Latest Evidence Fails to Link Homosysteine to Cardiovasular Disease

In 1969 K.S. McCully, M.D. published a report of his autopsy findings concerning 2 young victims of the somewhat rare metabolic disease known as homocystinuria (homocysteine in the urine); which is caused by a genetic condition now known as cystathionine beta-synthase (CBS) deficiency and is thought to affect at least 1 in 200,000 to 335,000 people worldwide. McCully noted that the extent of atherosclerotic disease (hardening of the arteries) present in both victims was much more extensive than he would have expected to find in someone who had died from other causes, which led him to postulate that perhaps the high homocysteine levels present in the blood was somehow related to the extensive atherosclerosis.

Over the next 30 years higher blood levels homocysteine were cited as either the direct cause or as a significant contributor in a number of diseases such as Alzheimer’s disease, hardening of the arteries, osteoporosis, and arthritis. Despite the enthusiasm and high expectations generated by these initial studies, there has been only one drawback: therapies that were known to lower homocysteine levels (such as B-complex dietary supplementation) had no demonstrable effect on the course of the diseases that were supposedly caused by homocystine. But why was this happening?

The original studies (those that uncovered the higher levels of homocysteine) were epidemiologic studies. In this type of research large numbers of people with the same clinical diagnosis are evaluated to determine which, if any, factors can be found in the study population that seem to be associated with a particular disease or condition. Once a tentative association is identified, the next step is to determine if changes in the suspected causative or contributing factor (such as vitamins that are known to lower homocysteine levels in the bloodstream) will result in changes in the number of subjects subsequently diagnosed with the disease under investigation.

As of this writing (September, 2006) there has not been a single scientifically validated study demonstrating that lowering the amount of homocysteine present in the bloodstream has any effect on either the number of new cases diagnosed or in an improvement in the signs and/or symptoms already present. The question is thus reduced to a process of exclusion.

If homocysteine is a significant causative factor in cardiovascular disease, then lowering the homocystine level should result in fewer new or subsequent cardiovascular events (such as a heart attack or stroke). Unfortunately, this has not happened for cardiovascular diseases and the earliest reports regarding Alzheimer’s disease or osteoporosis do not give any reasons to suspect that these conditions will fare any better in the years to come.

Fortunately, although elevated homocysteine is no longer regarded as a major risk factor for cardiovascular disease, the newest guidelines from the American Heart Association (AHA) and



of Cardiology (ACC) have been strictly evaluated and found to be of benefit regarding both the initial and subsequent occurrences of health “events” such as heart attack or stroke.

And you can’t beat the price on these guidelines either: they’re free

Materials Consulted

Fisher, M et al. Nutrition and Stroke Prevention. Stroke. 2006; 37:2430 [Abstract].

Lichtenstein, AH (Chair) et al. Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement from the American Heart Association Nutrition Committee. Circulation. 2006; 114:82-96 [Full Text].

McCully, KS
. Vascular pathology of hyperhomocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969; 56:111-28.

National () Stroke Association. NSA Complete Guide to Stroke. Centennial (CO), : Undated. Sacco, RL (Chair) et al. Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack. Circulation. 2006; 113:e409-e449 [Full Text]. Kaul, Sanjay et al. Homocystine Hypothesis for Atherothrombotic Cardiovascular Disease Not Validated. J Am CollCardiol. 2006; 48:914-923 [Abstract]. The Heart Outcomes Prevention Evaluation (HOPE).Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease. N Engl J Med 354:1567-1577 [Abstract].


The information presented in this article and its included links is of an informational nature only and is not intended as a recommendation of any changes in the reader’s health care program. Before making any changes in diet, medications, or other treatments the reader is strongly advised to consult with their health care provider.

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