What causes heart disease part XXVIII


For those who have read my endless series of blogs on cardiovascular disease, you may know exactly where I am going at this point.

Some time ago, Pfizer were developing a drug to treat angina. It blocked an enzyme called phosphodiesterase type-5. [Although I believe that its exact mechanism of action was not known at first]. To put it another way, this drug was a phosphodiesterase type-5 inhibitor (PDE5i).

The moment Pfizer found out what enzyme this drug blocked, they tried to patent the pathway that blocked this enzyme. Pharmaceutical companies trying to patent biological pathways. Perhaps I should try to patent the Krebs cycle, and charge everyone on the planet for having such a thing. Kerchingggg!

‘The U.S. patent office appears to have granted Pfizer a patent covering any drug that blocks this enzyme, meaning that it can sue all of its potential competitors.’1

Luckily, this time they were rebuffed.

Anyhoo, back to the drug. During phase one clinical trials, where humans are given the drug for the first time to see what effects it may have, many of the volunteers were hanging on to their medication, rather than handing them back. This was very unusual. Almost unknown in fact.

When researchers went out to find out why this was happening it was discovered, not quite sure who admitted to this, that sildenafil/Viagra improved erectile function. Thus, Viagra, the first PDE5i, was born. The first drug that worked simply and effectively to improve erectile dysfunction (ED). As for treating angina… that piffling indication was rapidly shelved as the dollar signs appeared in the sky above Pfizer HQ. Sex, as they say, sells.

In truth, it is actually one of the best drugs ever. Not only does is treat ED, but it can also be used by mountaineers to prevent pulmonary oedema (fluid filling up in the lungs), which is one of the major symptoms of altitude sickness. It does this by reducing the blood pressure in the pulmonary vessels (blood vessels in the lungs).

To explain a little further. If you climb very high, and the oxygen level drops, the heart pumps blood harder and harder through the lungs to get as much oxygen as possible into the system. This can result in fluid leaking out of the vessels and into the lung tissue, so they fill up with fluid. At which point you effectively drown, so you die. Viagra stops this happening, by lowering the blood pressure in the lungs.

Unsurprisingly, Viagra is used to treat people who have pulmonary hypertension (high blood pressure in the blood vessels in the lungs) at sea level. It is sold under the name Ravatio, for this indication – but we know that it is just Viagra. In addition, Viagra can be used to treat Raynaud’s disease, where the small blood vessels supplying the fingers and toes constrict, leading to painful cold fingers.

So, here we have a drug that can treat angina, pulmonary hypertension, erectile dysfunction and Raynaud’s disease at the same time. Thus, you can have great sex at twenty thousand feet above sea level, not get chest pain, or breathless, and stay warm at the same time. What more could a man ask for?

How does it do all these things? The answer is that it increases Nitric Oxide (NO) synthesis in endothelial cells. When it does this in the penis, it stimulates erections. In the heart, it opens up coronary arteries. In the lungs, it dilates the blood vessels, in fingers and toes it opens up arteries. So, all of the many different effects, are all due to exactly the same process – increased NO synthesis. Viagra also lowers blood pressure – as you would expect.

At the risk of blowing my own trumpet, I talked about this in my book ‘Doctoring Data,’ under the heading ‘Viagra and the drugs of unintended consequences.’ I posed the question. ‘If we were to prescribe Viagra as an antihypertensive, which is entirely possible, and it were found to reduce the risk of heart disease and stroke, which effect do you think would be responsible for the benefit? The blood pressure lowering effect, or the anticoagulant effects? Or something else.

Since I wrote those words, someone has actually looked at the impact of PDE5is on cardiovascular disease. Researchers at Manchester University, in the UK, studied the use of Viagra in people with diabetes – who often have erectile dysfunction. Here is what they found:

‘Viagra could prevent heart attacks, according to research. Patients taking the male impotence drug were found to have a lower risk of having a heart attack or dying from heart failure than those not on the medication. The lead scientist told the Daily Express the findings are “incredibly exciting”.2

The research paper was published in ‘Heart’, a BMJ journal. Actually, this paper was published last year, but only seems to have hit the press in the last few days. I spotted it in the Times a few days ago.

Here are the main results (for those readers who like their statistics)

‘Results: Compared with non-users, men who are prescribed PDE5is (Viagra, Cialis and the likemy words) (n=1359) experienced lower percentage of deaths during follow-up (19.1% vs 23.8%) and lower risk of all-cause mortality (unadjusted HR=0.69 (95% CI: 0.64 to 0.79); p<0.001)). The reduction in risk of mortality (HR=0.54 (0.36 to 0.80); p=0.002) remained after adjusting for age, estimated glomerular filtration rate, smoking status, prior cerebrovascular accident (CVA) hypertension, prior myocardial infarction (MI), systolic blood pressure, use of statin, metformin, aspirin and β-blocker medication. PDE5i users had lower rates of incident MI (incidence rate ratio (0.62 (0.49 to 0.80), p<0.0001) with lower mortality (25.7% vs 40.1% deaths; age-adjusted HR=0.60 (0.54 to 0.69); p=0.001) compared with non-users within this subgroup.’3

For those who don’t like their statistics quite as much as me (shame on you). I shall attempt to simplify.

  • Over a seven year period, those men taking PDE5is (Viagra Cialis and the like) had a 4.7% reduction in overall mortality – compared to men who did not.
  • Those taking Viagra were 38% less likely to have a myocardial infarction
  • If you did have a myocardial infarction, those who were taking PDE5is had a 25.7% death rate. Those who were not taking PDE5is had a 40.1% death rate. So, if you were unfortunate to have a heart attack, you were 14.6% less likely (absolute risk reduction) to die if you were taking PDE5is.

Or, to shorten this even more

  • 4.7% reduction in overall mortality
  • 38% reduction in MI (relative risk reduction)
  • 14.6% reduction in death after an MI

Whilst the first figure of a 4.7% reduction in overall mortality may not sound terrible exciting, it knocks all antihypertensives and cholesterol lowering medication into a cocked hat. Even if you add them together and multiply by two – on their best day. Because 4.7% is an absolute risk reduction. [Absolute mortality reduction in the Heart Protection Study (HPS), the most positive statin trial, was 1.8% over five years]

The benefits of Viagra are even more startling when it comes to having a heart attack (MI). The current ‘gold standard’ treatment of choice is Primary Percutaneous Coronary Intervention (PCI), which basically means popping a stent into a blocked coronary artery to open it up again.

