What causes heart disease part XXXIII

29th July 2017

Viagra…. again

When I began this long and winding series on cardiovascular disease (CVD) I already knew a few things that I thought were critically important to the processes underlying CVD.

The first was that, in order to get atherosclerotic plaques started, you needed to damage the endothelium in some way [the endothelium being the layer of cells lining blood vessels]. The second was that blood clot formation was the next key event – thrombogenesis.

Therefore, if you could protect the endothelium and/or stop blood clots from forming, you would most likely see some significant benefits on the risk of CVD. Mainstream medicine is fully in agreement that drugs that reduce the risk of blood clotting will usually have some benefit on CVD risk. Drugs such as aspirin and Clopidogrel – and suchlike.

In addition, most of the acute management of strokes and heart attacks is focussed on getting rid of the blood clot causing the acute event. We have clot busters and stents and other interventions to remove, squash, blow apart and bypass the clot. I often describe interventional cardiologists as ‘blood clot managers’ – obviously not to their faces. They like to think it is all far more cleverer than that.

In short, the importance of blood clotting in CVD is beyond any dispute. Which is why CVD sometimes sits under the umbrella term of ‘atherothrombosis.’

However, the role of the endothelium garners far less attention. If it is ever mentioned, it is towards the end of the process of atherosclerotic plaque development, where it has been noted that in advanced plaques the endothelium is often completely missing. Or if not missing, significantly dysfunctional.

The reason for this, never openly stated, is that to promote the idea that atherosclerotic plaques start with endothelial dysfunction, completely undermines the cholesterol hypothesis. The current hypothesis is that low density lipoprotein (LDL) a.k.a. ‘bad cholesterol’ leaks past/through the endothelium, and into the arterial wall behind.

This in turn triggers the inflammatory processes that creates the plaque (I am paraphrasing madly here). Once the plaque has grown to sufficient size, the overlying endothelium is: weakened, damaged, dysfunctional – choose the word you like best, or add your own. This, in turn makes it more likely that a blood clot will form, as a dysfunctional endothelium no longer represent a powerful anti-coagulant surface, which in my mind I like to think of as a brand new ‘Teflon non-stick frying pan.’

However, if you believe that endothelial dysfunction is the first step, then an entirely different process opens. One that goes like this: The endothelium is damaged/dysfunctional, so a clot forms at that point. The clot is then drawn into the arterial wall and becomes the core of an atherosclerotic plaque which can then grow through repeated blood clots forming at the same point.

This, as I think I have explained many times, fits all the observed phenomena far better than the current cholesterol hypothesis. However, it does knock LDL off its perch as the key factor causing CVD. It can only have a bit part, amongst many other players, in this particular game.

Currently whilst all other conjectures on CVD are allowed to change shape, and swirl around in a massive multifactorial dance, one idea lies beyond challenge, which is that LDL is the conductor, the key player, the factor without which nothing else happens:

Three Rings for the Elven-kings under the sky,
Seven for the Dwarf-lords in their halls of stone,
Nine for Mortal Men doomed to die,
LDL for the Dark Lord on his dark throne
In the Land of Mordor where the Shadows lie.
LDL to rule them all, LDL to find them,
LDL to bring them all and in the darkness bind them
In the Land of Mordor where the Shadows lie.


Or something of the sort.

Currently, it is certainly true that the dark lord rules Mordor, and the ever-seeing eye seeks out all those who criticise the cholesterol hypothesis. Here, for example, is a recent missive from Mordor:

Statin Denial: An Internet-Driven Cult With Deadly Consequences (Editorial JAMA 25th July 2017)

‘We are losing the battle for the hearts and minds of our patients to websites developed by people with little or no scientific expertise, who often peddle ‘natural’ or ‘drug-free’ remedies for elevated cholesterol levels,” adds Steven Nissen. This “Internet-driven cult” denies statins’ benefits and whips up fears of side effects, then profits from the resulting confusion by peddling snake oil.’1

I think I need to shout ‘House’ at this point. Nissen has manage to get in the full set of insults. ‘Denier’, ‘cult’, ‘deadly’, ‘whips up’, ‘fears’, ‘profit from selling snake oil’. What’s missing. Mass murderers…child killers.

Would this be the same Steven Nissen who stated the following, when the new cholesterol guidelines came out in 2013:

“The science was never there for the LDL targets.’ He said. ‘Past committees made them up out of thin air.’ He added.”2 Make your mind up Steven. Either there should be LDL targets or not.

Where was I. Oh yes, just explaining that anyone who dares criticize the cholesterol hypothesis – which is basically interchangeable with statin worship – can find themselves under significant attack. As you can imagine, those working in mainstream research are going to make sure they never do such a silly thing. Grants have a nasty habit of drying up. Tenure can be whipped from under your feet at any time. Do not attract the interest of the ever-seeing eye, my precious.

However, facts have this nasty habit of coming along that cannot be fitted within the LDL hypothesis, and are completely supportive of the ‘endothelial damage/clotting’ hypothesis. A few blogs ago I wrote of a study demonstrating that men with diabetes, who used Viagra, or other PDE5 inhibitors e.g. Cialis, were far less likely to die from CVD.

We know that Viagra/sildenafil has, as a primary mode of action, increasing nitric oxide synthesis in endothelial cells. This is how it maintains erections in erectile dysfunction. It also reduces blood pressure, particularly reducing blood pressure in the lungs. Nitric oxide is also the most powerful anti-coagulant agent known to man. Furthermore, it protects the endothelium from damage, and stimulates the production of endothelial progenitor cells in the bone marrow.

What effect does it have on LDL? None.

What effect does it have on cardiovascular and overall mortality? Well, very recently I was sent this paper: ‘Association between treatment for erectile dysfunction and death or cardiovascular outcomes after myocardial infarction.’

This was a study on over forty-three thousand men over a six-year period, who had previously had a myocardial infarction (MI). Just over forty thousand did not have medication dispensed for erectile dysfunction (ED) (40,077), three thousand did (3,068). They were split into three groups: lowest number of ED scripts, medium and highest number.3

For the sake of brevity here I am just looking at the highest script group.



Well, well, well. Perhaps a couple of other well, wells for luck.

Yes, this study was observational. Yes, this means that other factors that may be at play. For example, those men requesting Viagra and other PDE5 inhibitors, may have been healthier than those who did not. But it is hard to believe they were over five times as healthy. The simple fact is that, when you see an effect as massive as this, it can generally be considered that you are looking at a causal relationship.

To put it another way, this is 81% relative risk reduction in overall mortality. Compare this with statins, in secondary prevention (using best figures possible), statins achieved a 15% relative risk reduction in overall mortality. But statins lower cholesterol levels…right? That is how they work…right? So, LDL does have an impact?

Well, it is of course true that statins lower the LDL level. However, they also do some other things as well. Now, in general I am not a great fan of animal studies. However, I am just presenting one study, done on atorvastatin, looking at the impact on many factors (including NO synthesis) that have nothing whatsoever to do with LDL lowering.

The study was called:

Atorvastatin enhanced nitric oxide release and reduced blood pressure, nitroxidative stress and RANTES levels in hypertensive rats with diabetes.’

A quick summary:

  • Atorvastatin had no effect on blood glucose or cholesterol levels
  • Blood pressure was reduced by 21% (in diabetic rats)
  • RANTES levels were reduced by 50% (RANTES is a ‘chemokine’ associated with endothelial damage)
  • Nitric Oxide (NO) was increased
  • ONOO (peroxynitrate) was decreased. (ONOO is a potent inhibitor of NO).

Summary: ‘These findings provide insights into mechanisms of restoration of endothelial function and vascular protection by atorvastatin in diabetes and hypertension.’ 4

When statins first emerged, they swept all before them. Included the discussion on what causes CVD. Cholesterol skeptics, such as, Professor Michael Oliver, were completely bowled over, and admitted they had been wrong, when statins were shown to lower CVD risk (the true magnitude of the benefits was massively over-hyped, but that is a discussion for another day).

Statins were designed to lower LDL/cholesterol and lower CVD risk and they did. End of argument.

Well, perhaps not quite.

If you decide to look more closely at the process of CVD, and more closely as the actions of statins, a different picture emerges. One which fully supports endothelial damage as the first step in plaque formation. Because statins do many more things than LDL lowering. It could be said that statins are simply the poor man’s Viagra (other PDE5 inhibitors are available).


1: http://www.latimes.com/science/sciencenow/la-sci-sn-statin-denial-20170724-story.html

2: http://www.nytimes.com/2013/11/13/health/new-guidelines-redefine-use-of-statins.html

3: https://www.ncbi.nlm.nih.gov/pubmed/14692706

4: https://www.ncbi.nlm.nih.gov/pubmed/25716966

266 thoughts on “What causes heart disease part XXXIII

  1. regina wynn

    I showed my lipid clinic doctor your book ‘the cholesterol con’. He did not like it and challenged me with arguments such as ‘how can the many be wrong and a handful of others right? He is the CON because he makes money from selling his books. I do not take any money from anybody!” I know it is my choice who to believe but I also feel that an act of faith is precisely that and in the meantime I am concerned about my future health and quality of life….

    1. Antony Sanderson


      The argument “‘how can the many be wrong and a handful of others right?” is not an argument. What it says to me is that we have a lazy person who cannot be bothered to look at the arguments and is prepared for others to do the thinking for him.

      It may be that he is frustrated/guilty/angry knowing, deep down, that he is not making the effort. As my doctor said to me when I brought up statins and the research on associations with interstitial lung disease . . . “We do not have the time to do the sort of research you are doing”.

      1. Craig E

        Antony this has been exactly my experience too. I wrote a reference laden one pager to my Mother’s doc about statins/cholesterol and she said she didn’t have time to look into it. Imagine if you went to an accountant who ‘didn’t have time’ to keep abreast of changing tax laws…or a defence lawyer who ‘didn’t have time’ to keep across changes to the law!

    2. Stephen T

      Regina, your doctor clearly doesn’t know much about the history of medicine. Today’s orthodoxy is yesterday’s folly.

      1. norahpower

        … and yesterday’s orthodoxy is today’s folly: “In a startling reversal of accepted medical practice, experts writing in the British Medical Journal (BMJ) on Thursday said the traditional “complete the course” message designed to avoid antibiotic resistance should be discarded.” This appeared in the Irish Times last week.

    3. David Bailey


      I think you should point out to him that all Dr Kendrick’s books are carefully referenced – showing exactly where the data came from. I think this is the important point – over and over again, a study says one thing, and the medical advice says something quite different!

  2. csbarclay2410

    The ‘One Ring’ rhyme was written by a certain Oxford professor. That is of course just an association.

  3. Bill In Oz

    Thank you Dr Kendrick for this post. It is illuminating. I have an appointment with my GP for next Tuesday, the 2nd. I had already decided to request Viagra. Now I will go with a print out of your post today. And if it arrives in time from Amazon, a copy of your earlier book on Cholesterol.

    Some additional notes : There is a post by PD Mangan that discusses how Viagra is more effective for CVD than statins. See here : http://roguehealthandfitness.com/viagra-potent-heart-disease-drug/

    Also there is a formulation of Viagra available as part of our Australian Pharmaceutical Benefits Scheme. ( PBS ) for CVD. I checked & discovered this after reading Mangan’s post. It’s a lower strength dose. I suspect the PBS and our government, does not want to encourage & subsidise Australians with heart disease, to also indulge in sex. 🙂

    ( There is an element of purient puritanism in our conservative government here. But that is another subject. )
    Unfortunately Mangan is not a medical doctor. And his ‘research’ is not recognised as such by the medical powers that be here.

    But you are a medical doctor, Dr Kendrick. And as my GP is also from the UK ( English who migrated here in the 1980’s ) there is a chance he will listen to your remarks here. I will let you know.

    Maybe this will open his mind a tad.

    Again my thanks !

    1. Craig E

      Hi Bill maybe we need to use the evidence to get satans er I mean statins OFF the PBS given how useless they are. I wonder how much of our taxpayer dollars goes to subsidising them?

