Is Viagra the Most Potent Heart Disease Drug?

Erectile dysfunction (ED) is associated with heart disease, which is logical, since erections depend on the circulation of blood, and arteries must be in a healthy state for both erectile function and heart health. The relation between the two conditions allows us to ask, is Viagra the most potent heart disease drug?

Viagra and similar drugs are associated with vastly fewer heart disease deaths

A just-published study took a look at a large number of Swedish men, 43,145 to be exact,  7.1% of whom got treatment for ED. Then the researchers looked at who died, had a heart attack, or who had heart failure. “Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction.”

Men who got treatment for ED with Viagra had a large reduction in both deaths and hospitalization for heart failure. Reduction in deaths was 33% overall, 40% for heart failure.

Importantly, reduction in death rates appears to be dose dependent.

Men who got 1 prescription for Viagra had 34% fewer deaths.
Men who got 2 to 5 prescriptions had 53% fewer deaths.
Men who got greater than 5 prescriptions had 81% fewer deaths.

Only men who got Viagra for ED had lower death rates. There was no association with death rates for those who got another form of treatment for ED, alprostadil.

What in the world is going on here? The answer can lead us to the true cause of heart disease.

Nitric oxide

Viagra (sildenafil), and the other drugs in this class, such as Cialis and Levitra, are inhibitors of an enzyme abbreviated PDE5, hence they’re called PDE5 inhibitors. They result in an increase in nitric oxide in endothelial cells, which form the lining of blood vessels. In turn, nitric oxide (NO) dilates blood vessels and is critically important in maintaining vascular health.

NO has been implicated in a number of cardiovascular diseases and virtually every risk factor for these appears to be associated with a reduction in endothelial generation of NO. Reduced basal NO synthesis or action leads to vasoconstriction, elevated blood pressure and thrombus formation… Appropriate pharmacological or molecular biological manipulation of the generation of NO will doubtless prove beneficial in such conditions.

The study on Viagra and heart disease deaths only shows association, not causation, and the researchers caution that men who took Viagra may have been in better health to begin with, although none of the men in the study had had a heart attack at the start of the study.

But we can see a mechanistic link between Viagra, which dilates blood vessels that allow erections, and less heart disease, due to better blood vessel function, lower blood pressure, and lower tendency to form blood clots.

Viagra blows statins out of the water

Statin drugs are used to lower cholesterol and allegedly prevent coronary artery disease.

In high-risk populations, that is, in people with existing coronary artery disease, a meta-analysis showed that statins had no statistically significant effect in decreasing death rates.

Earlier studies found a benefit to statins, but we need to keep in mind the biases in studies funded by pharmaceutical companies. After 2004, when full disclosure regulations came into effect, statins appear to have stopped working. That is, studies done before full disclosure found lost of benefit, afterwards they found little to no benefit.

Either way, Viagra showed a huge reduction in deaths, much greater than statins.

Nitric oxide and heart health

The working of the lining of blood vessels, or endothelial function, is critical for arterial health, and endothelial dysfunction is a marker of atherosclerotic disease.

Endothelial dysfunction is a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but rather, may be regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual.

Nitric oxide, as we saw above, is a crucial mediator of endothelial function.

Insulin resistance is strongly associated with heart disease. And insulin resistance causes endothelial dysfunction.

Given the huge reduction in death rates with Viagra as compared to statins, and assuming a mechanistic link between Viagra and the reduction, it sure looks like endothelial function, as mediated by nitric oxide, is far more important to heart disease than cholesterol.

How to increase nitric oxide and endothelial function

Besides Viagra, what else improves endothelial function through increases of nitric oxide.

Citrulline, a supplemental amino acid, treats erectile dysfunction and improves exercise performance. It does this through increasing nitric oxide signaling.

Vitamin D increases endothelial function.

Exercise increases flow-mediated dilation, the measure of endothelial function. “This may contribute to the benefit of regular exercise in preventing cardiovascular disease.” – Understatement of the year.

Iron massively decreases nitric oxide synthase activity, and iron chelators increase it.

For more on how to increase your health and lifespan, try a copy of Dumping Iron,  acclaimed by the world’s leading authority on iron and health, Leo Zacharski, M.D.

PS: Check out my Supplements Buying Guide for Men.