It has been estimated that PCI results in a 2% absolute reduction in mortality4. On the other hand, Viagra gives you, very nearly, a 15% reduction in overall mortality. Or, to put it another way, Viagra may be seven and a half times as effective as PCI.

But it does not end here. it was also found that men with heart failure were 36% less likely to die if they took a PDE5i.

‘In the other subgroups, there was an inverse association between PDE5i use and all-cause mortality. Those with a recorded history of congestive cardiac failure, TIA and PVD had 36%, 40% and 34% lower risk, respectively.’ [A TIA is a transient Ischaemic attack/small stroke. PVD is peripheral vessel disease.]

Congestive cardiac failure is usually shortened to heart failure. [This 36% is a relative risk reduction, and I could not work out what the absolute risk was from the paper. I am probably too thick].

The effect on heart failure is almost certainly because another benefit of increasing NO is that you increase ‘angiogenesis’, otherwise known as, ‘the creation of new blood vessels’. If a coronary artery does completely block, this often leads to heart failure, as not enough oxygen and other nutrients can get into the heart muscle downstream.

However, if collateral blood vessels develop, the blood will be directed around the blockage and back into the artery downstream, through these newly created blood vessels. Although collateral circulation is not as effective as a fully patent coronary artery, it will create a significant flow of oxygen and nutrients once more. Thus, heart failure will be greatly improved.

Louis Ignarro, who identified nitric oxide (NO) as the key chemical messenger that dilated blood vessels, and won the Nobel Prize for doing so, decided to start treating people who have end stage heart failure with l-arginine. He had been looking for a substance that would, naturally increase NO, and found l-arginine did the job best. He has had some amazing results. Perhaps he should start using Viagra instead.

This study, I must add, was not interventional, it was observational. However, it strongly supports the hypothesis that increasing NO synthesis is just about the most important thing you can do. If you want to avoid dying from CVD.

Do I think everyone should take Viagra? Well, if you have heart failure, diabetes and a high risk of CVD – probably. Will you get a doctor to prescribe it for you, for CVD prevention? Absolutely no chance. Will anyone ever fund a study on this? With the drugs now off patent – no chance.

Oh, the joys of modern medicine. Unless someone does a controlled randomised double blind study on a medication, doctors will not prescribe – are not allowed to prescribe. However, virtually the only people with the money to do such studies are pharmaceutical companies. If the patent life of a drug has expired, no money can be made. So, no trial will be done. So, drugs that are almost certainly beneficial wither on the vine.

Unusually, for me, I do not blame the pharmaceutical companies for this. They are not charities. They need to make money or they die. You cannot expect them to spend hundreds of millions on a clinical study, without any possible means of gaining a return on their investment. We live in a funny old world.

In the meantime, look to other things that can increase NO synthesis. L-arginine/L-citrulline does this. Potassium does this. Sunlight does this. Exercise does this. Meditation does this. Vitamin D does this, as does Vitamin C. What are you waiting for? Go for a walk in the sun and eat an orange – you will live forever.


1: https://www.forbes.com/2002/10/23/cx_mh_1023pfizer.html

2: http://www.independent.co.uk/life-style/health-and-families/health-news/viagra-could-lower-heart-attack-risk-and-risk-of-dying-from-heart-failure-a7082801.html

3: http://heart.bmj.com/content/early/2016/07/26/heartjnl-2015-309223.full

4: https://www.ncbi.nlm.nih.gov/pubmed/12517460?access_num=12517460&link_type=MED&dopt=Abstract

149 thoughts on “What causes heart disease part XXVIII

  1. ellifeld

    Great news! I just happened to be reading a “news alert” that comes to me via the NYTimes, this one about the results of study of the drug Repatha, a PCSK9 inhibitor, with the headlines, “A drug prevents heart attacks in many with no other options left.” “It’s a new ballgame”, one expert said, It’s also $14,523 a year.” by Gina Kolata. The study was paid for by Amgen, maker of the drug. (No problem so far). If you read through the article it seems pretty hard to believe the experts here. Even the numbers in the article are misleading. First of all in one paragraph they use a 20% reduction (this is the figure that is most talked about in the article) in death from heart disease after 2.2 years of use. Next paragraph a 15% reduction in combined rish of HA or stroke. Finally next paragraph, absolute reduction in the risk of HA or stroke was 1.3% at 2 yrs and 2% at 3 yrs. Further down is a statement about 10% taking the drug had a HA or stroke or died of heart disease during the trial. But I guess that’s completely irrelevant because according to Dr. David Maron, director of preventative cardiology at Stanford, “the future looks brighter for patients with established coronary disease.” Gee, it sounds so promising maybe I should wish for coronary disease.

    1. Frederica Huxley

      Yes, I found it hard to believe the pharmaceutical companies wouldn’t take advantage of the potential cardiovascular effects of these off patent drugs – certainly worth tweaking the formula, renaming the drug then doing the required research on the exciting new blockbuster. It’s been done many times before.

      1. John Collis

        Which is what happened with omeprazole being reformulated and rebranded as esomperazole.

      1. ellifeld

        That’s quite an honest analysis compared to the one I read. The NYTimes article stressed what a miracle it was, despite the 10% mortality and only a 1-2% benefit.

      2. Andy S

        Hi Lew: Again, learn to read between the lines.
        Prof Sir Nilesh Samani, the medical director at the British Heart Foundation, said: “This trial is a significant advance. [add] in maintaining to generate huge profits now that the patent on statins has expired

        This is closer to the truth.

      1. ellifeld

        It looks to me the thing that bothered this physician most were not the results, which seem pretty poor to me, roughly 1.5% for HA and 0.4% for stroke reduction (both non fatal), but the costs. And of course this also ignores the downside, which in the article I read roughly 10% of participants had a HA, stroke or died (it’s not clear what % of each and how many actually died). Quickly looking at this I would jump to a conclusion that there is a 1.5% reduction in HA and a possibly larger % that you would have a HA. Same with stroke. And since this drug didn’t prevent death and some did die during the drug trial, well it would seem prudent to avoid it at all costs. Yet somehow this simple analysis is not mentioned. Only something about LDL and costs. Of course that is after much back patting “on the fact that our background medical therapy and interventional techniques are impressive” and “the bad news is that it’s hard for any new therapy to make what is great, greater.” Really? Cholesterol therapy is great?