      1. Bill In Oz

        Probably billions of dollars. But I have no ideas about how to get them delisted from the PBS

    2. Bill In Oz

      Following up : Unfortunately the information I provided did not open up his thinking at all. Viagra he considers an old drug from the 90’s which has been replaced by statins.

      Again we had the discussion about him wanting me on statins and me declining and citing your book Dr Kendrick. He had no reply for that.
      However he checked my blood pressure and as it was high prescribed a drug called Irbesartan (75 mg) to reduce my blood pressure.As it is of the ACE related type I have agreed to take this..But I notice that potassium supplements are expressly not allowed while taking this drug. Bugger I have ordered some from Iherb.

      Last night I analysed my blood test results for the past 10 months. An interesting pattern emerged. After having chest pain I was referred to a cardiologist last September. The chest pain was due to anemia due to aspirin which I took for longevity purposes. I discontinued the aspirin and the chest pain went away after a blood transfusion.
      But meanwhile on September 20th the cardiologist put me on statins ( Crestor). My total Cholesterol was 5.1 nmol. with triglycerides at 1.3 and HDL-C at 1. LDL-C was 3.5. Knowing nothing I took them. But looking back it is clear that this was a pretty good report. Bloody obvious there was no need for a statin script at all.

      After taking the statins things went very much awry ! On 24/2/17 Total cholesterol was 4.5. But Triglycerides rose to 1.8 nmol and HLL-C fell to just 0.9 nmol ( LDL-C was just 2.8 which is listed as high ! ) But things were Crook in Tallarook ! And the chest pain had also returned as a low level constant thing.

      By this stage I had got myself informed on statins and stopped taking them. The Cardiologist when I told him sacked me. No bloody loss at all I think. Arrogant prick.

      I had follow up blood tests on the 1/5/17. after 11 weeks with no statins. This results were as follows : Total Chlesterol 6.7 nmol; Trigylcerides 1.6 ( Hurray dropping ! ) HDL-C 1.3 ( Hurray rising ! ) LDL -C 4.7 nmol. My GP complained about LDL-C going up and I commented on the others going down.

      More blood test this week : the pattern continues : Total cholesterol 6.2 nmol.( dropping ) Triglycerides 1.9 nmol ( up 0.3 ) HDL-C 1.2 nmol ( drop of 0.1 ) And finally LDL-C 4.1 nmol ( a fall of 0.6 ).

      All of this without any statins at all.

      But I may start taking Niacin again. I was doin for 3 months ( March till ) June) It helps increase HDL-C and lower Triglycerides. I ran out a month ago. It’s cheap and an over the counter supplement.

      1. chris c

        Seen this?


        The sterling work done by Dave Feldman is on his own site


        Absolutely fascinating and appears to be “new to science” unless anyone knows different – admittedly he is one a of a special case of “hyperresponders” so the rapid changes in LDL may not be so prevalent in us lesser mortals – or they might just be happening out of sight of the usual tests.

        Either way another spanner is thrown into the “cholesterol hypothesis” – something highly dynamic is measured once and results in lifetime medication, on a different day it might be “normal”.

        Two reasons I think this is highly important

        1) it is highly important

        2) the venom and bile with which he is being spewed by the Followers Of Conventional Wisdom

  4. Malcolm Lewis

    Dear Dr Kendrick,I have just read your last e-mail on the unexpected effects of viagra. I am 67 and have no erectile problems, do I have to take viagra to extend my life ? I am sure that you will be trying to research this further. Also should I continue to resist my doctor’s advice to start on statins, I have no heart problems just slightly high blood pressure. Thank you for your e- mails Malcolm Lewis

    1. David Bailey

      I know Dr Kendrick is wary of answering any question which might be described as a request for medical advice over the internet for legal reasons.

      My position is much the same as yours, except that I did accept statins at age 60 – indeed, I was quite eager to do so because I thought of them as life extending pills! It took 3 years before I got severe muscle cramps, and it took some time to track this down to the statins because I had been taking them for so long, and the side effects typically show in the first month or two. Also, the symptoms seemed too extreme to correspond to the ‘muscle pains’ described in the patient information leaflet!

      I recovered completely after stopping the statins, but be warned, some people here and elsewhere report that they never fully recovered from the side effects. Personally, I’d definitely not take statins under any circumstances. I try to take as few drugs as possible now (just blood pressure tablets) so I don’t plan to take viagra.

      1. Mr Chris

        David Bailey
        It took me two years to get over statin side effects.
        I take no medicines long term. For blood pressure, exercise, beetroot?

      2. Mr Chris

        Hello Jane,
        It is starting to creep up towards what a Dutch site, said is right for my age.
        I buy cooked beetroot and mash them up in the mixer.
        Someone suggested mixing beetroot juice with apple juice which I intend to try.

    2. Stephen T

      Malcolm, in your situation there is no benefit but you have the full risk of all the known adverse effects, such as memory loss. According to an article by Dr Malcolm Porter, The Times medical correspondent, a good mediterreanean type diet is five times more effective than statins. He estimated that you need 400 people to take statins for one person to benefit slightly. What about the side efects for the 399?

      The guidelines are heavily influenced by pharma and your doctor is just repeating what they say.

      1. Socratic Dog

        Worth mentioning that the “Mediterranean Diet” mantra was popularized by a certain Dr Ancel Keys. That gives me pause.

      2. Mr Chris

        Socratic dog,
        We are all going to be OK because I see there is a suggestion that all men over 60, and women over 75 should be on statins, and not even moderate drinking allowed, since even light drinking does for your heart.

      3. chris c

        If they were trying to make us all ill they couldn’t be doing it much better.

        Everything I have found that improves my health is pretty much the exact opposite of what I was told to do. N=thousands.

      4. Gary Ogden

        chris c: I couldn’t agree more. Yesterday I sent in the survey by the doctor group. I always give my GP top marks because she’s really good. One of the questions was “How do you rate your health,” with the choices from excellent to crap. I checked excellent, and wrote in next to it “Because I usually do the opposite of medical advice.” Another question was about mental health. No doubt because they have all the latest drugs for that!

      5. chris c

        Hahahaha they’ll diagnose you with a Personality Disorder after that reply!

        Yes I have the distinct impression that good doctors are being held back as much as poor doctors are being aided by The Guidelines.

        Somewhere I read a sarcastic article about the patient who’d fallen and thought he might have broken his wrist. First the doctor checked his blood pressure and prescribed medication. Then he requested a lipid panel. Then he asked a bunch of questions off a checklist on The Computer.

        “Aren’t you going to examine my wrist?”

        “Sorry, your appointment is now out of time. You’ll have to make another one to have your wrist looked at.”

        Well it could happen . . .

    3. Jillm

      Once upon a time every smart person said that the earth was flat. Look at what happened to those who had another idea.

  5. Sylvia

    Was there sunlight in middle earth. Did they grow organically. Was it a happy place. Did they grow according to lunar influences. Wonderful post Dr Kendrick.

  6. Dr. Göran Sjöberg

    Great input again!

    This reminds me when I after my serious MI 1999 was immediately put on the full set of “heart medicines” and with that interest for sex disappeared. On follow up I mentioned that fact to my cardiologist at that time. He immediate response was that he was not to prescribe Viagra to me, even if I hadn’t brought this subject up, since it was “too dangerous for me”.

    Today this and all that medication is long time “history” for me but I wonder if ALL recommendations about serious health matters from the health care system are just the complete opposite to what is good for your health.

    1. David Bailey


      I wonder about this too – it is scary to wonder just how many other areas of medicine may be like this.

      I think what you encountered was lack of interest in sex rather than erectile dysfunction as such. I have always found that if I don’t feel well (even a cold is enough), my interest in sex vanishes at once. Is it possible that your heart medicines made you feel unwell?

    2. Mark Johnson

      This reminds me when I after my serious MI 1999 was immediately put on the full set of “heart medicines” and with that interest for sex disappeared. On follow up I mentioned that fact to my cardiologist at that time. He immediate response was that he was not to prescribe Viagra to me, even if I hadn’t brought this subject up, since it was “too dangerous for me”.

      Today this and all that medication is long time “history” for me but I wonder if ALL recommendations about serious health matters from the health care system are just the complete opposite to what is good for your health.

      From my research I’d say in 90+% of cases the simple answer is, “yes!”.

      1. Andy S

        Mark, a health care provider should be relabelled as “symptom manager” to better understand what to expect from the “health care” industry. Most drugs are designed to alleviate a symptom but create a few additional symptoms. Once you submit to their care you are on a merry-go- round of increasing tests and medications.

    3. Bill In Oz

      Your cardiologist was a prurient, arrogant bastard Goran ! Who is he to determine for you, what risks. you should take ?
      I think you are right in your comment that the ‘Standard ‘ recommended in this heart disease issue, is indeed the opposite to what is good for health.

      1. Dr. Göran Sjöberg


        “Your cardiologist was a prurient, arrogant bastard Goran !”

        Well I don’t know this about my first one since he was reasonable and I could talk with him at our regular meetings following my MI during full five years and he would listen to me even if he did not agree with my CABG refusal and my decline of all medication though sometimes we agreed on details.

        Though my second (and last?) cardiologist, which I met only once fit your characteristics all too well. This one immediately declared that he was not the least interested to hear what I had been up to during the fifteen years since my MI. All was nonsens in his mind.

  7. JDPatten

    Again, brilliant. Your presentation cannot be argued with.

    Except this small detail:

    “The clot is then drawn into the arterial wall…” seems at odds with your previous description which is something like: A clot forms where the endothelium is damaged or missing. Progenitor cells then provide new endothelial cells to cover that clot. “Drawn” sounds too much like an active verb – too much like what you argue against.

  8. Kathryn Bosse

    How does one know if the ‘endothelial cells’ of ones system are healthy or not? Like if your CBC / BLOOD report is perfect, are your endothelial cells in good shape. How would one monitor the health of their ‘endothelial cells’ via the diagnostic testing avenue of our societies.

    Second, If your endothelial cells are in good shape, do you really need blood thinning drugs.
    I would like to hear from the professionals participating in this BLOG, on these two questions, if that is permissible.

  9. Keith

    This is fantastic. I think you’re nearly there with the ‘endothelial damage/clotting’ hypothesis. Time for a new book to tie it all together?

    I think it’s telling when the medico-pharma-industrial complex calls anyone who questions or disagrees with the establishment “deniers.” It’s a pretty good indicator that the “deniers” are onto something. We’ve seen it happen far too many times in the past for it to be a coincidence, eg, leaded gasoline/petrol, smoking, fluoridated water, mercury amalgams, antidepressants, etc.

  10. Harry de Boer

    Dr. Malcolm, you’re almost there!
    Another great mind, Dr. Linus Pauling, already found out that endothelial disfunction is the cause of CVD. Only he (and not only he) went one step further by asking what caused this dysfunction, and they concluded that it was a modern-day version of scurvie. It can be treated with Vitamin C, and the ‘invasion’ of LDL can be prevented (or even undone?) with quite a high consumption of L-lysine which seems to bind to the ‘lysil groups sticking out of the endothelium, latching on to the Lipoprotein(a) in LDL otherwise’. (Also heavily paraphrasing.)
    But who knows, maybe I’m just another vit c nutter, only future will tell…

      1. Harry de Boer

        A very interesting question indeed. Or was it a counter argument? If the latter, then could you please elaborate a bit?

  11. Helissa Penwell

    “One which fully supports endothelial damage as the first step in plaque formation.”–Actually, wouldn’t that be the third step? The second is what triggers the damage, and the first is why the blood vessels have become vulnerable, rather than being healthy and resistant.

    1. Andy S

      Helissa, I agree with your line of thinking. My understanding is that the endothelium is vulnerable, not becomes vulnerable. The problem seems to start with high steady and postprandial glucose levels that the blood vessels were not designed to handle.

    2. roger

      A very long time ago before cholesterol and statins…SciAm had an article on heart attacks and presented data that showed a classic new infectious agent introduced into a non-immune population growth curve…

      Draw your own conclusion.

