Vitamin C, fish, and a gout drug target artery damage from smoking

DALLAS, Jan. 7 – Researchers found that vitamin C and taurine, an amino acid in fish, reversed abnormal blood vessel response associated with cigarette smoking – a discovery that may provide insight into how smoking contributes to "hardening of the arteries," according to an Irish study in today's rapid access issue of Circulation: Journal of the American Heart Association.
In a second study, researchers from Iowa demonstrated that a drug used to treat gout – allopurinol – rapidly reversed the abnormal blood vessel constriction caused by smoking.

"When blood vessels are exposed to cigarette smoke it causes the vessels to behave like a rigid pipe rather than a flexible tube, thus the vessels can't dilate in response to increased blood flow," says David J. Bouchier-Hayes, M.D., senior author of the taurine study and professor of surgery at the Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin. This is a condition called endothelial dysfunction.

Endothelial dysfunction is one of the earliest signs of the atherosclerosis, which is a major cause of heart attacks and stroke. "We're not trying to find a therapeutic treatment for smoking, because we believe that the best therapy for smokers is to stop smoking," says Bouchier-Hayes. "Nonetheless, smokers provide a good clinical model for treatment of endothelial dysfunction."

Bouchier-Hayes and colleagues recruited 15 healthy smokers aged 20 to 37 and 15 healthy non-smoking volunteers. The smokers were given either two grams per day of vitamin C for five days or 1.5 grams per day of taurine. Smokers then waited for a two-week "wash-out" period and switched therapies for five more days.

Researchers assessed blood vessel functioning by flow mediated dilation (FMD), which takes ultrasound images of blood vessel diameter in the arm after a tourniquet was placed on the forearm. Greater diameter after FMD assessment indicates good endothelial function. They assessed FMD at baseline and after taurine and vitamin C supplementation.

The researchers report that taurine restored normal vessel function according to FMD measurements. At baseline, non-smokers' blood vessel diameter was 3.39 mm and smokers' diameter was 3.33. Before treatment, FMD increased dilation in non-smokers to 3.7 mm, while smokers' vessels were virtually unchanged at 3.36 mm after FMD. When they took vitamin C, smokers' vessel diameter increased to 3.45 mm after FMD. When the were given taurine, the smokers' vessel response was the same as the non-smokers' at 3.7 mm after FMD.

Taurine is found in many foods but is most abundant in fish, says Bouchier-Hayes, who adds that taurine is present even in mild, white fish not just fatty fish. The taurine supplement used in the study is equivalent that found in one serving of fish.

William G. Haynes, M.D., senior author of the allopurinol study and associate professor of internal medicine, University of Iowa College of Medicine, Iowa City, agrees that treatments that are effective in smokers are likely to be applicable to non-smokers who have similar endothelial dysfunction.

Haynes studied 14 heavy smokers aged 18 to 85 and 14 age- and sex-matched non-smoking volunteers. The subjects underwent tests to assess blood vessel functioning at baseline and after treatment. The subjects were randomized to receive either a single 600 mg oral dose of allopurinol or no drug on the day of the study.

At baseline smokers had impaired blood vessel function as measured by blood vessel dilation in response to the stimulant acetylcholine. A greater change in vessel dilation after acetylcholine indicates better endothelial function. The change in dilation produced by acetylcholine was significantly less in smokers (254 percent) than in non-smokers (390 percent). After taking allopurinol, smokers' response to acetylcholine improved to 463 percent, while non-smokers' response remained about the same (401 percent).

Allopurinol inhibits an enzyme called xanthine oxidase, which increases oxidative stress in the blood vessels. "This is the first study to show that a single oral dose of allopurinol can have rapid and substantial endothelial effects in smokers," says Haynes.

"These studies provide further evidence of the damaging effect cigarette smoking has on blood vessels," says Sidney Smith, M.D., past president of the American Heart Association. "They may also provide insight into the mechanism by which smoking causes injury to blood vessels. This and other evidence further emphasizes the importance of not smoking if one is to avoid the risk of heart attack or stroke."


Bouchier-Hayes co-authors were Fiona M. Fennessy, Ph.D.; D. S. Moneley, M.B.; J.H. Wang, M.D., Ph.D.; and C.J. Kelly, M.B.

Haynes co-authors were Sashi Guthikonda, M.D., M.P.H.; Christine Sinkey, R.N.; and Therese Barenz, R.N. Dr. Haynes' research was partly funded by the National Institutes of Health and by the Iowa Affiliate of the American Heart Association.

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