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24 comments
Steve Parker, M.D. says March 20, 2017

Interestingly, Viagra was investigated years go by Pfizer as a cardiovascular drug, not as an ED remedy. From FoxNews:

“Originally, we were testing sildenafil, the active drug in Viagra, as a cardiovascular drug and for its ability to lower blood pressure,” Dr. Brian Klee, senior medical director at Pfizer, told French news agency, AFP. “But one thing that was found during those trials is that people didn’t want to give the medication back because of the side effect of having erections that were harder, firmer and lasted longer.”

Reference Link: http://www.foxnews.com/story/2008/03/24/discovered-by-accident-viagra-still-popular-10-years-later.html

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Bill says March 21, 2017

PD, given that Citrulline, Arginine, Viagra & Vitamin D all help to improve NO and thus arterial function, which do you think should be preferred ?

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    P. D. Mangan says March 21, 2017

    You should ensure adequate vitamin D levels first. After that, citrulline is to be preferred to arginine, since arginase in the intestinal lining breaks down most of the arginine before it gets absorbed. Although it does appear that Viagra has a stronger effect on nitric oxide than citrulline.

    Reply
    Bill says March 21, 2017

    Thanks PD. I will switch over as my supply of arginine powder runs low. Here in Oz viagra is only available as a prescription from chemists and quite expensive. My GP warned me once that a lot of the web sourced viagra was contaminated or contained very low amounts of active ingredient

    Reply
Is Viagra the Most Potent Heart Disease Drug? says March 21, 2017

[…] post Is Viagra the Most Potent Heart Disease Drug? appeared first on Rogue Health and […]

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MG says March 21, 2017

The Swedish ED+viagra study mentions an interesting fact about the “survivors” : “men with ED were more likely to ever discussed ED with their general practitioner if they were married or had higher education”; and then the authors talk about cognitive biases such as confounding bias and immortal time bias. Very powerful study, that’s all I can say.

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    Bill says March 21, 2017

    This Swedish study is a bit odd.It seems as if the authors of the study having found out that viagra helps prevent heart disease deaths, wanted in the discussion, to downplay the significance of their results. Maybe embaressed ? But as you say MG the actual results are powerful.

    Reply
MG says March 21, 2017

Folic acid seems to help as well: check this paper ===> Folate Improves Endothelial Function in Coronary Artery Disease An Effect Mediated by Reduction of Intracellular Superoxide?

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    Bill says March 21, 2017

    That’s a very interesting study MG. 5 mg of folate a day for 6 weeks improved endothelial function significantly. The study notes that this amount is far higher than can be obtained from diet.

    However it is from 2002 which is a while ago now. I wonder if there were any follow up studies on folate.

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JP says March 21, 2017

It is too bad viagra is expensive as hell. If you were going to take it as a supplement, how often would you take it, and at what dose?

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    Scout says March 21, 2017

    The patent for Sildafenil citrate, the active ingredient of Viagra, has expired. So you can buy some cheap generics, too. E.g. this one

    https://peptidepros.net/product/sildenafil-citrate-25mg-per-ml-30ml-bottle/

    25 mg a day should be more than enough for a healthy dude.

    Reply
      P. D. Mangan says March 21, 2017

      Scout, thanks. Nothing I like better than expired patents, and the stuff at that link is very cheap.

      Reply
        Bill says March 21, 2017

        What do you make of this warning at that website for out of patent viagra ?
        “Sildenafil Citrate is for research use only. Sildenafil Citrate is NOT
        for human use and can be harmful if ingested. Sildenafil Citrate should not be misbranded, misused or
        mislabeled as a drug, food or cosmetic.”

        Bit bizarre !

        Reply
    P. D. Mangan says March 21, 2017

    Unfortunately a very difficult question to answer. Viagra has a half-life of 4 hours; however, it may actually upregulate the expression of nitric oxide synthase, so it might not be necessary to take it all that often. Much more research is needed.

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MG says March 21, 2017

Sexual Dysfunction in Diabetic Men (1973): the onset of impotence was gradual, with a period of time during which there was a decreased firmness if the erection but not a total absence of the erectile response. However, in men with impotence of more than one year duration, total loss of erectile function was described by 54 of 57 men…. The means for testosterone in the impotent diabetic men 627 ng/dL and the group without impotence were remarkably similar . A subject with documented Hemochromatosis had a plasma testosterone of 256 ng/dL. The subject reported markedly depressed libido, in contrast to the normal libido described by the rest of the men involved in the study.

Apparently there is no correlation between total testosterone and ED, what caught my eye is the low value found in the Hemochromatosis patient.

