Vitamin C, taurine, and allopurinol reverse endothelial dysfunction in smokers

January 07, 2003

Tue, 07 Jan 2003 20:00:00

Dublin, Ireland and Iowa City, IA - Smoking-induced endothelial dysfunction can be reversed by the use of vitamin C and taurine supplementation and also by the use of the gout drug allopurinol, 2 new studies show. The results suggest that these approaches could be applied to nonsmokers who have similar endothelial dysfunction, the researchers say.

An author on 1 of the studies, Dr David J Bouchier-Hayes (Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland) says: "We're not trying to find a therapeutic treatment for smoking, because we believe that the best therapy for smokers is to stop smoking. Nonetheless, smokers provide a good clinical model for treatment of endothelial dysfunction." Bouchier-Hayes and colleagues gave vitamin C and taurine, an amino acid found in fish, to a group of smokers and nonsmokers and then assessed blood vessel functioning by flow-mediated dilation (FMD) using ultrasound.

 

Smokers provide a good clinical model for treatment of endothelial dysfunction.

 

Their results, along with those of the study involving allopurinol, led by Dr Sashi Guthikonda (University of Iowa College of Medicine, Iowa City), appear in yesterday's rapid access issue of Circulation.

A piece of fish a day keeps the doctor away

In the study in which Bouchier-Hayes was involved, led by Dr Fiona M Fennessy (Beaumont Hospital, Dublin, Ireland), 15 healthy smokers aged 20 to 37 and 15 healthy nonsmoking volunteers were recruited. The smokers were given either 2 g per day of vitamin C or 1.5 g per day of taurine for 5 days. Smokers then waited for a 2-week "wash-out" period and switched therapies for 5 more days.

The researchers assessed functioning of the brachial artery by FMD. Greater diameter after FMD assessment indicates good endothelial function. They assessed FMD at baseline and after taurine and vitamin C supplementation. Before treatment, FMD increased dilation in nonsmokers to 3.7 mm (see table) while smokers' vessels were virtually unchanged. When they took vitamin C, smokers' vessel diameter increased to 3.45 mm after FMD. When they were given taurine, the smokers' vessel response was the same as the nonsmokers' at 3.7 mm after FMD.

Actual brachial artery diameter measurements at baseline conditions and after FMD in smokers, nonsmokers, and smokers supplemented with vitamin C and taurine


Group

Baseline (mm)

After FMD (mm)

p

3.39
3.7
<0.0007
3.33
3.36
NS
3.33
3.45
<0.0005
3.33
3.7
<0.0005
To download table as a slide, click on slide logo below

Fennessy et al also looked at monocyte-conditioned medium (MCM) taken from the smokers and cultured with human umbilical vein endothelial cells (HUVECs) to assess monocyte-endothelial interactions. They found that MCM from smokers impaired the release of nitric oxide and increased the levels of endothelin-1 release from HUVECs. But when HUVECs were cultured with MCM from smokers who had been treated with taurine, the levels of nitric oxide and endothelin 1 returned toward control levels, which they attribute to an up-regulation in endothelial nitric oxide synthase expression. However, they were unable to identify the mediator or mediators responsible for the down-regulation of endothelial nitric oxide synthase attributed to smoking.

 

An evaluation of taurine's effect on altered endothelial function in dyslipidemic states is warranted.

 

Taurine is found in many foods but is most abundant in fish and is present even in mild, white fish, not just fatty fish. The taurine supplement used in the study is equivalent to that found in 1 serving of fish, the researchers note. Taurine "seems to be remarkably free of toxicity and has been used clinically in similar or greater doses in patients with diabetes mellitus and congestive cardiac failure," they note. Given their findings, they conclude that "an evaluation of taurine's effect on altered endothelial function in dyslipidemic states is warranted."

Xanthine oxidase inhibition reverses endothelial dysfunction

Meanwhile, Guthikonda et al studied 14 heavy smokers aged 18 to 85 and 14 age- and sex-matched nonsmoking volunteers. They explain that damage to the vascular endothelium, such as is produced by cigarette smoking, possibly occurs through production of oxygen free radicals. Several enzymes can produce oxygen free radicals, such as xanthine oxidase, which is inhibited by the gout drug allopurinol. No previous studies have tested whether inhibition of xanthine oxidase improves endothelial function in cigarette smokers, they note, nor has anyone looked at the effects of a single oral dose of allopurinol on vascular function.

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 and after treatment, stimulated nitric oxide endothelial responses were assessed by forearm blood flow using venous occlusion plethysmography in response to acetylcholinea greater change in vessel dilation after acetylcholine indicates better endothelial function. At baseline, smokers had impaired forearm blood flow in response to acetylcholine. The change in dilation produced by acetylcholine was significantly less in smokers (254%) than in nonsmokers (390%). After taking allopurinol, smokers' response to acetylcholine improved to 463%, while nonsmokers' response remained about the same (401%).

 

This is the first study to show that a single oral dose of allopurinol can have rapid and substantial endothelial effects in smokers.

 

"This is the first study to show that a single oral dose of allopurinol can have rapid and substantial endothelial effects in smokers," says Dr William G Haynes (University of Iowa College of Medicine, Iowa City), a coauthor of the study. This suggests than xanthine oxidase plays a role in endothelial dysfunction, but further studies are needed "to elucidate the exact mechanisms of xanthine oxidase actions on the endothelium," the researchers conclude.

Further evidence of damaging effects of smoking

"These studies provide further evidence of the damaging effect cigarette smoking has on blood vessels," Dr Sidney Smith (past president of the American Heart Association) comments in an AHA news release. "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."



Related links

1. [HeartWire > News; Jun 19, 2002]

2. [HeartWire > News; Oct 29, 2001]

3. [HeartWire > News; Jul 24, 2001]

4. [HeartWire > News; Jul 10, 2001]

5. [HeartWire > News; Jun 26, 2000]

6. [HeartWire > News; May 5, 2000]


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