      2. Andy S

        Hi Ellifeld: Again you have to read between the lines.
        “on the fact that our background medical therapy and interventional techniques are impressive”
        by adding “in generating a ton of money” you get the true meaning.


      My Doctor appointment this morning. “Think about this new drug Repatha, a PCSK9 inhibitor, this is just what you need to stay alive” Give her the brochure on this and let her think about it.
      My cholesterol numbers are medium high but I do not believe in Statins, I have chest pain with in 2 hours of taking any STATIN. The Doctor thinks this product is different. Yea !! Right !!!!

      1. Andy S

        Hi Kathryn LB: I explained to someone on this thread about the different types of cholesterol. The key point is will Repatha lower the bad/bad LDL(sdLDL) cholesterol only or also the good/bad LDL (large fluffy) cholesterol. Your doctor should be able to provide the answer, if not – get one who can. My doctor did not know that low TG was good, developed diabetes and retired. Now I am avoiding doctors.

      1. ellifeld

        That one is worse than what I read, “New drug cuts ‘bad’ cholesterol by 60% on average, reducing heart attack risk”- Headline, but down below, “However, the findings, published in the New England Journal of Medicine, found that the drug had no impact on the rate of cardiovascular mortality” Actually this should be seen as clear evidence that cholesterol is irrelevant in cardiovascular mortality but that doesn’t seem to be the message the experts took from it.

      1. Mr Chris

        Just read on “Seeking Alpha” that investors do not think the results of the trial were that great, and sold the shares down.
        Investors more perspicacious than GPs?
        Now there s a thought

      2. Gary Ogden

        Mr Chris: They have no choice but to have a keen eye for flimflam, as fortunes can be made or lost in the blink of an eye in the world of computerized trading.

  2. cecil

    Great information.
    However the numbering system for your posts is erratic. You have no Part XXII and now you have two different posts called Part XVIII.
    Might I suggest calling this one part XXVIII since the last one you posted was part XXVII? Unless you want to call it part XXII to fill in the missing post.

      1. Andy S

        The viagra study was done on men. Would the therapy also work on females or would they benefit by association with a male taking the drug?

  3. Andy S

    What a relief, I can forget about plaque now that there is viagra. I had so many questions about plaque to look into, felt like being sucked into a black hole. Now I can sleep soundly and not toss and turn all night searching for answers. Thank you viagra. Is there an antidote for overdose?

    1. Mark Johnson

      What a relief, I can forget about plaque now that there is viagra. I had so many questions about plaque to look into, felt like being sucked into a black hole. Now I can sleep soundly and not toss and turn all night searching for answers. Thank you viagra. Is there an antidote for overdose?

      You maybe able to toss, but not sure about turning.

      1. Andy S

        I let nature take it’s course, NO is reduced as we age. NO is excellent for young people with metabolic syndrome. Elderly gentlemen walking around displaying side effects of viagra ?

  4. Maureen H

    This post is wonderful Dr. K. Funny and very very interesting, especially to someone like me anyway as I have IPF and pulmonary hypertension is probably in my future. How great to learn of simple measures that may help. Today is one of the first in a long time that isn’t bitterly cold with freezing blustery winds (Ontario) and as our deck is south facing and sheltered I cleared the snow from it and lay out in my undies, five minutes a side. It is zero degrees but I was toasty. How lovely was that! From now on, as at this latitude the sun is reaching the proper height for Vit D production at noon, I’ll gradually increase the time of exposure. Dr. K., do you happen to know for how long the production of N.O continues after sunning?

  5. Sylvia

    Fanflippintastic. So, as is often said, males living in sunny climes,with citrus dripping of trees, not to mention a drop of vino, are indeed amorous lovers of women, in no need of this help.
    And in Rome recently, for a short break with my sister, we found this to be true, as two matrons were treated so courteously by Italian gentlemen wherever we went.
    Thank you Dr Kendrick for another amazingly good post.

  6. Dr. Göran Sjöberg

    Interesting reading indeed!

    After my MI, 17 years ago, I had a bout of ED, well known to be associated with one of the drugs I immediately was put on, the beta blocker. On the first check up meeting with my “specialist” I brought this issue up. Instantly, without me asking for it, he told me that he was not going to prescribe Viagra to me. Well, after a year I had quit all medication so this issue resolved in a natural manner.

    But what was he “afraid” of?

    And why can a doctor not prescribe a drug which is approved? If you, with CHD, are cheating and claiming an ED-problem can you make him prescribe it to claim the general benefits?

    1. Andy S

      Dr. GS: might be something to do with “Standard of Care”. I am in Canada with “free” access to health care. To control cost there must be guidelines what drugs must be prescribed for each ailment. I have a bit of glaucoma in one eye and could possibly benefit from medical marijuana, but the eye specialist prescribed eye drops instead. Did some research and stopped the drops.

      1. Dr. Göran Sjöberg


        My DT2 wife was diagnosed with glaucoma but with our turn to LCHF her vision problems resolved within one year. Today everything is perfect according to the optometrist. No need for medication.

    2. bobniland

      Dr. Göran Sjöberg: And why can a doctor not prescribe a drug which is approved?

      Off-label prescription likely varies substantially by country and medical guild policy. In the US, I would imagine that any creative male could wrangle a Viagra prescription (although if they don’t already have ED, they may also not have CVD*). That particular dodge doesn’t work so well for females, but if off-label use of PDE5i agents becomes common, they might be able to get it.

      * On another site, a user linked to this old post on the ED & CVD connection:
      It has additional non-prescription tips.

      1. Dr. Göran Sjöberg


        Interesting link!

        I realize that I must be an exception with my severe CVD and at 70 +. My guess is that it might be attributed to the strict LCHF lifestyle since 8 years.

      2. Andy S

        ED & CVD : William Davis figured it out, how can the medical profession apply this finding?
        Here is a suggestion for the cardiologist: Rather than doing ECG, blood pressure, heart scans, stress tes etc t a lot of money could be saved by implementing a simple test – the PST scan (Penis Stiffness Test). The procedures need to be worked out. Medications would not have to be changed.
        Of course the PST test only applies to males, but they need more help than females.

      3. bobniland

        Andy S: William Davis figured it out, how can the medical profession apply this finding?