  12. abamji

    Another splendid piece, Malcolm. However two things: You quote “‘We are losing the battle for the hearts and minds of our patients to websites developed by people with little or no scientific expertise, who often peddle ‘natural’ or ‘drug-free’ remedies for elevated cholesterol levels,” adds Steven Nissen. ”

    In Nissen’s original piece a certain illiteracy is present, as “peddle” is written as “pedal”. Secondly I am surprised you have not risen to the bait regarding the websites “developed by people with little or no scientific expertise”. I have taken exception to that bit, and have left an online response with the Annals. So far it has not appeared but I will keep checking (comments are moderated, but mine may be too immoderate). However such mudslinging, akin to accusing statin “deniers” as being in the same league as Andrew Wakefield, are almost libellous.

    I ended my piece by suggesting that scepticism is to denial as agnosticism is to atheism… for myself, your endothelial damage hypothesis has not encountered any of the Black Swan facts that knock the cholesterol hypothesis for six, so I will stick (sic) with it!

    1. Stephen Rhodes

      Off topic, sorry but I have to take exception to the ‘same league as Andrew Wakefield’ comment.
      Having watched an interview where he explains the facts around his ‘crucifixion’ by the medical/pharmaceutical complex – aided and abetted by the venal British ‘meeja’ – I saw a doctor acting for his patients, trying to understand what was causing their developmental regression.
      Now that it has finally been accepted by the CDC that Thimerosal in vaccines can cause severe neurological damage in susceptible children – at a ratio of 4:1 boys to girls due to ethyl mercury’s synergies with testosterone – Dr Wakefield is now suing the BMJ in a Texas Court.

      1. Stephen T

        Stephen, I am now deeply sceptical of vaccinnes. Why do they not do comparisons of vaccinated and unvaccinated children? It would be so easy to do. I don’t think they want to find an answer that will damn them.

        I really can’t decide whether Andrew Wakefield is hero or villain. He was struck off, but I’m not sure of the details. I think the people who question vaccines might not get a better hearing if Mr Wakefield was less prominent in their movement.

      2. Sasha

        The book “Science for Sale” has a whole chapter devoted to Andrew Wakefield and how his findings were relevant. Even though the author, a scientist himself, has nothing to do with medicine and was an EPA whistleblower.

      3. Gary Ogden

        Stephen T: Read his book, “Callous Disregard.” Also read Dr. David L. Lewis’, “Science for Sale,” which also discusses what the British establishment did to this fine man. Also read the British High Court decision fully exonerating Professor John Walker-Smith, Dr. Wakefield’s co-defendant before the GMC. Dr. Wakefield is all hero. The villains are the pharmaceutical industry, BMJ, and elements of the British government and media. He was to be their example. Mess with our lucrative scam, and we will attempt to crush you. He, however, is uncrushable. The paper The Lancet retracted was good science, and never should have been retracted. It is now known (even mainstream medicine acknowledges this) that 75-80% of autistics suffer from moderate to severe bowel disease. This is what the Royal Free team discovered. This was pioneering work.

      4. Gary Ogden

        Stephen Rhodes: Thank you. Dr. Andrew Wakefield is one of the finest, both physician and human being, a man of real character. The Texas libel suit was thrown out on a technicality, the judge agreeing with the BMJ attorneys that the court lacked jurisdiction, even though the print version of BMJ is available for sale here. Professor John Walker-Smith, his co-defendant before the rogue GMC, and whose insurance carrier agreed to fund an appeal, was fully exonerated by the British High Court, Justice Mitting calling GMC incompetent to even understand the charges. Dr. Wakefield’s insurance carrier refused to fund an appeal. He is doing good work yet though, making films, speaking in public forums of the risks of injuries from vaccination in those vulnerable to them during the critical period of brain development, meeting with President-elect Trump. They chose the wrong man to attempt to destroy.

      5. Socratic Dog

        I also take exception to the slander. If I were to compare anyone here to Wakefield, it would be Malcolm, and I mean that in a very positive way.

  13. Barrycoll

    Dear Doc…..Is the restoration of endothelial function the rationale behind the suggestion that 5.4 supplemented grams of K results in similar CV health outcomes to Viagra?

    Is the mechanism similar??

  14. sundancer55

    So does this mean viagra is a good thing??

    Don’t beets contain a higher amount of nitric oxide than viagra? And wouldn’t it be healthier to use beet powder or juice or some form of beets daily than take a viagra daily??

    I’m confused, I guess.

    1. Bill In Oz

      Sundancer, beets are touted as a high source of potassium. But as I have said before here, beets cannot ‘source’ potassium if it is not already in the soil.
      Further while there are chemical fertilisers with potassium in them, potassium is extremely water soluble and is easily leached out of the soil by rain, if it is not bound up in organic molecules in the soil. We do not get good food from crap soil !
      This makes the whole matter of sourcing potassium in food somewhat problematic. And lack f potassium may underlie the whole heart disease epidemic of the last 40-50 years. See Dr Kendrick’s own post on the value of Potassium earlier in this series.

      1. Harry de Boer

        That’s why I neutralized my daily high-dose vitamin C intake with a mixture of Sodium bicarbonate, Potassium carbonate and Magnesium carbonate. One could even include Calcium carbonate if taking sufficient K [1,2].

        Question: Where (source) does your 5.4 g ‘K’ come from? And is it K1, K2-4 or K2-7?
        [1] Dr. Kate Rhéaume-Bleue: The Calcium Paradox
        [2] Dr. Thomas E. Levy: Death by Calcium

    2. Eric

      Beets contain nitrate, which can be converted to NO.

      Viagra contains no NO but appears to stimulate NO production

      1. Kathryn Bosse

        How about making your own beet juice. Drink some every day. That is my suggestion for (NO) production / enhancement . I also think keeping the endothelium healthy is a great start to a CVD problem. It is my first priority.

      2. Frederica Huxley

        We go one step further – we make fermented beet kvass! Easy to make, it is actually delicious. We add a handful of elderberries and blackberries to chopped beets, which adds to the efficacy of the kvass while losing the earthy taste of the beets.

      3. Gary Ogden

        Frederica Huxley: I’ve had a difficult time adding blackberries to ferments. They seem to turn to alcohol because of the yeast they contain. Perhaps a few wouldn’t be a problem. I actually like the flavor of the straight beet kvass, although I now add the potassium bicarbonate to it, which makes an interesting flavor. I must say that, in addition to the beet kvass, taking the potassium and extra salt before exercise has improved my exercise endurance, recovery, and feeling of well-being during exercise.

      4. Augustine

        Isn’t L- Arginine the same as Nitric Oxide? I’ve read it has a beneficial lowering effect on raised blood pressure along with grape seed oil. Any comments on this would be helpful. Thanks

      5. Dr. Malcolm Kendrick Post author

        l-arginine is a co-factor, with Nitric Oxide Synthase, in the production of NO. It is not the same thing, but if you do not have enough l-arginine, you cannot synthesize enough NO.

      6. Gary Ogden

        And the best food sources (for l-arginine) are nuts and seeds, seafood (especially tuna, salmon, and shrimp), and eggs.

  15. Brian Wadsworth

    Really interesting idea. Viagra as the successor to statins for the role of CVD superdrug. Now the questions Malcolm. Adverse effects? Suitable for women one assumes. Should otherwisw healthy people consider taking it or should it be a response to symptoms. You are a true agent provocateur of the best kind. Thank you

  16. Mark Johnson


    It’s difficult to understand how the likes of Prof Sir Rory Collins, Prof Michael Oliver etc can deny the massive effects of Viagra on CVD deaths and also deny therefore, the logical conclusions.

    Maybe they should try some Viagra themselves to get some more blood into their grey matter since their arguments are increasingly flaccid.

  17. Frederica Huxley

    Interesting, given that statins have been cited to cure a multitude of diseases and syndromes, I have never seen any reference to curing erectile dysfunction!

  18. Brian Griffin

    Hi Dr. K and thanks again for your ongoing contribution to the rational, thoughtful and unbiased discussion around this disease.

    As a person with the classic history of one serious MI (1 stent), chest pain/arterial blockages (for a total of 5 more stents), peripheral arterial disease in my legs, T2 diabetes (well controlled), and a level of ED this Swedish study interests me greatly. Unfortunately while it is stated that the effect seems dose dependent, this extract from the study doesn’t really shed any light on what that dose might be: ” where men with two to five, and more than five dispensed prescriptions had the strongest risk reduction”. What does a ‘dispensed prescription’ represent in Sweden? I use sildenafil and have done for some years but it certainly hasn’t prevented me having cardiac events from 2013 up until the most recent a few weeks ago. Of course there is nothing to say that I may have had more or worse had I not been using sildenafil. I would certainly be happy to take a regular dose for the therapeutic benefits if some dosage guidance could be forthcoming as I don’t have any side effects worth mentioning from using this drug and the benefits far outweigh those.

  19. Gary Ogden

    My vote for Steven Nissen for Time magazine propagandist of the year. He would fit well with the usual ilk who appear on the cover of that rag: Ancel Keys (twice!) and Richard Pan, for example.
    Seems like Viagra is way better than statins, and a lot more fun, too. Three cheers for NO. May we all produce lots of it from our Viagra-induced exercise.

    1. Bill In Oz

      Steven Nissen – A promoter of Statins so he must be an advocate of ‘Statinology’, Hence Statinologist” ?

      By the way I like the Tolkien reference. But surely it is
      “STATIN to rule them all
      And in the darkness bind them”

      1. Gary Ogden

        Stephen T: Thanks. Excellent article. I’ll forgive Dr. Fung for not having researched vaccine injury (not just celebrities, but tens of thousands of ordinary parents have reported the same thing: regression of a healthy infant or toddler after vaccination; the cause is chronic microglial activation, which short-curcuits brain development). Far more damaging than statins, but far more toxic for a physician to publicly discuss. On a positive note, last year’s election has reduced Americans’ already low trust in experts in general, so Dr. Nissen is basically pissin’ up a rope. Does he think people are that stupid that they don’t recognize the propaganda buzz words that he uses liberally in his advertisement?

  20. xtronics

    The PDE5 inhibitor paper is here if you want to get to the details.

    As a patient with serious CAD, I started taking Tadalafil (longer half life than Viagra) years ago to replace the 5g/d arginine regime I picked up from Dr. Davis.

    What is so strange is that the original study of PDE5 inhibitors was for heart disease – but the statins mantra was in bloom and they got distracted by a side effect.

    The above is not the only paper on PDE5 inhibitors and heart disease – I have a few more here

  21. drjohnc


  22. metaskepticism

    Hi Malcolm, thanks for another great post.

    There are a couple of points I would like to make; the first relates to Stephen Nissen’s comment:
    ‘We are losing the battle for the hearts and minds of our patients to websites developed by people with little or no scientific expertise, who often peddle ‘natural’ or ‘drug-free’ remedies for elevated cholesterol levels,”

    Now I don’t know about you, but I find my patients are often highly scientifically literate and highly motivated. Most of them have enough science and maths under their belt to start looking seriously at studies and analysing them. When their statistical knowledge is weak it is easy enough for them to ask questions and get answers on websites like this.

    One of the key ploys used by pharmaceutical companies is to create and groom “Key Opinion Leaders”. (I know this perfectly well because I was paid to attend a lovely dinner held by an ad agency in which they spent most of their time probing to discover what information sources — lovely food and wine and great sport to make up answers that were deliberately confusing :).

    However the market value of the created key opinion leader is destroyed if just anyone with an education can go and make their own analyses of data. I’m sure that the likes of Dr Nissen regard your cholesterol blog as being immensely impertinent! Imagine– a mere GP like you having the hubris to comment publicly on a specialist subject!

    All humour aside, the method that allows pharmaceutical companies to prosper is to create a situation where only a few favoured voices are accepted as experts. This ploy is offensive and destructive, and without it the cholesterol/statin fad would have imploded years ago.

    Point 2 can come as a second comment.