From the paper (“GH and sexual health”): Genetic Hemochromatosis (GH) is 10 times more frequent in men than women, GH is rarely diagnosed before the age of 20 years; the peak incidence is 40-60 years. There should be a high degree of suspicion in middle-aged men presenting with cardiac disease who do not have risk factors for coronary heart disease and in individuals with diabetes with no family history or other risk factors.

A high proportion of men with GH suffer from sexual dysfunction. in a study it was found that 46% of men with GH had low libido and 29% impotence, prior to diagnosis.

The aetiology of sexual dysfunction associated with GH is multifactorial. Iron is deposited in the gonadotrophs of the anterior pituitary gland, impairing the release of LH and FSH, leading to hypogonadotropic testicular failure manifest as loss of libido and impotence.

From the last paper it seems that High levels of iron can lead to ED.

cheers,

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    P. D. Mangan says March 21, 2017

    MG, thanks for that. I saw a paper myself that said that diabetic men with impotence had normal testosterone, and iron could very well explain their condition.

    Reply
skinnylegsandall says March 21, 2017

Everyday that young blonde called my name out,half a 50 milligram twice a day. lol

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Allan Folz says March 21, 2017

This is pretty funny. I had heard they discovered Viagra investigating heart disease treatment years and years ago. I can’t recall exactly, but I thnk it was part of the standard news-cycle hype when it first came out. It never occurred to me, or apparently anyone else, to stop and ask, “well, is it any good for heart disease.”

Come to think of it, I’m not surprised they buried those results. If it’s a life-saving CVD treatment people might complain if you’re charging $20 a pill, at least back in the 90’s when Big Pharma pretended to some shame. If it’s a completely discretionary quality-of-life drug, well, much hard to argue over price from the moral high-ground.

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Nathan V says March 22, 2017

To expand on the vitamin D connection:

UVA exposure induces nitric oxide (NO*) production. It has been suggested that NO* protects the skin for 20-30 minutes from UV damage, offers cardiovascular protection, helps wounds and have some anti-tumor activity.

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Science and Technology links (March 24, 2017) | A bunch of data says March 24, 2017

[…] Viagra not only helps with erectile dysfunction, it seems that it keeps heart disease at bay too. But Viagra is out of patent at this point, so pharmaceutical companies are unlikely to shell out millions to market it for other uses. Maybe the government or academics should do this kind of research? […]

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JohnD says March 24, 2017

It seems to me the fitter an older man is, the more likely he is to have a partner for whom he would want to take Viagra. And hence the correlation. E.g. Grossly out of shape old man = no sexual partner = no need for viagra.

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Bill says March 24, 2017

PD, Can I contribute from an Australian perspective ? Here we have a national funded Prescription benefits scheme. Prescription drugs that are listed on the PBS are subsidised by the state.

What’s interesting is that Viagra was never listed on the PBS. It was available but because it was prescribed as only as an ‘erectile disfunction’ drug And it is (was) expensive unless ordered via the web. And it was publicised here as a drug only used by sex addicts. with lots of sniggering.

I suspect that knowledge that it was an excellent heart disease drug was suppressed. I certainly did not know until I read your post here. Meanwhile statins which are ineffective, are promoted for folks with heart problems and are subsidised by the state as they are on the PBS..

Now that is a significant political issue, at least here in Australia.

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Bill In Oz says March 24, 2017

PD I have been looking around for other research papers on viagra ( sildenafil ) as a heart disease drug. I found this one from 2009. https://www.ncbi.nlm.nih.gov/pubmed/19627292

The article concludes as follows “NO is an important mediator for vascular homeostasis and plays an important role in HF. Lack of bio-availability of NO could contribute to the hemodynamic deterioration observed in HF. Apparently, the availability of actions of NO can be enhanced not only by NO donors, but also by the selective inhibitor of PDE5 sildenafil. Sildenafil has been shown to lower pulmonary vascular resistance, increase exercise capacity, and improve RV ejection fraction and the well-being of patients with chronic LV systolic HF.

It seems that its beneficial effects are achieved (at least some) by improving endothelial function in the vascular bed in the periphery and pulmonary blood vessels. Sildenafil can be used as a long-term treatment without the development of tolerance or systemic side effects. Sildenafil can be added to the regular medical arsenal to treat patients with systolic HF. Patients with HF who have already developed secondary pulmonary hypertension may benefit the most from this new approach.”

The side bar for the page lists other articles for similar research going back before 2003.

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    P. D. Mangan says March 25, 2017

    Interesting, I didn’t know it had been advocated for that.

    Reply
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