        Do they want to?

        Based on my read of the history, Dr. Davis had already gone rogue at least 3 years earlier (2004) with his Track Your Plaque book and program (now Cureality), and 4 years later would release the first Wheat Belly book. His next book (Undoctored) is likely to make him even less loved by “the medical profession”.

        ED, interestingly enough, is not a distinct topic in these programs, probably because it’s secondary to the real underlying problem, and addressing that IS a program focus.

        Disclosure: I’m a contributor on the Wheat Belly Blog.

    3. Andy S

      Dr. GS: I am so glad your wife’s glaucoma was resolved. All cells need a healthy blood supply to function properly, cell survival is at stake. HFLC is the answer for healthy blood.

  7. JanB

    That’s gradely, Dr. K. Thank you so much for all your time and dedication. The final paragraph sounded ominously like a final summing up…..and incredibly and hilariously down to earth advice after all the high falluting science we’ve been treated to over the months. IF it is the final part, and I sincerely hope it isn’t, I hope and trust, along with all those that follow your excellent blog, that a book will ensue. I like the idea that you’ve been trying out ideas on us all.
    This afternoon, I heard on radio 4 news that some college or other (I wasn’t listening properly because I was in my studio and had my mind elsewhere) had discovered a drug that will lower cholesterol to ‘record lows’ and thereby save countless lives. I wonder if anyone else following your blog heard this and maybe also my gasp of horror.
    Thanks again.

  8. Eliot

    Perhaps some enterprising drug company can tweak it so it works the same way but they can get a new patent on it. Statins all basically all do the same thing but there have been a few patents granted for them.

    1. Andy S

      Eliot: You have a good idea. The model could be based on the POLYPILL concept. My suggestion would be to add, magnesium,C,E, d3, and a few other secret ingredients. Could you and I patent this idea?

  9. info326vmt

    “Not only does is treat ED, but it can also be used by mountaineers to prevent pulmonary oedema…”

    I always understood it was used by mountaineers when sleeping on ledges to prevent rolling off!


  10. Lee

    So can you buy Viagra or a quality certified generic without prescription? I suffer from Raynaud’s in the winter, so could be worth trialling it next winter. No current problems with the Old Boy but could be something lurking as the fingers & toes only started doing this at 40

    1. Gerard Pinzone (@GerardPinzone)

      Same here. I’ve been taking 5,000 mg of L-Arginine to see if it makes a difference and so far, nada. I’ve never taken a Viagra, so I have no idea if it will help. The trouble is that it’s almost impossible to figure out where to buy it since Googling it results in about a million spammers and seedy websites.

      1. Sylvia

        My niece is going to try cell salt ferrum phos 6x for her reynauds. Very dilute iron, so she will take it for a couple weeks, week off and see.

      2. Drifter

        Yes, it is quite possible. It is OTC in countries like mexico and can be ordered online, although perhaps not legally in some locations. The excelmale site has a whole thread on sources. Searching on ADC or research chemical will yield additional clues.

      3. Andy S

        Gerard : you seem to be a guy who likes to experiment. Be cautious of overdose, permanent erection and no brain. You can’t have everything.
        “Nitric oxide (NO) from iNOS appears to be a key mediator of such glial-induced neuronal death. The high sensitivity of neurons to NO is partly due to NO causing inhibition of respiration, rapid glutamate release from both astrocytes and neurons, and subsequent excitotoxic death of the neurons. NO is a potent inhibitor of mitochondrial respiration, due to reversible binding of NO to cytochrome oxidase in competition with oxygen, resulting in inhibition of energy production and sensitization to hypoxia.”

  11. Jean Humphreys

    Thanks. Sounds like just what I need. Do you think I might get a prescription, if I promise not to sexually assault the postman?

    1. Andy S

      Seriously, if you do take the medication one of the side effects is headache and then there would be no interest in the postman.

  12. mikecawdery

    Cardiology’s annual meeting: There was no benefit from taking the drug, evacetrapib. The drug’s maker, Eli Lilly, stopped the study in October, citing futility, but it was not until Sunday’s meeting that cardiologists first saw the data behind that decision.

    Participants taking the drug saw their LDL levels fall to an average of 55 milligrams per deciliter from 84. Their HDL levels rose to an average of 104 milligram per deciliter from 46. Yet 256 participants had heart attacks, compared with 255 patients in the group who were taking a placebo. Ninety-two patients taking the drug had a stroke, compared with 95 in the placebo group. And 434 people taking the drug died from cardiovascular disease, such as a heart attack or a stroke, compared with 444 participants who were taking a placebo.

    So is LDL bad and HDL good or are both irrelevant?

    1. Andy S

      It is more complicated than that. There is HDL (good cholesterol) which can be subdivided into sdHDL(small dense HDL) or bad/good cholesterol and large fluffy HDL or good/good cholesterol.
      Now LDL is the bad cholesterol, large fluffy LDL is good/bad cholesterol. Small dense sdLDL is the very bad/bad cholesterol. then there is glycated LDL which is bad cholesterol that can turn into really bad oxLDL. There is also awful oxidized sdLDL.
      When drug companies developed evacetrapib, perhaps they mistakenly targeted the wrong good cholesterol. Statins reduce LDL, the problem is that the good/bad cholesterol is reduced and the very bad/bad cholesterol is increased. Your doctor should be able to explain this better than me.

      1. mikecawdery

        Indeed you are right. For example, David Evans in his three books references some 500-700 papers saying the same things. The late Dr. Graveline, Dr Kendrick, Dr, Ravnskov, and others have been writing about this for at least the last decade. Unfortunately the cholesterol gurus simply ignore anything that contradicts the approved medical Gospel.

      2. Mark Johnson

        It is more complicated than that. There is HDL (good cholesterol) which can be subdivided into sdHDL(small dense HDL) or bad/good cholesterol and large fluffy HDL or good/good cholesterol.
        Now LDL is the bad cholesterol, large fluffy LDL is good/bad cholesterol. Small dense sdLDL is the very bad/bad cholesterol. then there is glycated LDL which is bad cholesterol that can turn into really bad oxLDL. There is also awful oxidized sdLDL.
        When drug companies developed evacetrapib, perhaps they mistakenly targeted the wrong good cholesterol. Statins reduce LDL, the problem is that the good/bad cholesterol is reduced and the very bad/bad cholesterol is increased. Your doctor should be able to explain this better than me.