    1. Craig E

      Yes and the few favoured voices are allowed to get away with statements like ‘it just does’ when answering questions about, for example, how cholesterol causes heart disease or ‘there have been countless studies…’ without citing a single one. How do I get my ‘expert’ credentials?….oh wait…what’s that at the bottom of the cornflakes box?

  23. metaskepticism

    So point 2– much shorter. You may be aware that the amino acid arginine is very useful in increasing endogenous production of nitric oxide. Walnuts have plenty, but one can only eat walnuts so often before it gets boring. Have you looked at any studies in to arginine supplementation?

    1. KidPsych

      From what I can gather, L-Citrulline appears to be more effective in generating L-Arginine than Arginine itself. (Although I’m happy to hear of any contrary evidence – I still have a big bag of Arginine in my cupboard.)

  24. Charlie

    There is a natural PDE5 inhibitor icariin that seem to have multiple benefits and don’t have the side effects of statins.
    Pharmacology effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii
    Herba Epimedii is an important medicinal plant which has been used in various traditional Chinese formulations for thousands of years as well as in modern proprietary traditional Chinese medicine products. It has extensive clinical indications, especially for the treatment of sexual dysfunction and osteoporosis. There have been more than 260 chemical moieties identified in the genus Epimedium most of which belong to flavonoids. Icariin is the most abundant constituent in Herba Epimedii. Icariin is pharmacologically bioactive and demonstrates extensive therapeutic capacities such as osteoprotective effect, neuroprotective effect, cardiovascular protective effect, anti-cancer effect, anti-inflammation effect, immunoprotective effect and reproductive function. Particularly, the significant osteogenic effect of icariin made it a promising drug candidate in bone tissue engineering. The current review paper aims to summarize the literatures reporting the pharmacological effects of icariin. The pharmacokinetic properties of bioactive ingredients in Herba Epimedii have also been discussed.

  25. Andy S

    Appears that VIAGRA can increase NO caused by decreased NO production due to endothelial dysfunction. Hyperglycaemia causes chronic impairment of eNOS, mitochondrial and endothelial dysfunction (oedema + inflammation).

    1. sundancer55

      So . . . so . . . so . . . no one is going to respond to my question about using beet powder for the NO, rather than taking a drug like Viagra?? And are women supposed to ask for viagra, as well? Should it be only women who’ve already had a MI or just those who are worried they might?

      Sign me in as “still confused”.

      Moonlight and camp fires to all !

      1. Andy S

        sundancer55, searched “beets and blood pressure”. Yes beets and beet powder does lowers blood pressure probably by increasing NO. Personally when juicing vegetables I include a small beet. They are high in sugar so go easy. Could be many other benefits from consuming beets.

      2. barbrovsky

        I’ve been taking concentrated beetroot in capsule form (3500mg) for a couple of years now, twice daily. My last 24hr blood pressure test (the only way to be absolutely sure they’re not measuring the ‘white coat syndrome’ instead of my BP) gave a reading of Systole – 128, Diastole – 81. BTW, I’m 72, had a heart attack 51/2 yrs ago and had two stents fitted. I also take Ramipril 5mg (just to keep my GP quiet).

      3. Gary Ogden

        Andy S: I may be wrong, but I think fermenting the beets (for juice) converts the bulk of the glucose to lactic acid or some such. It certainly doesn’t taste sweet at all.

      4. Andy S

        Gary Ogden, I invested a bit of cash on a decent auger type of juicer that does a good job on fresh carrots, beets, parsley, kale, nettles, swiss chard etc.

      5. Mr Chris

        For blood pressure I found real beetroot as opposed to beet tablets more effective.
        However real beet has a somewhat earthy taste.
        So when I get back from hols, sitting on my boat reading about the ancient history of Turkey I will try to devise an experiment.

      6. Gary Ogden

        sundancer55: Yes to beets! I ferment them, and have 4 oz. (120mL), with potassium bicarbonate stirred in, twice a day. As I understand it, it is the nitrates in the beets which provide the ammunition the body needs to produce NO. I don’t know anything about beet powder, but I imagine it should work, too. The beet greens are about three times richer in K as the root, but both are good sources. I cook the greens for a bit in a little water to reduce the oxalates, and eat them a couple of times a week. K very important; NaCl too, and Mg. Most folks don’t get enough of them.

      7. Bill In Oz

        Sundancer, Ummmm Beet powder ? I do not know. But unless it is grown is soil with good levels of potassium, maybe not so useful. Iherb has potassium in reasonable amount per tablet and they accepted my order from Australia. Maybe not if you are in the US.

        Also new reading leads me to think that for men & women part of the answer is Chondroitin sulfate..Or at least a diet rich in sulfates.
        As Dr Kendrick says CVD is a result of stress from the physical pressure of continual blood flow in the coronary arteries. Sulfate is used by the body in the arteries to reduce friction of blood flow and thus reduce stress..And that reduces injury to the endothelium layer of the arteries.
        And bingo, that reduces CVD

        No sulfate in the diet = lots of CVD
        Lots of Chondroitin sulfate alleviates CVD
        Pioneered by Lester Morrison in the 1960’s-70’s. But he could not explain why it worked. This article explains it :


      8. Gary Ogden

        Bill In Oz: Stefanie Seneff at MIT has some interesting writing on her web page about the importance of sulfate in the diet (I attended her lecture about this.).

      9. Richard Moore

        Sipping my beet juice; organic,of course, mixed with a bit of unadulterated apple juice to soften the tartness, I often ponder what damage all that sugar is doing.

      10. Bill In Oz

        @Gary Ogden I have seen the article by Stefanie Sennef of MIT on Chondoitrin sulfate. Yes it’s interesting research.

        Lester Morrison in his 1960-70’s research could not explain scientifically why CS helped people who had had heart attacks. He just knew from his research and trials that it did. And was ignored.

        Sennef’s work explains the process: reducing friction of blood pumped in the arteries against the endothelium wall. Sulfate reduces the turbulence. Thus it reduces the damage. Less damage, less clotting, less plaques. Dead simple really.

        The hydraulic pressure that the heart generates as it pumps blood through the arteries, generates turbulence and wear & tear of the arterial endothellium layer. Lipoprotein Lp(a) particles ( dense & small & fast moving ) are the bullets doing the damage. Then the body responds with a blood clot to heal the constant wear & tear. And plaque forms over the clot like a cab does on the skin.

        An illustration : try holding your hand against the water coming out of a high pressure hose for a long period of time. The skin gets damaged an afterwards a scab will form ( a plaque )

        And this explains also why veins with no plaques grafted into coronary arteries quickly develop plaques as well. Stress, Wear & Tear.

        By the way have been taking CS as per Morrison’s 1973 research protocol. I started in mid June. Morrison had good results after 90 days at 10 grams a day & then 1 gram a day subsequently.

      11. Gary Ogden

        Bill in Oz: Thanks. In my long-distance running days I took CS, as it was recommended for osteoarthritis pain (mainstream medicine took every opportunity to belittle this recommendation). I did not know about the cardiovascular benefits. Very interesting. Since hearing Dr. Seneff’s lecture in 2011, I’ve increased my intake of sulfur-rich foods, such as cruciferous vegetables, eggs, onion and garlic, but it sounds like a supplement is worth considering.

      12. Bill In Oz

        Gary before my retirement in 2015 I was a commercial organic garlic grower with kale ( which I also love eating ) as a sideline. I also love red onions and ate plenty of them. So my diet was not deficient in sulfur…

        However I suspect that as we age the body’s ability to benefit from such dietary sulfur declines…So additional sulfur via supplements becomes needed.

        By the way aging has now been shown to be a ‘programmed’ process. There are body clocks in the body which are set to disregulate things as we grow older. I admire and agree with the work of Josh Mitteldorf in the USA. He has a really great web site on how to avoid aging…

      13. Martin Back

        If you want to see a molecule that has the potential to rip your endothelium to ribbons, find an image of the tetraethyl lead molecule. It looks like a three-dimensional swastika or ninja throwing star.

        I don’t know if it actually got absorbed unchanged into the bloodstream from petrol vapour, but if it did, with that heavy lead molecule in the centre, it is easy to imagine it being thrown against the endothelium by turbulence and scything chunks out of it.

  26. Brian Wadsworth

    If the idea of asking for Viagra is uncomfortable then consider asking for Revatio (Sildenafil) –

    “REVATIO is a prescription medicine used in adults to help treat pulmonary arterial hypertension (PAH). In PAH, the pulmonary arteries become narrow. This means there is less room for the blood to flow from the heart to the lungs. Your heart has to work hard to pump blood into your lungs.”


    1. Gary Ogden

      bfhu: First, reread all 33 posts in this series. What I can recall: Collagen is a major constituent of the endothelium, and both the amino acid glycine (rich in the skin, bones and connective tissue of the animals we eat) and vitamin C are critical for its formation. Thus, drink bone broth and take vitamin C. Also, vitamin E plays a role in endothelial health, particularly the d-tocotreinol form (best sources red palm oil and annatto seeds). NO is crucial, so get out in the sun, and do activities which raise your pulse at least 10-15 bpm on a daily basis. Also of great importance: Worry not, not the little things, not the big things (easy for us to do who are well-fed and live in developed countries).

      1. sundancer55

        Hi Gary, due to the nature of this blog’s comment section, I am going to post some information under YOUR comment because you mentioned collagen. 😉

        There was someone here (but I cannot find the comment even after scrolling through ALL of them at least 4 times) with the last name Moore who had asked a question about using juice to mix with collagen because he was worried about the sugar in the juice. Well, I mix my beet powder, my bovine collagen and some organic juice in a small cup (maybe about 3 oz) every day and have been doing it this way for about two years now. I was surprised to find the following information from Dr. Tim O’Shea but it helped settle my mind, too, about the juice/sugar aspect. Hope it does the same for Mr. Moore.

        ** Also, even though Dr. O’Shea refers to the type of collagen he sells – hydrolyzed collagen – that is not the kind I use, but I think the same aspects regarding sugar would apply no matter what type of collagen you are using. I buy mine online (there are several places to buy it) and it’s called Bernard Jensen Bovine Collagen. It’s a granular powder and I use 2 tsp along with 1/2 tsp beet root powder (from Mountain Rose Herbs) daily.

        Here’s the copy and paste version of the article to which I referred. Sorry it is kinda long and hope it copies here!


        During the past decade, hydrolyzed collagen has become very much in demand, going out all over the world. For best absorption, the label recommends that the collagen powder be blended in juice. Thousands of people seem to have achieved best results following this advice.

        Occasionally someone will express concern about taking in too much sugar when using juice for the blend. “I can’t take the sugar” is what they always say.

        Here are a few reasons why such concerns are groundless:

        1. Any fruit or vegetable juice can be used, including celery juice, cucumber juice, cabbage, kale, or any other juice.

        2. Orange juice is the most popular, being the most common breakfast beverage. Whatever juice you choose, we’re talking about 100% pure of course, no concentrates, nothing added, organic if possible.

        Now fructose is the natural fruit sugar in juices. If pure, the juice will contain within it all the vitamins and enzymes necessary for its complete breakdown into its simplest carbohydrate components. That’s called digestion.

        This metabolic process will not cause undue stress, abnormal insulin spiking, overtaxing the pancreas or any other adverse effect. No matter what you might read on google-pedia.

        Blood glucose will always be temporarily elevated following a meal that includes carbohydrates. That is a necessary sign of the digestive process. But it soon returns to normal levels between meals. Pure natural juices are not a cause of diabetes in today’s world. Just visit any supermarket and look down the double aisle of Coke, Pepsi, Dr Pepper, beer, etc. and see the real cause.

        How much of that is in your kitchen?

        You can actually mix the collagen powder in anything you want , and daily intake will eventually have a beneficial effect. But we have noticed over and over that pure organic juice seems to work best, for 2 likely reasons:

        1. It is suspended in a most easily absorbable medium

        2. whole food Vitamin C is an important factor in initiating the conversion of hydrolyzed collagen supplement into the body’s own new collagen.

