutrition and are not targeting the therapy to match the corresponding cause(s) of the homocysteine elevation. Instead, both researchers and most physicians are simplistically giving the same conventionally-designed, nutritional supplement to a cohort of patients with different causes for the high homocysteine.

Physicians think about high homocysteine as only one problem, like high cholesterol, when there could be multiple reasons for the abnormality, so often the solution does not fit the problem. There should not be a one size fits all solution to an elevated homocysteine.

Homocysteine levels above 20 micro mol/l are associated with a 10 fold increased risk of heart attack compared to levels below 9 micro mol/l. 1 These high elevations of homocysteine should not be ignored. Doing so could result in an easily avoidable medical tragedy.

For example, homocysteine can be elevated from:

• A poor diet, low in folate-containing vegetables.
• A B12 deficiency
• An uncommon defect in conversion of folate to the active form (even in a person eating a healthy diet)
• Kidney disease

Address High Homocysteine Levels With Recommendations Targeted to the Cause
Consider an abnormal homocysteine that may require treatment above 15, not above 10. Levels between 10 and 15 have not been consistently associated with worse outcomes.2
If one homocysteine is elevated above 15, make sure a blood level of B12, and MMA (methlymalonic acid) and a folate level is drawn.

Mild elevations of homocysteine between 10 and 15 do not appear to place people at higher risk. In most of these cases, the mild elevation is just a marker for a low nutrient diet in general and the correct treatment is the improvement of the entire diet, not just a supplement to lower homocysteine. Folate alone in these cases cannot compare with the value of actually eating a diet rich in folate and gaining all the other essential cardio-protective compounds that are found in natural plant foods. It is similar to taking a cholesterol-lowering drug instead of eating healthfully; a pill cannot take the place of the full symphony of dietary elements that contribute to heart and vascular health.

When the abnormality (elevated homocysteine) is due to B12 deficiency it is wise to take more B12. Whether you are consuming sufficient B12 or not is best ascertained by a normal MMA (methylmalonic acid) because a B12 level in the 200 to 400 range, which is considered in the normal range could still be abnormal. Paradoxically, MMA is actually a better marker for B12 deficiency than B12 itself. If the MMA is elevated a B12 deficiency exists, even if the B12 is in the normal range. When this is the case, extra B12 is the correct treatment for the elevated homocysteine.

If the folate level is excellent (15 - 25) and the B12 level is normal (as documented with a normal MMA) and the homocysteine is still significantly elevated,then the cause of the elevation is most likely a genetic defect in folate conversion. In this case, folate (or folic acid) supplementation may not be totally effective; because the patient is just taking more of the folate that they don't convert effectively to begin with. They don't need more folate, rather they need more of the biologically active form of folate that they don't make well (called methyl tetrahydrofolate or formyl tetrahydrofolate.)

So if the B12 is normal and the folate is normal, and the homocysteine is still significantly elevated, it may make more sense to take a supplement containing additional tetrahydrofolate, and not just pile on huge doses of folate (folic acid) attempting to drive the homocysteine down with overwhelming high doses of folate.

In conclusion, it is wise to target therapy based on known deficiencies and not just blanket patients with high dose supplements that they do not need. Nevertheless, an attempt to uncover the cause of the homocysteine elevation and lower it accordingly may be an important intervention for patients with unique needs.

Medical Research Still Has a lot of Questions to Answer About Homocysteine.
In the meantime, it should be recognized that a vegetable-based diet rich in fresh produce with fruit, beans, raw nuts and seeds, naturally low in saturated fat and in sodium is our most powerful protection against disease. It lowers blood pressure as much as drugs and, in heart patients, is at least twice as effective at reducing death rates and heart attacks as drugs.3 The day may come when a physician, who does not offer such a diet to his heart patients is himself at high risk for being sued for malpractice.

1 Spence JD. Patients with atherosclerotic vascular diseases: how low should plasma homocysteine levels go? Am J Cardiovasc Drugs 2001;1(2):85-89.

2 Sacco RL, Anand K, Lee HS, et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the Northern Manhattan Study. Stroke 2004;35(10):2263-2269.

3 Spence JD. Nutritional and metabolic aspects of stroke prevention. Adv Neurol 2003;92:173-178.