        So what you’re saying is: there’s good cholesterol and bad cholesterol. The good cholesterol sometimes can become bad cholesterol, which I guess is not good. Then sometimes the good bad cholesterol gets even badder and becomes really bad cholesterol, sort of like a panto dame but more menacing. But the kicker is that the bad cholesterol is sometimes not so bad and becomes good, except when it’s bad, or really bad, in which case it’s not good. So overall, the good or bad (or even worse) cholesterol is good or bad depending on whether it’s good, or bad, or even worse.

        When companies developed evacetrapid they didn’t have a clue either and simply targeted a number, not good or bad, just a number. Most doctors don’t have a clue.

      3. Andy S

        GOOD/BAD: yes Mike you understand the problem. We have to spell it out clearly for the average consumer of medicine. Problem is that purveyors of statins educate the doctors and set the “healthy” cholesterol levels. Who will lead the re-education battle?. Understanding GROUPTHINK is essential, google it.

  13. mikecawdery


    New Cholesterol-Lowering Drug Shows Early Promise

    THURSDAY, Oct. 3 (HealthDay News) — An experimental drug that lowers LDL “bad” cholesterol by helping sweep it from the bloodstream appears to be both safe and effective in its first human trial.

    The drug known as ALN-PCS reduced cholesterol an average of 40 percent in the small, early study, and, if proven to work in large trials, potentially could replace or complement statins, the researchers said.

    And a reminder of the WHO-BHF best survival levels for TC:
    Estimated lowest mortality rates for TC blood levels
    All Cause mortality 222 mg/dl 5.75 mmol/L
    Non-communicable disease 210 mg/dl 5.49 mmol/L
    Cardiac Disease 208 mg/dl 5.44 mmol/L

    http://www.heartstats.org/documents/download.asp?nodeib=6797 This URL no longer exists? WHY?
    Now on https://renegadewellness.files.wordpress.com/2011/02/cholesterol-mortality-chart.pdf

    Currently, statin drugs such as Lipitor, Crestor and Zocor are widely used to control cholesterol. One heart doctor not involved with the new study said another class of drugs might be useful.

    The “experts” apparently don not read

    “Cardiovascular disease remains the leading cause of death of men and women globally and reduction of LDL cholesterol with statin medications has been demonstrated to substantially reduce the risk of first or recurrent cardiovascular events,” said Dr. Gregg Fonarow, a professor of cardiology at the University of California, Los Angeles.

    However, while statin therapy is very effective for heart risk reduction and generally well tolerated, a substantial number of people cannot achieve ideal LDL cholesterol levels despite high statin dosing, he said. And others can’t take statins at all.

    “As such there is an important need to develop addition therapies to lower LDL cholesterol,” Fonarow said.

    The new trial demonstrated dramatic reductions in LDL cholesterol on top of statin therapy, he said, and “these agents are being further evaluated in very large randomized controlled clinical outcome trials.”

    The report was published Oct. 3 in the online edition of The Lancet.

    In this early, phase I trial, researchers tried the drug on 32 healthy patients with mild to moderate raised low-density lipoprotein (LDL) cholesterol. Patients were randomly assigned to one of six doses of ALN-PCS or an inactive placebo.

    1. Andy S

      “As such there is an important need to develop addition therapies to lower LDL cholesterol,” Fonarow said.
      When reading scientific literture one must develop the ability to read between the lines. Applying this technique you will at once notice that there is something missing ie “and generate a huge profit for our company”. Now you see how easy it is to fully comprehend motivation of the drug company.

    1. Andy S

      JDPatten: I was searching PDF5 reason for existing when I read the reference in your comment. Our bodies produce PDF5 for a reason. PDF5 inhibitors (viagra) can have wonderful effects, what side effects is one willing to endure. Scientists do not completely understand the functioning of the human body. Is too much NO also bad?

  14. mikecawdery

    ,,,,,,,,,,,,,had a 4.7% reduction in overall mortality

    From the text it would appear that the percentages are relative. These could be highly inflated. I must download the relevant papers and see if the real numbers are published. They should be if HRs are used but often not.

  15. mikecawdery

    Depending on the category they are reporting real rates. For example in post MI the rate is ~4%. This means that over the time period 1 in 25 patients will benefit. This is unlikely odds for the individual diabetic patient post-MI in terms of risk. I would fall into this category; the other benefits might be more attractive.


    Dr K, Great article, just the information I need to increase my NO. I am a Heart Attack survivor and doing great. With this information, I am sure I will do even better. I had a Dr. appointment this morning … my head is still spinning. Statin, Statin is the pill of the day … I said no for the hundredth time. Why do they not get it ???

  17. jerome@jburne.org

    Brilliant Malcolm and hugely entertaining.

    It came just a I was reading abstract of latest two year study on the Evolocumab in NEJM. It is very positive. Having injections for two years means you have (I think) 1.7% lower chance of having a heart attack, stroke, revascularisation etc than those poor buggers who were on a placebo. And your cholesterol will be so absolutely low.

    Would love to repost it on HIUK and make the Evolucomuab comparison. The repurposing old drugs is such a subversive story. Imagine the financial crash if it became widespread.

    Are you still up for writing something for HIUK on the stress cortisol angle?

    Re nitric oxide have you picked up on the research showing that

    a) there are big stores under the skin and

    b) that it is released by the action of sunlight, specifically by the (I think) B rays.

    Suggestion that benefits claimed for vitamin D may actually be due to action of sun on nitric oxide.

    Did a DMail story on it last year.

    Best Jerome

    Best wishes


    Email changing Email changing Email Changing

    My new email is: jerome@jburne.org

    Myzen email being phased out

    Please add to your contacts

    40 Warrington Crescent

    London W9 1EL

    W9 1EL

    0207 286 9294

    07940 393 094

    Blog. HealthInsightUK.org

  18. Reichart

    “In truth, it is actually one of the best drugs ever. Not only does is treat ED, but it can also be used by mountaineers to prevent pulmonary oedema”

    So there are a bunch of mountaineers out there climbing around with erections?

  19. Lew Stalwarter

    Dr Kendrick
    Once again a great article.
    You mention, not for the first time, the benefit of potassium.
    Apart from choosing good dietary sources do you have any advice re types of potassium supplements.