        So, yes you can dissolve the Hydrolyzed Collagen in water or applesauce or milk, or sprinkle it over oatmeal – or mix it into any wholesome food – all of that works. Except coffee, of course – which is a non food – no nutrient value, and will dilute the value of this excellent supplement. (Yes, yes, I read that too – it’s nonsense. ) But for optimum results, most people just use the best organic fruit or vegetable juice they can find. That’s what most of those success stories in the “feedback” section did.

        So just forget about any imaginary issues about too much sugar, etc. Fruit juice is not the reason why almost 30% of the US population is diabetic!

        It would be intriguing to be able to look into the refrigerators and kitchen cupboards of some of these callers who are so worried about the ‘sugar’ in organic orange juice. Of course we’d find absolutely no Coke, soft drinks, cookies, donuts, liquor, beer, wine, cakes, pies, candy, chocolate, etc, just lying around…

        ​***** Here is the link to the section on collagen at his web site:

      2. Gary Ogden

        sundancer: The Bernard Jensen stuff is of high quality. I used to buy it myself. What I do is make bone broth, since I have easy access to good quality bones (feet are the best). I drink a cup first thing in the morning with butter and salt. I think the butterfat aids in absorption, and the salt in flavor. It is better taken in the evening for ease of sleeping, but I sleep like a rock, and I like it first thing in the morning. It is rich in gelatin-if I refrigerate it, it solidifies like Jello.

  27. Robert Bramel

    Once again you appear spot on. I’m 71, a familial hypercholesterolemic with LDL alone over 500 mg/dl, and yet with completely clear arteries by Electron Beam Computed Tomography (EBCT). Conventionally oriented researchers are universally amazed about my situation, enough that one Harvard researcher has done a complete genomic scan of my DNA, in the hopes of finding out the special genetics that “protect me from the obvious hazard of my extreme levels”. Your theory says that for whatever reason I have robust endothelium, and lipid levels make almost no difference. Which is the simpler, more plausible theory? Hmmmm.

    1. Dee

      Robert – It is very encouraging to hear that from someone with familial hypercholesterolemia! May I ask if there is anything specific in regard to lifestyle that you believe contributed to your clear arteries?

  28. Mark

    Dr Kendrick

    I think you’ve made some very important mistakes in interpreting the Viagra study data. Firstly you reported that “just over forty thousand had medication dispensed for erectile dysfunction (ED) (40,077), three thousand did not (3,068)”. If fact it was the other way round – 40,077 did NOT have ED treatment, 3068 did (see Table 1).

    Secondly, the data you reported appear to relate to a subgroup (>5 scripts) of a subgroup (PDE5 inhibitors vs alprostadil). I think you thought the analysis related to versus no treatment. Since only 254 men took alprostadil in the whole study the numbers of events were tiny. No causal inference here I’m afraid, just some interesting data worthy of further study. This highlights the importance of seeking out the actual number of events (or trying to), rather than just looking at the hazard or risk ratios. 23 died in the alprostadil group, and that’s before you split it into the prescription level groupings.

    This also highlights the value of reading what the authors think about their own results. The study authors stated:
    “Moreover, we found that there was a dose-dependent association between treatment with PDE5-inhibitors and risk for death, where men with two to five, and more than five dispensed prescriptions had the strongest risk reduction when compared with men treated with alprostadil. However, this finding has to be interpreted cautiously since the CIs were wide due to few cases. Although our results indicate that the reduced risk of mortality and hospitalisation for heart failure may be related to cardioprotective effects of PDE5-inhibitors themselves, our findings should be regarded as no more than hypothesis-generating.”

    1. Dr. Malcolm Kendrick Post author

      Mark, sorry for the delay in replying to your comment. I have been on holiday for a week and someone else was approving comments, but did not think they could respond to yours. You are right, I got the numbers the wrong way round. Forty thousand did not have ED medications and three thousand did. I have now edited the post.

      However, your other point I will disagree with. There have now been many different studies demonstrating benefits from PDE5 inhibitors, and this study was not merely hypothesis generating. The hypothesis had previously been generated. Namely, increased NO synthesis is beneficial for cardiovascular health. This, I do not believe to be a hypothesis, it has been supported by many different studies. Those drugs that reduce NO synthesis e.g. Avastin, omeprazole greatly increase CV death. Those drugs that increased NO synthesis e.g. ACE-inhibitors, statins, PDE5 inhibitors reduce CV death. There is a clear and well identified mechanism of action, there are no contradictory studies. Unfortunately there will never be a randomised placebo controlled double blind study done to confirm, or refute, this hypothesis as there is no money to be made. [At least not on existing medication]. Therein lies the fatal weakness of the current medical research paradigm. The ‘mainstream’ refuses to accept evidence that does not come from ‘gold standard’ clinical trials. Virtually the only organisations willing and/or capable of running such trials are pharmaceutical companies. So, we are trapped in world of research evidence that is run, controlled, funded by companies that have a vest financial interest in the outcome. Personally, when I see a HR > 5 I accept this as most likely causal. HRs of 1.20 (and suchlike) do little to excite me, even if the CIs are tight. These may be statistically significant. However, they are clinically irrelevant.

      1. Mark

        Thanks for replying, and for correcting the numbers. The point about the study results being hypothesis generating isn’t mine but the authors of the paper. Besides, I think we’re talking about different (although related) things – these authors don’t mention nitric oxide at all.

        Don’t be too despondent about the prospect of a future trial. Many trials are publicly funded e.g. by the MRC or NIHR (in the UK). For example, I posted a comment a few months ago about the MRC’s CRASH trial which has resulted in corticosteroids now NOT being routinely use to treat head injuries (bad news for some of the pharmas). There have been further CRASH trials.

        As regards evidence, please always be wary of impressive results which are based on small numbers of events – the play of chance is very real. This is also true for RCTs – many are too small and some are stopped too early where an apparently important result is seen (only for later studies to show this was in fact likely to be a chance effect).

        The truth is though that these days it’s very rare to find a treatment that will give you a result which ‘excites’. Small improvements (such as the HR 1.2 with tight CIs you mention) have been the mainstay of improved outcomes in common diseases such as cancer and CVD over the past 30 years. These are highly clinically relevant results when millions of people suffer from them (a 2% improvement in mortality means a heck of a lot of lives saved in absolute terms).

  29. gollum

    If you listen to Kuklinski, most problems are nitrostress and NO-promotors are very, very bad.

    Others claim that the “enzymes decouple” and go haywire if there is not enough arginine.

    Personally, I do calm my soul about my 2*5g arginine habit with the assurance that it is a basic amino acid, a substrate only. I wouldn’t be so calm about NO-forcing drugs. Poppers do have a reputation for being unhealthy.

  30. Mike Smith

    Another interesting read Malcolm, I am curious though, what was the frequency of the Viagra/Slidenfil and the dosage. Currently I believe the typical prescribed NHS dosage is 4 x 50mg tablets every 2 months for ED?

  31. Errett

    I was thinking about Mike Cawdery—–happen to read this—-

    “Statistics, because they are numbers, appear to us to be cold, hard facts. It seems that they represent facts given to us by nature and it’s just a matter of finding them. But it’s important to remember that “people” gather statistics. People choose what to count, how to go about counting, which of the resulting numbers they will share with us, and which words they will use to describe and interpret those numbers. Statistics are not facts. They are interpretations. And your interpretation may be just as good as, or better than, that of the person reporting them to you.”

    From a “Field Guide to Lies”–by Daniel Levitin

  32. Doug

    Hello Dr. Kendrick,

    I’ve been reading your blog for a number of years now and I’ve watched you bang your head against this wall all that time. You’ve been looking for the door thru the ‘damage -> repair, damage -> repair, damage -> repair = heart attack’ wall for as long as I’ve been reading. Have you thought that maybe there isn’t a door?

    The heart is a number of things:
    A hydraulic pump,
    Powered by a muscle,
    Controlled by a hormonal pathway,
    Operated by electricity.

    You’ve focused in on this one thing, one may even call it a hidden bias in your quest.

    But we know only one thing for certain; there is a heart attack. That’s it.

    Is it caused by a failure in the hydraulic system? The muscular system? The hormonal system? The electrical system?

    The one thing that bothers me is that a heart attack episode has a duration, it could be minutes but it could also be hours. This speaks to a process, the process of the heart attack. All human processes have many, many players, not the least of which is the repair mechanisms, cause and effect. Which is the cause and which is the effect?

    And I know someone will say, ‘but what about a stroke?’ what about it? Where is it written that the two are connected? My father had three strokes while on chemo meds, a stroke may be part of the damage -> repair pathway but does that automatically mean it’s part of the heart attack event?


  33. Doug

    As an aside,

    I have two friends who had heart attacks at 35.

    Friend one didn’t go the hospital for hours and when he finally arrived they gave him a stint to open the blockage.

    Friend two was at the hospital within minutes of the onset, pumped full of NO, to the point where he (now she, so I’ll use the proper pronoun) says that the NO headache was almost worse than the attack, even though during the attack she was completely unable to move because of the pain, which she describes as something you wouldn’t wish on your enemies. Subsequent investigation showed no blockage and no damage therefor no stint.

    How can both these event be explained by the ‘damage -> repair’ hypothesis? Occam’s razor favours simple theories. The simple theory would be that the repair happens after the event. Friend one had time for repair to begin. Friend two’s quick intervention prevented damage therefor no repair was needed?

    I don’t know much, but I do love a good mystery.


    1. Dr. Göran Sjöberg


      “I have two friends who had heart attacks at 35.”

      Talking about the probability of getting a MI at such a young age I thought it was almost quite impossible to know two persons of this kind.

      The only thing I can think of is that they both had familiar hypercholesterolemia.

      1. Doug

        Yes, both high stress and poor diet but ……..

        One fits into the normal mold for MI but the other doesn’t. He (She) had a ‘widow maker’ heart attack, she should have been dead within minutes except for the close proximity to a small town hospital and immediate medical intervention. She’s the one that had no clot, no damage, no apparent reason for the attack.

        It’s these outliers that bother me:
        The extreme athlete that drops dead at 55.
        The 18 year old who consumes an energy drink and drops dead during a sports game.
        The 35 year old fat, stressed out, smoker/drinker, non-exercise victim with no apparent blockages.

        What do they have in common with each other?

        If you include my first friend who had a ‘normal’ MI then we’re looking at 4 different mechanisms? No, that doesn’t make sense. I struggle to believe the damage -> repair, damage -> repair, damage -> repair = Heart attack hypothesis.

        I’m not saying we shouldn’t strive to prevent damage, I’m seeing remarkable markers of improvement following Pauling and Dr. K’s ideas, along with many others mentioned here, it’s just that we’re no closer to the actual trigger mechanism of the MI. I’m just openly questioning the damage -> repair garden path we’re all merrily skipping down together with our glasses of Vit. C and bottles of Scotch, with all due respect of course.


    2. Gaetan

      There could be many, many reasons. Stressful Jobs, marriages, bad relationships with family, kids & friends. Them being under Chronic stress for many years. Cocaine, yes i wrote cocaine as in sniffing it or freebase. Complete lack of exercises or sedentary lifestyles. Bad diets. Lack of sleep. Etc.

  34. Doug

    Why do ultra marathoners drop dead of heart attacks? Is it because they don’t allow the heart as muscle to heal itself? Do they tax the control system to extreme? Is it a lack of hydration that tips the hormonal balance? Sooooooo many questions

  35. Mark Johnson

    Once again you appear spot on. I’m 71, a familial hypercholesterolemic with LDL alone over 500 mg/dl, and yet with completely clear arteries by Electron Beam Computed Tomography (EBCT). Conventionally oriented researchers are universally amazed about my situation, enough that one Harvard researcher has done a complete genomic scan of my DNA, in the hopes of finding out the special genetics that “protect me from the obvious hazard of my extreme levels”. Your theory says that for whatever reason I have robust endothelium, and lipid levels make almost no difference. Which is the simpler, more plausible theory? Hmmmm.

