Q&A with David Goldfarb, M.D.
Professor of Medicine and Physiology, Clinical Chief, Nephrology Division, NYU Medical Center, and Chief, Nephrology Section, New York Harbor VA Medical Center

Dr. Goldfarb, a kidney specialist, was one of the principal investigators on a large nationwide study to determine whether supplements of folic acid and B vitamins could prolong the lives of patients with chronic kidney disease.

Q: This was a huge study. More than 2,000 people participated at 36 VA Medical Centers nationwide, and it cost $9.5 million and took 9 years to plan and carry out. Why was it undertaken?

A: Kidney disease patients die from vascular disease—heart attacks and strokes. The reason isn’t well understood, but we suspected that it could be due to high levels of homocysteine. Based on observational studies, high levels of homocysteine [an amino acid] appeared to be as powerful a risk factor for vascular disease as cholesterol and smoking. Patients with advanced kidney disease have the second-highest levels of homocysteine after patients with homocystinuria, a rare genetic disorder.

Q: Why were high doses of folic acid and B vitamins used in the study?

A. It is well known that these supplements reduce homocysteine in the blood. Patients with kidney disease need higher doses than people with normal kidney function to have this effect. So the study tested whether bringing down homocysteine levels with high doses of folic acid and B vitamins could prolong the lives of kidney patients. The results were negative. The supplements didn’t prolong life or reduce the incidence of vascular disease even though they dramatically lowered homocysteine levels in patients.

Q: Do the supplements help people without kidney disease? 

A: They do not. Two other big randomized controlled studies, the gold standard for clinical testing, were published last year in The New England Journal of Medicine. They showed that the supplements didn’t benefit people who had a recent heart attack or who had vascular disease.

Q: Should anyone take these supplements?

A: Only people with homocystinuria, which is very rare. You know maybe millions of people are taking folic acid and B vitamins because they are safe and inexpensive. In our study we didn’t find any toxicity from the supplements. We know that high levels of homocysteine are associated with cardiovascular events, but there is no evidence that lowering the levels is good for you.

Q: What can be learned from negative studies?

A: You can’t take epidemiologic data and prove causality. Epidemiology is about observations. The goal of epidemiology is to create hypotheses that have to be tested. Homocystinuria, for example, is associated with atherosclerosis. Could high homocysteine levels in the blood be associated with atherosclerosis in the general population? Yes, there is an association. Can you do something about it? Yes, you can. You can lower the levels. Is that useful? No, it doesn’t improve health.

Q: Should cardiologists stop screening their patients for homocysteine?

A: I believe so, yes. And they should stop prescribing folic acid supplements.