      1. mikecawdery

        There are of course pharmaceuticals such as slow release potassium pills, lo salt as well as bananas. And the NHS even does a test for low potassium. Should not be a problem. Magnesium might be? It is assumed that food contains enough but after decades/centuries of agriculture do plants now get enough Mg?

  20. Roy Butler

    As always another fascinating post also quite entertaining, perhaps one day the truth about CVD will become apparent to everyone especially the medical Luddites. Keep it up Dr Kendrick

    1. Andy S

      Roy: I have read somewhere that in all but a few individuals a person in the medical profession is not able to escape the “Intellectual Black Hole” mentioned in the previous section. It is a terminal affliction. They are immune from changing their beliefs. Just ignore the Luddited.

  21. Peggy Sue

    Funny isn’t it – after months of comments about avoiding doctors and the pills that they push there is a pharmaceutical product that people want to get hold of.
    Before getting too carried away take a sneaky peek at the Summary of Product Characteristics for sildenafil. Enough to dampen enthusiasm a bit!

    1. Andy S

      Soul: you have extrapolated. Viagra cures ( hypoNOemia ) one form of ED 100% with very few male patients complaining. The other ED (endothelial dysfunction) the cause of heart disease is still there. A small step for “viagra”, a big step for “penis”.

  22. David Bailey

    I am curious – do people take Viagra for medical reasons at approximately the same dose as they do for recreational reasons? If so, does that leave them with permanent erections – which could be embarrassing, and make it hard to pee!

    Also, is it possible that those men who took Viagra for recreational reasons were somewhat more frisky than those that didn’t – which might skew the statistics?

  23. Andy S

    “‘If we were to prescribe Viagra as an antihypertensive, which is entirely possible, and it were found to reduce the risk of heart disease and stroke, which effect do you think would be responsible for the benefit? The blood pressure lowering effect, or the anticoagulant effects? Or something else.’
    How long would the blood pressure lowering effect last? I understand that shunting blood to an external organ would produce a pressure drop. Would the pressure reduction continue after the blood is returned to it’s proper place? I imagine this is an easy experiment that could be done at home with a simple blood pressure monitor. A double blind study with many participants is not required.

  24. Mark Johnson

    I’m sure I read somewhere that the number one way to increase NO is by exercising, particularly of the high intensity interval type. The body is so capable of looking after itself if only we nourish and treat it the way it was designed to be nourished and treated.

    Also, when a man goes to the doctor and complains of ED, shouldn’t that sound a BIG KLAXON in the doctor’s brain? In the absence of psychological factors, couldn’t ED be the early sign of something more serious a bit further in time? If blood flow is compromised in the nether regions, isn’t it also compromised in areas not quite so visibly obvious?

    1. Andy S

      Mark: I agree with exercise and diet as the way to increase NO.
      The doctor problem could be explained this way: Have you ever noticed the prescription pad on the doctor’s desk? You mention a symptom and the doctor has given you a prescription in 5 seconds or less, this is a conditioned automatic response bypassing the brain. Remember Pavlov and the dogs? sound a bell and gastric juices start to flow.
      The solution might be to ask the doctor to give you a prescription next week when he has had time to reflect on what could be ailing you.

  25. Dr. Göran Sjöberg

    Relating to the present subject I cannot refrain from linking to the newsletter I received today from Dr. Mercola which is about the dangers with testosteron supplements. As Malcom he advocates natural “remedies” when you as a male feels that the years take their toll.


  26. Mark Johnson

    Fasting – Probably the best and most natural way to hugely boost Human Growth Hormone (HGH) and testosterone.

    Increase muscle mass, bone density, skin thickness, libido, improve insulin sensitivity etc. Anti-aging, no drugs necessary.

    1. Andy S

      Hi Mark J: In total agreement with you on fasting, seems it will be the new craze among do-it-yourselfers. This is what is referred to by doctors as “lifestyle” changes, except that they cannot specify what they are. The problem is that a lot of effort is required, whereas a pill is easy to swallow.

  27. John Barr

    So taking a vastly expensive medication, which reduces your LDL by lots, and increases your HDL by even bigger lots, results in more heart attacks than those poor people taking a placebo.
    As a GP, I wonder how many more of these results we have to get before someone has the guts to say that lipids/cholesterol appears to have very little do with cardiac disease. I presume this will never happen as the great and the good can never be seen to be wrong

    1. Andy S

      I can have fun without the medication. Quality of life for people with restricted arteries will improve but they already have heart disease. The fun part will make the patient forget about his heart disease.

      1. JDPatten

        Simple rigidity due to outside influence doesn’t necessarily confer the ability to have “fun”. It’s more complex than that.

    2. Andy S

      One reason might be due to a phenomenon called GROUPTHINK where intelligent people can make bad decisions by not speaking up. Agreeing in order to get along with a group is a cause. Critical thinking is not tolerated in some groups.

    3. Stephen T

      Dr, I’ve read that statins generate $40 billion a year for the pharmaceutical industry. That’s a lot of reasons to keep promoting the cholesterol con. Sadly, patients can’t rely on NICE to protect them and following the guidelines is probably the safe course for GPs.

      I now refuse to attend all routine checks or screening, seemingly designed so they can find a drug or test to give me on the specious grounds of ‘prevention’. Health care is to a large extent a health industry, generating work and customers for pharma. There are lots of good people doing their best, but they don’t write the guidelines.

      1. Andy S

        Hi Stephen: In Ontario Canada a doctor’s income is generated by billing OHIP (government). The doctor has to pay rent, staff etc.. He has to generate income. On a slow day my GP calls me to have some test done with referral to a specialist, so far prostate and thyroid. Nothing wrong with the prostate, thyroid has nodules, cholesterol is above guidelines. Better screening results in more business, that is life.

    1. Andy S

      Hi Gary O: My initial reaction was the same, but now after some deliberation I am not so sure. The limp bird received a direct hit, the other bird is still there.

  28. Ari Manor


    “Or, to shorten this even more
    • 4.7% (and not 7%) reduction in overall mortality
    • 38% reduction in MI (relative risk reduction)
    • 14.6% (and not 6%) reduction in death after an MI”

  29. Håkan

    So, if sunshine and exercise is hard to get in sufficient quantities, as for my old father, then what is the best way to stimulate NO synthesis?