    Robert, maybe you should tell your Harvard researcher to contact these Harvard researchers which The BBC yesterday (1 August 2017) picked up on and published the usual bollocks story about “bad cholesterol and statins”:
    Should you be taking statins? Research from Harvard University suggests “almost all” men over 60 and women over 75 should be doing so in order to help prevent heart attack and stroke.


    To justify that practically all the elderly should be taking statins was the following statement written I’m sure, without any intention of irony: This is because age is one of the main factors when it comes to estimating risk of disease. No shit Sherlock. And they wonder why poly-pharmacy is rife among the elderly – give the elderly enough meds and they’ll live forever!

    1. Antony Sanderson

      Is there no one on the BBC news editorial team that does not recall studies that have shown that statins may have a small beneficial effect on preventing CVD event, but that there is no beneficial effect on overall mortality. So you might not die of of a heart attack, but you are more likely to die of cancer.

      Whenever there is an anti-statins report on the Beeb . . they always seem to have a sudden attack of impartiality and wheel out pro-statin grandees – usually Rory Collins – to provide a “bit of balance” . . . don’t you know.

      There ought to be a rule . . . whenever statins studies become news items . . . whether for or against . . . they subject should be labelled as “controversial”. Such a label might poke a few more people to look into the subject and discover what a con the statin/lipid-heart hypothesis is.

      1. David Bailey

        The BBC lost its sense of balance on a whole range of topics. For example, when do you hear from any of the many experts that doubt the whole ‘Climate Change’ agenda?

  36. Craig E

    Perhaps then warfarin can be replaced by Viagra? Or better yet…daily sun exposure. Who would have thought the union of N and O would provide so much!

  37. Martin Thomason

    Having suffered an MI and stent implant 2 years ago, at the age of 45, I have read everything I can get my hands on since then to reduce the risk of a repeat event in future. The endothelial damage hypothesis being the trigger for atherosclerotic plaque formation seems the most logical process; like others I want (need !) to know what causes the damage in the first place, so that by working backwards I can prevent the plaque cascade before it begins.
    As such, Andy S has hit on a highly likely culprit – high blood sugar levels. On Dr K’s previous post where Professor Salim Yusuf stated that the biggest risk factor for CVD was excess carbohydrates (>50% calorie intake derived from carbs) then this perhaps explains why it is the ‘bun and not the burger that will kill you’ – the excess blood glucose and associated high insulin levels being the suppressor of Nitric Oxide production and hence the causation of that critical first step of damage to the endothelial cells.

    The roller coaster ride of blood sugar following high carbohydrate meals is well documented, with the rise in blood glucose triggering the surge in insulin that causes the blood glucose levels to fall and subsequently trigger the hunger signals to eat and thus restore the blood sugar level. If carbohydrate is eaten to meet this hunger pang, then the process is repeated over and over again. The endothelium would never gain the respite needed to deal with the ongoing damage. A high fat, low carb approach prevents the raised blood sugar and does not trigger the insulin response – so no hunger pangs and no frequent intake of carbs throughout the day: resulting in a cardio-protective outcome.

    Does anyone have more information that perhaps confirms this as a possible trigger / causation in CVD ?

    Keep up the excellent discussion – we’ll get this nailed together !

    1. Stephen T

      Martin, did you see Dr David Diamond’s talk on YouTube that I attached to Dr Kendrick’s previous post?

      1. Martin Thomason

        Found it Stephen, many thanks; a good summary of most of what we now know, although no focus on endothelial damage being the initiator of the process leading to full blown CVD. I must admit to being a little confused at the end with the discussion around platelets and clotting as Dr Diamond seemed to be suggesting that circulating clots (platelets activated by blood sugar, physical inactivity, etc) were the cause of heart disease and that aspirin had no effect unless you were actually experiencing an MI.

      2. Antony Sanderson

        Hi Martin . . . My understanding from what David Diamond was talking about at the end of the talk was MIs (Heart attacks) – not CVD as such. So I took him to mean that if you had a vascular inflammatory situation, caused by damage to the epithelium, the response might be mild for many (possibly a small clot – soon cleared up) . . . . . but, for people with overzealous platelets and buckets of fibrinogen to hand, a response to even a small amount of damage might be to escalate things to a super-dooper thrombosis, leading to an MI.

        So the CVD – the damaging of the heart vasculature, involving damage to the epithelium – sits as a backdrop, ready for the coup-de-grace of a massive clot leading to an MI. The more damaged the heart, the greater likelihood of a clotting event . . . The more prone to clotting, and the greater the level of clotting response, the more likely the event will develop to be life threatening.

        What it says to me is that if you have a super-charged clotting system you need to make sure your vascular epithelial health is top notch.

      3. Mr Chris

        Antony Sanderson
        What it says to me is that if you have a super-charged clotting system you need to make sure your vascular epithelial health is top notch.
        Agree, do you have any great easy ideas?

      4. Martin Thomason

        Thanks for clearing that up Antony – that makes sense – I’d misunderstood the context. Regards my MI, when I asked the cardiologist who fitted the stent what had caused the MI, he just replied ‘a blood clot’ but no further explanation was provided! Not being as well read on the subject as I am now, I remained puzzled as to where the clot had come from.

        Your description of events seems to offer two possibilities – a circulating small clot that was the focus for platelet aggregation due to an imbalance in clotting factors, or a ruptured plaque that spilled its contents into the lumen, triggering the super clot that caused the MI. I seem to think it was the latter, because having removed the clot, the stent was needed to open out the artery.

        It would have been helpful if the cardiologist could’ve taken the time to better explain what he understood the cause to be. Incredibly, the first meal they offered me the following day was chips !!! I declined.


      5. Antony Sanderson

        Mr Chris
        Re: Keeping the epithelium healthy
        The prime thing I do is to eat low carb – keeping the glucose in the blood to reasonable levels.

        (After 3 years on statins I sort of drifted into being diabetic – Each year the HaA1c gently rose – ironically, at the same time I was losing weight, cutting the alcohol, increasing exercise – At the point of diagnosis I had to find out why I was in danger of losing limbs. . . . Discovered the damaging nature of sustained glucose levels to the endothelium in the peripheral vasculature. When I discovered this it seemed to me that glucose damage was probably what had instigated the small to medium blockage in one of my coronary arteries – I also thought that the high glucose would explain why diabetics are more prone to heart events than the average )

        Sustained high levels and even higher peak levels of glucose seem to be damaging to the endothelium’s glycocalyx protective layer . . . It seems likely that this is one of the things that can start things of.

        I go with a number of others on this blog who advocate beetroot as being heart healthy – as I understand it the beet provides nitrates which provide a source of NO. The NO seems to contribute to a healthy endothelium. Always have some pickled beetroot on the go.

        I am told that rocket (arugula) provides the body with the resources to make NO. (Better source than beetroot?) So I regularly have a lunch of a soft boiled duck egg or tin of sardines on a bed of rocket/water cress/cooked cauli/broccoli with homemade mayo (olive oil) . . . if it doesn’t look green enough I put a handful of spinach in as well.

      1. Martin Thomason

        Thanks for the suggestion Roger – I shall add to my growing library of books !


    2. Andy S

      Martin, There is quite a lot of information on GLYCOCALYX and its importance in cvd. Looks like endothelial dysfunction and inflammation starts with damage to the glycocalyx that lines all blood vessels (the teflon coating analogy). Steady state and post prandial glucose plays a big part, and can be controlled by LCHF diet. Applies to everyone not just diabetics. There are many other factors as well: mitochondrial health, Mg, C, Se, linoleic acid, TG, oxLDL, metabolic overload, etc. etc..

      QJM. 2008 Jul;101(7):513-8. doi: 10.1093/qjmed/hcn024. Epub 2008 Mar 4.
      Hypothesis: arterial glycocalyx dysfunction is the first step in the atherothrombotic process.
      Noble MI1, Drake-Holland AJ, Vink H.

      We present evidence that the 0.5 microm thick gel layer, lining the inner wall of healthy blood vessels, the glycocalyx, is the first line of defence against atherothrombotic disease. All blood vessel linings are coated with this gel, a highly negatively charged structure, rich in anionic sites mostly represented by the sialic acid moieties of glycoproteins and the sulphate and carboxyl groups of heparan-sulphate proteoglycans. Blood flow in arteries is associated with a shear stress at the glycocalyx, which signals the underlying endothelial cells to release nitric oxide (NO), an anti-atherogenic factor. Sites of low shear stress in the arterial tree are more susceptible to atheroma due to lack of NO generation through this mechanism, whereas exercise, by increasing blood flow and shear stress, is protective. We postulate that risk factors for atherothrombosis act by impairing glycocalyx function. THAT LUMINAL HYPERGLYCAEMIA CAUSES GLYCOCALYX DYSFUNCTION HAS ALREADY BEEN SHOWN; we postulate this to be THE FIRST STEP IN THE ATHEROTHROMBOTIC PROCESS in patients with diabetes mellitus and metabolic syndrome (insulin resistance). There is also evidence of glycocalyx defects from exposure to oxidized low-density lipoprotein. We postulate that other risk factors will have a similar action on the glycocalyx as the initiating factor in the disease process, e.g. smoking, hyperlipidaemias and hyperhomocystenaemia. These predictions can now be tested in a large animal model of shear-stress-mediated arterial dilatation.

      1. Martin Thomason

        Andy – thanks ever so much, this is a revelation to me as I was unaware of the existence of the glycocalyx layer and the proteinaceous ‘hairs’ within the glycocalyx gel layer that allow the endothelial cells to ‘sense’ the changes in shear stress (caused by the blood flow within the lumen) and so to trigger release of NO. Explains perfectly why exercise is so beneficial (one of my cardiologists told me that exercise is the single factor with the greatest impact on heart health – being more effective than statins, beta blockers, and blood pressure medication combined. Exercise increases the flow of blood increasing the shear stress and hence triggering the release of NO from the endothelial cells, the NO assisting the anti-adhesive property of the glycocalyx and being anti-inflammatory; also causing the smooth muscle cells lining the artery to relax, increasing the diameter of the vessel and allowing freer blood flow.

        Prior to my MI, I had an horrendously sedentary lifestyle, compounded by a large carbohydrate load caused by rice, pasta and potatoes that I believed were healthy and low fat. I can now see where things started to work against me. Although never diabetic (I have regular medical screening for my job), I believe the high carb load and lack of exercise were damaging my glycocalyx layer, exposing the endothelium to the blood flow and causing my artherosclerosis, eventually a rupture led to the clotting that resulted in my MI.

        Thank you again, I’m new to the forum, but the information sharing is incredible.

    3. gollum

      Sorry, I just took that as a given so I don’t have sources.

      Another possible mechanism is that high-carb eaters tend to have sky-high TRIGlyceride levels, (probably especially those who are overweight and having them leak out of the adipocytes).

      I forgot the exact mechanism how those are damaging you, maybe they do indeed “stick to your arteries”. Or maybe the free fatty acids give wrong metabolism signals (palmitic acid and so on) and/or lipid peroxidation. (Guess what doctor cares about? Not TRIG but LDL, and LDL often via the dreaded Friedewald)

      I understand that I am being a wuss here. For my purposes (understanding/practical diet) this looks dangerous enough.

      Peter D from hyperlipid/highfatnutrition had a speculation about how the heart could drown in a sea of glucose, causing CVD event. It had to do with metabolic signalling and evolutionary preferring FFA. The observation that many heart attacks occur at dawn 04:12 am (fasted state) fit that, too, IIRC. Vague description being not very helpful but I cannot find it right now. I recommend to read all of his blog, anyway.

      1. chris c

        Agree on Peter’s blog, but some of you may need a brain transplant in order to understand it. I know I did . . .

      2. chris c

        I bought it from a dietician. It had hardly been used.

        It’s obviously become a common operation, if little discussed, there are a LOT of post-operative brain donors around, Parliament and Upper Management are full of them.

