Naples-based study leads to medical breakthrough

Joe Papasidero often awakened in the middle of the night in agony from leg cramps.

The 72-year-old Naples retiree was diagnosed with diabetes 18 years ago and figured he had to endure the cramps due to poor blood circulation.

"I would wake up screaming, the leg cramps felt like a golf ball was attached to the muscle of my leg," Papasidero said. "To stop the cramp, I would stand on my toes and put all my weight on (my leg) to relax the muscle."

Now, he pops a pill instead.

The leg cramps, which used to strike three or four nights a week, virtually have disappeared.

"Since I've taken the medication, it's happened once or twice in the last year," he said.

Papasidero took part in a clinical study conducted by two Naples physicians, and their findings are being submitted to the New England Journal of Medicine and elsewhere for review.

Dr. James Talano, a cardiovascular specialist, launched the study two years ago to examine how L-methylfolate, an active folate, affects blood flow in patients with poor blood circulation. L-methylfolate is the result when folic acid supplements are metabolized in the body. Folic acid is believed to prevent heart disease.

Talano

At the time of the launch, Talano was employed at Cleveland Clinic Naples. He was joined in the study by Dr. Michal Kazimir, a research fellow at the clinic.

About 100 patients from Cleveland Clinic, the NCH Healthcare System and some patient referrals from local doctors were enrolled in the study. A control group of patients was given a prescription of L-methyfolate with vitamins B6 and B12, and their blood flow was measured 90 minutes after taking the medication. They took the medication for eight weeks. A second group of patients was given a placebo.

Talano and Kazimir found that the patients on the medication had a dramatic improvement in their blood flow, as much as a 136 percent, because the medication dilated their blood vessels.

Another benefit is that the medication works in the same way for vast numbers of people who are not able to metabolize over-the-counter folic acid, Talano said.

Kazimir

"This is significant for the 45 percent of the population who can't metabolize over-the-counter folic acid," Talano said. "What we are saying is if you have vascular disease, we have found that L-methylfolate with B6 and B12 causes your vascular disease to improve, to improve your blood flow. We know there is an immediate direct effect."

Talano designed the study with initial funding from Cleveland Clinic and approached officials at PamLab LLC, a Covington, La. -based company, to use its product, Metanx, which is L-methylfolate and B6 and B12, for the study.

Metanx is classified by the U.S. Food and Drug Administration as a medical food, a dietary supplement to reduce homocysteine, an amino acid in the blood that accumulates and may promote fatty deposits in blood vessels and increase risk of cardiovascular disease. The medication for lowering homocysteine in patients has been on the market since spring 2005.

Talano left Cleveland Clinic before his study was done and PamLab provided supplemental money to continue it.

Once the two-year study was completed, all the patients who participated were prescribed Metanx because of the benefits, he said.

"We found improved vascular circulation after 90 minutes, and that effect will be long-term with continued use," Kazimir said, who is now a resident at Lehigh Valley Hospital in Allentown, Pa.

Dr. Michael Flynn, a cardiovascular specialist in Naples who prescribes Metanx to patients to lower their homocysteine, said he's not familiar with Talano's study but is interested in it.

"It certainly is thought-provoking and may lead to a bigger study," Flynn said, referring to improving blood flow for cardiac patients and diabetics. "Who knows? Maybe it becomes common practice in two or three years."

Papasidero, one of the study patients, knows for certain he is staying on Metanx, because his leg cramps have just about disappeared and his nights are much more restful.

"I know that the pill works," he said. "If I went off it, I'd be scared I'd get the cramps again."