    1. Andy S

      As an old father and a grandfather my source of NO is leafy greens which I grow and juice, and lots of bacon. Supplement with d3 to offset lack of sunshine. If possible send him south for a winter vacation, 4 weeks should be plenty to revitalize him.

  30. Sue Knight

    Hello again Dr. Kendrick,
    As always, a dynamite blog from you. I have just come home from a free CVD risk check up, which I thought a good plan even though I know I’m at low risk (thank the heavens and my careful lifestyle). Although my readings were good, I was picked up on my LDL being too high at 6.04mmols. Other than that I was told I have the heart of a 56 year old (I’m aged 24 … only kidding, I’m 58). Because my LDL is >5mmol they suggested I see my GP; I can feel a statin prescription looming. I have just finished reading Patrick McKeown’s “The Oxygen Advantage”, which describes how to get Nitric Oxide all by yourself, via breathing properly. AKA the Buteyko technique. All very exciting. So I will be saying a big NO to statins.
    Thanks so much your blogs. It is SO good to have you on the planet.

    1. Andy S

      Hi Sue: I looked into Buteyko as well, breathing properly has benefits.If your GP pushes statins ask the following questions:
      -will sdLDL be increased (the good/bad cholesterol classification was covered yesterday
      – will Q10 be reduced
      – will K2 be reduced
      -will bone derived stem cell function be compromised
      -what will be effect on muscle and tendons
      This is a starting list of questions. Suggest GP provide a list of benefits.

    1. Eliot

      Boy, talk about evidence-based conclusions – NOT.

      I wonder if it could be that their gut microbes are finely tuned to their diet?

    2. Andy S

      Hi PaulG: “The fact that they have the best indicators of cardiovascular health ever reported is the exact opposite to many recent suggestions that carbohydrates are unhealthy.”
      The professor could easily prove health benefits of carbs by a mouse study. Feed 2 groups of mice a high carb diet, one group will be restricted to sit on a couch and the other group will be forced to exercise continuously during waking hours.

  31. Jim Chinnis

    While I can’t blame Pharma for not wanting to fund a study on sildenafil, I can and do blame the governments of the world.

    Though I am skeptical re the size of the benefits on mortality and health. Reverse causality is likely a big factor here. Those who still enjoy sex are probably healthier than those who don’t!

    1. Andy S

      Hi Jim C: The question -is more NO better? NO can be measured. Looked at a study yesterday, people with diabetes have higher NO level. To sell a drug the criteria is that raising or lowering some number is beneficial. Sildenafil by itself is not marketable to the general population. I suspect Pharma knows that pushing sildenafil could be a disaster.
      Does sex induced by sildenafil cure CVD?

  32. dearieme

    “Unusually, for me, I do not blame the pharmaceutical companies for this.” Neither do I; you might almost think that such research is the sort of thing an NHS is for.

  33. Mark Johnson

    So, if sunshine and exercise is hard to get in sufficient quantities, as for my old father, then what is the best way to stimulate NO synthesis?

    Arginine / Citrulline powder dissolved in water (look on body building sites / Amazon) Beetroot juice.

    I have a feeling though, that putting an elderly person on a suitable sunbed for 10-20 minutes a couple of times a week is likely to be better for them then all of the blood pressure meds, PPIs etc that they’re likely to be on. No evidence for this just an educated hunch.

    And after they’ve sunned themselves, a session in an IR sauna.

    1. Andy S

      Mark J: agree with your prescription. Sauna is excellent suggestion, in a way it would simulate being in a warm climate. The point is that benefits can be achieved at any age.

    1. Craig

      “a similar study done in Sweden. ”

      Amazing results!

      I’m really sorry now that I deleted all that Viagra spam over the years.

    2. Andy S

      Hi Wab: The astounding part to me is that there is a better and cheaper way to test for NO efficacy.Their “take home” message “Since treatment for ED is associated with confounding by indication, meaning that healthier men are more likely to get treatment for ED, our results should be interpreted cautiously.”
      To reduce confounding I would recommend they do another study using mice, male and female.
      GROUP #1, 50/50 male and female, same age, eating the standard low fat diet with plenty of heart healthy soybean oil
      GROUP #2, 50/50 male and female, same age but eating their natural diet
      After one year give 50% of group 1&2 a daily dose of viagra, then wait until all the mice in both groups die. Two questions will be answered: does viagra work for women and effect of diet+viagra

      1. Andy S

        Some might question why the penis was ignored, by using mice this is not a big deal.

        – endothelial dysfunction + NO = increased blood flow to all organs, therefore good for men and women
        Question is: what is effect of increasing NO by drugs in person with healthy endothelium.
        How to fix dysfunctional endothelium?

      2. Wab Mester (@wabmester)

        Andy, the patients used two different ED drugs. One was a vasodilator, and it had no effect on mortality. Only Viagra had an effect.

        Not perfect, but that reduces that particular confounder.

        As far as astounding goes, the apparent dose-dependent effect is what floored me.

    3. chris c

      Wow! Huge HRs!

      This blows statins off completely, and makes PCSK9s look limp.

      You’d think the manufacturers would be bending over backwards to have these inserted into the Over The Counter list.

      That way they could be slipped in by the back door.

      Have a good holiday. Where are you going, around the world?

      OK OK I’m done.

  34. Dr. Göran Sjöberg

    This very Sunday morning, “doing my homework” in the field of the molecular biology of our cells, realizing its complexity, it is so obvious to me that by attacking whatever specific part of our metabolic chains with a drug we can impossibly see all the collateral consequences of applying that drug. Though the logic involved, e.g. the importance of the cholesterol in our physiology and the statin interference, is still there for you to ponder.

    Then you will most probably also notice all the pharmaceutical windmills which are to be fought if you want to improve on the state of affaires in the medical field. I though wonder about medical professionals like Dr. Kendrick or Prof. Seyfried, who clearly see all this, are able to continue their fight against the obvious insanity of the present state of our health care system without losing hope.

    1. Andy S

      Dr. GS: We give hope to Dr.K by participating in these discussion. I believe the present system will implode when a critical mass of informed people has been reached.

      1. Mr Chris

        A Man
        I wonder too how he knows that-
        Is L-arginine the indirect cause of gout?
        Ideas anyone?

      2. Mark Rand

        Chris gout is first and by far foremost an excretion/secretion problem in the kidney. Many transporters involved and some of those same urate transporters are also present in the synovial fluid in joints, higher in some such as the toe.