        Going back to trigs, a LOT of people are no longer given this result from a lipid panel, only Total Cholesterol, HDL and a Ratio. This makes no sense as LDL is usually (not always) calculated via Friedwald Equation and to do this trigs need to be measured. Looks like the result from some El Cheapo lab analyser.

        This makes me suspect it may actually be a useful metric which is why it is being concealed from patients. IMO it is a surrogate for excess carb consumption while HDL is a measure of fat intake in the absence of the carbs. Trigs/HDL is a good estimation of insulin resistance, also particle size and density of LDL and actual CVD risk. Maybe the assumption is that it is going to be high from the recommended HCLF diet, in fact I’ve heard of patients being told to “stop doing LCHF, Atkins, Paleo etc. and we can tell if you are complying because your trigs will increase”, and even read some Vegans who claim that high trigs are good. It’s those Holy Health Grains and low fat fructose.

      3. Gary Ogden

        chris c: On this side of the pond, upper management is riddled with them, too, but in the case of Congress, one of the qualifications to run for that august body is to lack one entirely; they are required to donate them to the dietitians.

  38. Sylvia

    We can get very stressed out at trying to keep healthy. Easier said than done, to be relaxed and serene after driving in busy traffic to spend the day in another stressful situation, then do it all again in the drive home. Make a healthy meal for the family, spend some quality time with them! But, if unemployed, more stressful. Welcome to the modern world. The consequences of this mad lifestyle must inevitably lead to dis ease. Of course the society we have apparently chosen is so unhelpful to our wellbeing, the remedy is a hard pill to swallow. Less greed.
    Not so simple I guess. So enjoy all the comments on your blog Dr Kendrick. Best wishes to all.

    1. Sylvia

      My former comments straying again, sorry. Reading about Viagra, one report says it should not be taken if you are also on nitrate drugs for chest pain, can lower BP too much. Perhaps you have already said as much, or others and I have missed it. Lots on GTN’s and such.

    1. Errett

      Rotten egg gas could help protect diabetics from heart complications.

      A gas that was formerly known for its noxious qualities could help people with diabetes recover from heart and blood vessel complications, concludes research led by the University of Exeter Medical School.

      The research could help pave the way to new treatments for some of the most common complications association with diabetes. Heart problems are a common cause of disability and death in people with diabetes, and are expected to rise still further with increasing rates of obesity. Currently, 79% of the £14 billion spent on treating diabetes in the NHS is spent on treating complications.

      Laboratory research published in Pharmacological Research and funded by the European Union and Medical Research Council has yielded promising results from new drugs which selectively target minute quantities of the foul smelling gas hydrogen sulfide inside blood vessel cells. Research indicates the drugs AP39 and AP123 could help prevent sugar (glucose) from damaging endothelial cells, which line blood vessels and form an interface that regulates the exchanges of materials such as oxygen and food metabolites between blood and surrounding tissue.

      People with diabetes have an excess of glucose in their blood (hyperglycaemia). This leads to the mitochondria, the “power house” of the cell which normally regulates energy production and use inside cells very tightly, becoming inefficient and leaky. They then produce highly toxic metabolites of oxygen (free radicals). The resulting toxicity to the mitochondria in the endothelial cells damages blood vessels in the circulation and the heart. This can deprive organs of the blood they need to function, potentially resulting in kidney disease or retinopathy, which cause blindness. Around 1,280 cases of blindness causes by diabetes each year in England alone, with a further 4,200 people identified as at risk of vision loss from this cause. Damaged blood vessels can also contribute to kidney disease, which can affect up to one in three people with diabetes.
      Now, research using endothelial cells isolated from the small blood vessels in the brains of mice has revealed that carefully targeting minute quantities of hydrogen sulfide to the mitochondria inside cells using AP39 or AP123 restored the efficiency of the mitochondria and prevented hyperglycaemia-induced build up of free radicals. The team found that the effects of the drugs were long-lasting, suggesting that they could help to treat heart problems and blood vessel complications that occur in the heart, kidney and eyes of people with diabetes.

      Professor Matthew Whiteman, of the University of Exeter Medical School, who led the study, said: “We’re producing a growing body of evidence that hydrogen sulfide can have a range of health benefits, when carefully administered in minute doses in a highly targeted way in the body. Mitochondria can even make their own hydrogen sulfide and use it as a ‘fuel’ to keep metabolism efficient. When this ‘fuel’ is lost, mitochondria, cells, blood vessels and tissues are damaged. We previously showed that replacing the lost hydrogen sulfide with AP39 reversed this damage in cardiac arrest, hypertension and kidney failure damage and this current study adds AP123 to our portfolio of promising new drugs for diabetes.

      “Some people find it amusing that a substance with such a bad reputation can produce these benefits, but nearly every cell in our body makes and responds to tiny amounts of hydrogen sulfide and we have at least three distinct pathways for making this gas in very small quantities so it is very important. We must now continue working hard towards taking our findings forward in humans”.

      The paper, ‘The novel mitochondria-targeted hydrogen sulfide (H2S) donors AP123 and AP39 protect against hyperglycemic injury in microvascular endothelial in vitro’ is published in Pharmacological Research. Authors are Domokos Gerö, Roberta Torregrossa, Alexis Perry, Alicia Waters, Sophie Le Trionnaire, Jacqueline L. Whatmore, Mark Wood, Matthew Whiteman.
      Date: 1 September 2016

  39. Mike Wroe

    I am still troubled and unable to understand. If the endothelium is damaged (for whatever reason) and the formation of blood clots is the means that the body uses to repair the damage why use blood clotting reducing agents. Surely this delays repair. And when the body’s resources have repaired the damage why does the blood clotting persist and result in plaque formation?

  40. Errett

    Tryptophan — commonly associated with turkey — is a normal part of the mouse and the human diet. Protein-rich foods contain appreciable amounts: nuts, eggs, seeds, beans, poultry, yogurt, cheese, even chocolate.

    When the researchers doubled the amount of tryptophan in the mice’s feed, the number of such cells rose by about 50 percent. When tryptophan levels were halved, the number of cells dropped by half.

    “The development of these cells is probably something we want to encourage since these cells control inflammation on the inner surface of the intestines,” Cervantes-Barragan said. “Potentially, high levels of tryptophan in the presence of L. reuteri may induce expansion of this population


    1. Gary Ogden

      Errett: Thanks for the link. That university is doing some very interesting research into the gut microbiome and its relationship to health and disease. In my opinion, these critters are the most important key to our health, but, of course, such emerging knowledge is ignored by industry spokespeople such as Steven Nissen, and by mainstream dietitians as well.

    2. Andy S

      Humans with irritable bowel problems might not benefit from consuming more turkey sandwiches. Moue studies were good but studies using humans are needed.

    1. Andy S

      Insulin resistance is not technically a culprit, it would be more accurate to call it a metabolic abnormality caused by chronic overconsumption of carbohydrates. Chronic Metabolic Overload?

  41. Luis

    In Argentina, Lilly (Cyalis) has been allowed to sell the 5 mg tab. and not the 2.5 mg one, which is what they recommend as a staring dose, the tab in enterically coated, so they tell you not to split it…corruption anyone? Be that as it may, at 76, I have been splitting them and aside from the erection effect which is mild but noticeable, it also produced an improvement of prostatic symptoms, decreased the number of times I have to get up to pee at night

  42. Bill In Oz

    Dr Kendrick, can I suggest that the way that the comments & replies are organised be improved ? At the moment replying to a comment is difficult as it is hard to find the original comment. I have tried but it means trawlling through the whole bloody lot. That’s a waste of time.

      1. Martin Back

        Your level of nesting seems to be set at the default level of 3. If you were to increase it to 4 I think it would help. I wouldn’t go any higher that 4 though. It tends to squeeze comments into ever-narrower columns.

    1. barbrovsky

      Re Commenting:
      Yes agreed! It really is irritating. I’ve been using WordPress for nearly 10 yrs, although this is a WordPress-hosted site which makes a difference in how they can be configured. Ideally, when you respond to a comment via the email link, it should take you to a dialogue box immediately after the comment or post, and I think it’s here that the problem exists. Is it a response to the post or to the comment? So WP assumes it’s to the post, which is why you end up at (often) a lot of comments! Perhaps it’s this particular WP theme wot does it?

    2. Antony Sanderson

      Bill – I tend to start from the email notification . . . If I want to see where the comment fits in with the blog I . . .
      Highlight a small section in the comment on email . . .
      CNTRL C to copy
      Click to the blog (on a separate tab)
      CNTRL F to get up the find box
      CNTRL V to copy the highlighted text
      It will jump to the comment.
      You then just have to scroll back up a couple of comments to the originating one.

      Again, if you want to find a comment you have made . . . just CNTRL F and type in a bit of your name . . . Enter/Return . . . Then just click through each comment you made.

      1. Bill In Oz

        Anthony, I have been trying to start with the email notification also. I am using an Apple desk top ( 5 months old ) I will give your suggestion a try with the next reply I make. But maybe Dr Kendrick can change the level of nesting from 3 to 4….I am a complete ignoramus with computers but In other blogs where I make comments, this seems to work..Though the type box area does get narrower.

  43. Bill In Oz

    Somebody made the comment “obese Mice” in response to my discussion/comment about Chondoitrin sulfate. No link or anything else.

    What do you mean ? Why do you make this remark ? By itself it is meaningless.

    1. Gary Ogden

      Bill in Oz: Sorry for the cryptic nature of my comment. The study you referenced was done on obese mice, not humans. The results may very well have implications for humans, and I suspect they do, but the distinction matters. I very much appreciate all of your input here.

      1. Antony Sanderson

        Bill . . . Loved the paper

        I have been taking a chondroitin sulphate/glucosamine supplement for 20 odd years. Originally because I had inflammation/pain in the ankles. A colleague said the preparation had helped her back issues. I tried it, the problem with the ankles went away . . . whether chondroitin or the glucosamine was to be thanked, or whether time was the healer I do not know. . . . however . . . I still continue to take it on a daily basis because I have discovered that if I do not take it regularly then my finger nails are prone to break. This is a pain (not the right word) – inconvenience for a finger-picking guitar player. If I stop taking the tablets then within the month . . => broken finger nails.

        Chondroitin or glucosamine at work on my fingernails . . . ooo. . . I feel an N=1 project on the horizon.

      2. Martin Back

        I knew someone who played Spanish guitar. He used to eat ProNutro to keep his fingernails strong. ProNutro was originally formulated as a cheap high-protein meal for refugee camps and the like, but proved too expensive for that purpose and is sold as a breakfast cereal in South Africa. For your research project, maybe you could compare the ingredients with chondroitin and find the common factors.

      3. Bill In Oz

        Martin I see that “pronutro’ is 19 grams per hundred sugar – almost 5 teaspoons ! I doubt that this is very health inducing !

      4. Martin Back

        I’m only reporting that ProNutro appears to make strong fingernails. Personally I ate masses of the stuff in my younger days, believing that it was healthier than corn flakes or rice krispies, but now I believe that the healthiest breakfast is no breakfast.

    2. Antony Sanderson

      Martin, . . . had a look at the nutrients of ProNutro . . . the Glycaemic Carbohydrate of 54g in 100g is a bit high for my present regime . . . so it looks like I will be buying pure chondroitin . . . have a wash-out period of about one month or until the first nail cracks/spilts/breaks . . . take the pure chondroitin for a couple of months and see if nails harden.

      But what about the chondroitin dose?. Do a keep to the same as in the chondroitin/glucosamine combo (0.8g/day) . . . should do really.

      The above chondroitin paper that Bill (of Oz) referenced, looking at reducing secondary coronary events, has people starting on 10g/day for 3 months, dropping to 1.5g a day for 4 and half years, 0.75g for a couple more years.

      Their study was an RTC trial on patients with CVD – conducted over 6 years . .

      Reported results . . .

      60 patients received oral chondroitin sulfate A (GSA) daily for 6 years with conventional treatment.
      60 patients received no CSA but comparable conventional treatment over the six year period.
      Six coronary incidents in CSA treated group were observed as compared to 42 in non-GSA treated patients
      . . . a ratio of 6:42.