    1. Gary Ogden

      brian griffin: The Swedish study said the benefit was dose dependent. They didn’t give the dose, but what I think they meant was number of prescriptions. Five gave a greater benefit than fewer than five.

      1. brian griffin

        Thanks for that Gary. Yes I did see that much but that’s still pretty vague, having no idea of what the definition of a prescription is in terms of strength and number of tablets. Guess I’ll just take one a day and let the wife cope with the consequences! (Just kidding darling.)

      2. Gary Ogden

        brian griffin: My take is that they meant there was a greater benefit for those taking it for a longer period of time.

    2. Andy S

      brian griffin: is there a particular benefit you are interested in?
      Now seriously: increased NO = increased blood flow, therefore probably beneficial at any level of dose and frequency. Blood flow can also increased by stenting, heart transplant and heart bypass operations. The problem is that these procedures could be called a cure but do not fix the underlying cause.

  35. Dave Palliser

    Hello Dr. Kendrick Please can you tell me why after taking viagra I have a nagging but low intensity headache the following day?

    I hope you can help

    Kind regards David Palliser

    PS I love your blogs / posts regarding ” What causes heart disease

    Sent from my Samsung device

  36. Steve

    Should be obvious by now, the powers that be want us to live short lives! Have been taking Citrulline on and off, along with regular vitamins and larger doses of Vitamin C, up to 20 grams when feeling off, around 5-7 grams per day on average. Have looked into ways to reverse fibrin buildup (blood clots) and it appears that Serrapeptase does the trick, adding this to my monthly cycles, maybe a month or two per year. ANY thoughts on that one?
    To keep the aging at bay, Resveratrol, D3, K2, C, Magnes, Zinc, Potas, B multi, Berberine (instead of Metformin) etc. calcium Scan is Zero! So at 56 years young I have no fear of heart issues (wife is a vascular ultrasound tech who scans me every couple years…no issues seen). Give blood 3-4 times per year to dump iron, otherwise add IP6. My other targets are cancer and alzheimers. Eating clean, lowering carbs, zero sugar, filtering water, took up hiking! Adding Retin A to my age spots and Keratosis from years of surfing, seeing nice improvements, and looking 10 years younger…maybe more! Pushing weights at least once per week for all muscle groups, starting on HIT workouts next. Reducing meat and extraneous protein to balance M-Tor, any thoughts on that? everything seem on a J-curve, should keep balanced, veer left or right and age faster, heart problems, etc. Just read that trying to improve telomeres too much may lead to Cancer, another J-Curve!

    Cholesterol is good for optimal health 240-260! A1C, all other measures within the ranges.

    anything I am missing?

    Thanks so much for your commitment to real science and asking questions.

    1. Andy S

      Hi Steve: You are doing much more than I am.
      You did not mention intermittent fasting. Positive effect would be to give cells time to rest and re-juvinate.
      There are studies that show that cancer is related to the cytoplasm, not the nucleus. Therefore look after your mitochondria. I am convinced that all diseases begin at the cellular level. Blood glucose/insulin is the biggest problem. Excess protein = higher glucose.
      Can’t remember why there was a warning to avoid aluminum pots and pans.

      1. Mr Chris

        Andy S
        For aluminium pots and pans, there was a time when aluminium was associated with the amyloid plaques seen in the brains of Alzheimer sufferers. I think this is now discounted as a cause.

      2. Gary Ogden

        Andy S: Aluminum is highly neurotoxic. There was recently a conference in Vancouver, BC, Canada, a biennial affair, of aluminum toxicity researchers. The French scientist who discovered the link between Al in deodorant and breast cancer spoke, as well as researchers studying the link between the Al burden from vaccines and serious adverse events, including the French researcher who discovered the link between vaccination and GBS. The smaller the particles and the lower the dose, the greater the effect.

  37. Dr. Göran Sjöberg

    These links between the NO production and drugs seem to be straightforward.

    What is more intriguing for me is the long term aspects involved and especially those that involve our immune system which seems to be an important integral part of the etiology of CVD and leading to the beneficial/detrimental (?) inflammatory responses in our arteries.

    Now I am reading the chapter “The Innate and Adaptive Immune Systems”, the final chapter in my molecular biology of the cell and with utter amazement about how we can ward off external pathogenic attacks. What a marvelous immune system we have where we understand so much of the molecular biology mechanisms involved but so little about the specifics of different ailments.

    1. Gary Ogden

      Dr. Göran Sjöberg: An amazing system, indeed, the immune system. What fascinates me is the emerging understanding of host-microbe interaction, and microbe-microbe interaction in their effects on this system; I suspect many of the answers to what causes different ailments lie here.

    2. Andy S

      Hi Dr.GS: biology is very very complex with many permutations and combinations of thousands of proteins. To avoid getting bogged down and becoming immobilized by the science one may have to step back and look at health problems from a different perspective.
      The blood supply to a cell determines the health of the cell. What is in the blood that helps or hurts the cell? Lack of nutrients, excess glucose, too far from blood supply, etc. will stress the cell. The cell will communicate and call for help from the immune system. Internally the cell copes the best it can.
      Recommendations for people seeking health advice need not be too scientific. The researchers can study the problems ad infinitum.

  38. turnerjp

    What about maca? Do all purported aphrodisiacs show some degree of Nitric oxide production boosting?

    So, Doctors need to ask permission from politicians to actually help their patients? Well, that sounds like “patients” is an euphemism for “politicians pets”. But we can all be happy about being lower than slaves, because we gave politicians so much power only to protect us from that horrible, nasty quackery. Thanks Molock, politicians also protect us from the greenhouse effect, water pollution, ionizing radiation and mongol invasions.

    And let’s not forget, that if it weren’t for our overlords who care so much for us, no one would know how to read. All hail modern democracy, that saved us from tyranny.


  39. Vlad

    How about the nitric oxide present in tobacco smoke? I mean, real tobacco, pipes and cigars, not junk found in supermarket cigarettes. US Surgeon General studies from the landmark 1964 report found no associations between disease (excepts perhaps to oral cancer) and cigar/pipe smoking. In the UK pipe tobacco was advertised on TV into the 1980s.

    In the current anti-smoking mania I don’t expect anyone to study this. But do you think it’s a coincidence many geniuses from Einstein to Bertrand Russell have smoked and lived with their brains functioning very well into old age?


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