      4 fatal myocardial infarctions were observed in the CSA treated group of patients as compared to 14 fatal myocardial infarctions in the control, non-C-SA treated patients;
      A ratio of 4:14 for cardiac death rate.

      On the face of it I think the chondroitin had a better success rate than statins . . .

      Taking a leaf out of the big pharma statistics guide . . .
      Cardiac incidents (probabilities) . . . intervention arm 10% . . . . control arm 70%
      Difference 60%
      Relative risk reduction . . . 60/70*100 = 86%

      Worth another look?

      1. Bill In Oz

        Anthony, you have summurised the Morrison research 1973 paper quite well. I first found a link to it in early June and was astonished that it had been completely overlooked in mainstream medicine.

        It beats all the results of trials for anything else hands down.

        I also immediately sought out some CS locally. None of the chemists or health food shops had any. So went online and wound up,ordering a brand called “Now” CS with 600 mg of CS in each capsule from Iherb. As I found other sources online about CS I became more convinced. So I then ordered enough containers for 3 months at 10 grams a day.. Roughly 16 capsules a day. I will step down to 1.5 grams in mid September.

        I have wondered what happened that CS and Morrison’s work was lost for so long. What I do know is that after the 1973 research paper he did not publish anything else that I can find. He retired shortly afterwards and then died in 1991 aged 84. Maybe he simply retired at the wrong time.

        What with CS not being under patent there is no real way for pharmaceutical companies to make a fortune from selling it.

  44. Charlie

    Interesting study on the role of glucose on platelet activation:
    Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function


    “In conclusion, these studies reveal an essential role for glucose metabolism in regulating multiple facets of platelet function, including platelet activation, thrombosis, platelet production, and clearance from the circulation. Elucidating the fundamental roles of glucose metabolism in platelets provides the conceptual framework to better understand how the extracellular milieu could potentially alter platelet function in metabolic disorders such as diabetes, where dysfunctional Ca2+ signaling is a hallmark of platelet dysfunction.”

  45. Bill In Oz

    @Martin Black re “the tetraethyl lead molecule” Ummmm yes I think it would do significant damage. However here in Australia leaded petrol was phased out in 1990. It has not been available for sale ever since,. That’s 27 years. Yet CVD is still a major cause of death. I imagine that the USA, UK, Germany, and other western countries have also phased it out. So I think it doubtful that leaded petrol is a major factor in heart disease in such countries now.

    1. Martin Back

      Leaded petrol has been phased out in South Africa as well. But the death rate from CVD in the western world was much higher in the 1960s than it is now, something which epidemiologists have never been able to explain definitively, although there are plenty of theories. Could leaded petrol be one of the causes of higher CVD rates then? I don’t know, but it is on my list of suspects.

      1. Bill In Oz

        Martin I thought that the drop in the percentage of smokers in the population was/is a major reason…Which I guess leads me to ask if the percentage of smokers has dropped in South Africa and has there been a measurable drop in heart disease rates ?

        I’ve also been pondering Dr Kendrick’s thesis ( as of 2008 in his book ) that the stress brought on by social, economic & political instability is directly correlated to CVD rates. The examples in Finland post 1948, Russia, Latvia, Estonia, etc post 1990 are very marked.

        And Dr Kendrick, I wonder what happened vis a vis CHD rates in the former Easter Germany after it collapsed and became part of a united Germany in 1990. West German ‘wealth’ was used abundantly then to ease the transition .. But what happened as regards CHD rates ?

      2. William Bowles

        Re Easter[n] Germany etc and CVD:

        Hmmm… I thought Kendrick’s book ‘The Cholesterol Con’s’ conclusions re stress pointed directly to exile/uprooting, so I don’t think the former GDR falls into that category, unless you assume that the reunification was a form of exile (from the GDR)? I thought the exile paradigm was pretty clear: exile leads to stress, stress leads to heart disease, at least in those already prevalent?

      3. Dr. Malcolm Kendrick Post author

        I think this is a very complex area. After the fall of the wall in 1989, CVD deaths shot up in most ex-Soviet countries (to a great or lesser extent). Lithuania and Latvia experience the sharpest rise. Poland much less so. Romania and Hungary were hardly affected at all. Not until Gorbachov was toppled by Yeltsin did the CVD rate shoot up in Russia (in 1991). I have not ever looked at East German CVD rates after 1989. I am not sure they exist in isolation from the rest of Germany – perhaps someone has these figures, I think they would be interesting. I suspect unification with West Germany would would been a relatively positive step for most (if not all) residents of East Germany. So my, tentative, prediction would be for little immediate change in the figures. Unlike, say, Lithuania where death from CHD rose almost 100% over the following five years.

      4. William Bowles

        Yes, I think the former USSR especially would be an interesting area to test the stress theory. Total social, economic and political fragmentation; destruction, almost overnight, of social structures that had been extant for over 70 years. The welfare state vanished, life expectancy plummeted. Unheard of before, unemployment. Millions unemployed. If that wasn’t a total stressed out environment, I think you’d have to go the Occupied Territories in Palestine, to see something comparable, stress-wise. BTW, has anybody done (bothered to) surveys of the captive Palestinian population?

      5. Gary Ogden

        William Bowles: Congenital heart disease in 1% of live births seems high. I wonder how this compares with other populations.

      6. William Bowles

        Gary: I suspect that the environmental conditions are so awful in the Occupied Territories (lack of clean water, poor to devastating nutrition, the stress of living under Israeli occupation, where even movement is regulated from street to street with roadblocks and so, that health, normal health that is, is entirely absent, so it doesn’t surprise me at all.

      7. Gary Ogden

        William Bowles: Yes, it is an unthinkable tragedy. The Middle East is a tragedy created by the battle between U.S., British, and Russian petroleum interests early in the 20th century. Governments care not a whit for the health and well-being of their subjects, or anyone else, because all governments work for industry, and there is no profit in health, or culture, or joy.

      8. Bill In Oz

        Thanks Dr K. That was my intuitive guess as well. ‘That the decision by West Germany to use it’s wealth to ease the pain would have helped.” But there was also a lot of unemployment immediately after the reunification and could have been health effects from this I suspect.

      9. Bill In Oz

        The heart disease rates in Russia, Poland and the Baltic states all spiked after the Soviet Union collapsed in the early 1990’s. Massive social, economic & political disruption. And Dr Kendrick points out that there was a huge increase in CHD. It’s not just being forced into exile as happened in Karelia in Finland in 1948.

      10. Martin Back

        Dr David Grimes considers many possible factors and concludes that a micro-organism was the cause of the “epidemic” of CVD in the previous decades. I keep an open mind on the question. http://www.drdavidgrimes.com/2016_07_01_archive.html

        Personally, I feel there are so many confounding factors when considering stress at a national level that no conclusions can be drawn as to the effect on CVD. Not to mention the drop in CVD during stressful times such as under Nazi occupation.

        ‘Although stressors trigger events, it is less clear that stress “causes” the events. There is nonetheless overwhelming evidence both for the deleterious effects of stress on the heart and for the fact that vulnerability and resilience factors play a role in amplifying or dampening those effects.’ — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633295/

        When you consider that CVD can be reliably induced in experimental animals by diet alone, e.g. by feeding guinea pigs a diet with no vitamin C, or feeding primates a typical Western diet, I feel that you need some very powerful evidence to propose a non-dietary cause.

      11. Bill In Oz

        Martin you said ” feeding guinea pigs a diet with no vitamin C, or feeding primates a typical Western diet” leads to CHD..

        Ummmmm…..In order to feed primates this diet, they are confined in a research lab with no capacity to lead natural lives…Now that would be stressful I suggest. Ditto for Guinea pigs…

        And perhaps feeding these animals such a ( for them ) unnatural diet, does not trigger stress in it’s own right….

      12. Martin Back

        Guinea pigs and primates fed an appropriate diet don’t get CVD, despite also being kept in cages. So it appears that the diet makes the difference.

      13. Dr. Malcolm Kendrick Post author

        I think the central point of my extended series on CVD is to try and make it clear that there is no single cause. Or, in most causes, no single cause. The guinea pig example makes it clear that an extreme vitamin deficiency can, on its own, do massive damage – quickly. However, in most cases there is a combination of things going on.

      14. Antony Sanderson

        Dr K: “I think the central point of my extended series on CVD is to try and make it clear that there is no single cause.”

        This is exactly where I have got to. You hear one proposed idea for the cause of heart attacks, then another, and yet more again. Each one has its plus points, but at the same time each seems to have events it cannot explain or do not fit in. For example: Heart attacks caused by blood clots . . . ah yes, but some heart attacks do not seem to involve blood clots . . . And so it goes on.

        It is a bit like focussing on “the reason we have car engine breakdowns” and insisting there needs to be a single all-encompassing explanation. We know enough about cars to know that it could be the electrical system, the engine control module that has given out, a blockage in the fuel line, a lack of oil . . . and so on.

      15. Dr. Malcolm Kendrick Post author

        Anthony, there are at least seven different versions of a ‘heart attack’ that I am aware of. The most common is the classical, blood clot over atherosclerotic plaque > obstructed coronary artery > infarction. However, you can have infarction with no blood clot MINOCA. You can have tako-tsuba (stress induced heart muscle damage), you can have sudden death syndrome, or acute asystole due to hypertrophic cardiomyopathy. Or you can have blot clot > myocardial infraction (up to several weeks after the clot has formed). You can also have sudden development of a blood clot > infaction with no underlying arterial disease. There are others, but these will do for now. However, it is still rare to have a ‘heart attack with no underlying arterial disease. In my view MINOCA (myocardial infarction with non obstructive coronary arteries) is almost certainly due to the sudden development of a blood clot – that has been broken down, and is gone, by the time anyone manages an angiogram. How can I prove this – I can’t. It is difficult to prove the existence of something that is gone by the time you look for it. It can only be inferred through logic. One many find evidence of a lightening strike in the absence of lightening.

      16. chris c

        It may have been banned but I wonder for how long it continues to lurk in the environment? Maybe a slow decrease?

        Yes it’s a bit odd how CVD spiked and started to decrease BEFORE low fat diets and statins were invented, eh?

      17. Bill In Oz

        Chris, you are right and you have jogged my memory..

        many years ago a friend worked for CSIRO here in Australia on lead contamination.. He also bought a new house while there at CSIRO. And like me was a keen gardiner. His newly purchased house was in a side street 100 meters off a major 6 lane arterial road. As a matter of interest he took soil samples and measured the lead content. It was so high he decided to bring in new soil from elsewhere and create raised beds.

        As he explained all the lead in petrol does not disappear when burned. It is a heavy metal and quickly settles out of the air in the air onto the grass and soil. So indeed every gram of that lead burned in petrol is still lurking about.- concentrated especially close to major roads. The question then becomes how much is taken up by plants and into food crops. If the soil is very acidic, this happens a lot. So don’t grow food gardens close to major roads even if there is no leaded petrol now..The lead will still be in the soil from decades ago when leaded petrol was used.

        It also helps if the soil is ph 6 to 6.5 with a high organic carbon content as this helps prevent lead being taken up by the roots of garden food plants.

        By the way, this is one reason why organic farms tend to be off major roads and freeways – at least here in Australia.

        So I need to retract my earlier comment about lead no longer being around as we don’t burn leaded petrol anymore. It’s still around even in countries where leaded petrol is now banned.

        I wonder what the epidemiology would show if CHD patienst were screened /filtered by the type of road/street they lived on.

    2. Bill In Oz

      We have been discussing how massive social changes lead to increased CHD in the countries of Eastern Europe. But tToday in New Scientist here was a report about Northern England compared with Southern England.
      ” By New Scientist staff and Press Association

      People in northern England are 20 per cent more likely to die before the age of 75 than those in the south.

      Iain Buchan, of the University of Manchester, UK, and his colleagues analysed Office for National Statistics death data from 1965 to 2015, dividing England into two regions. The northern region also included the midlands, while the southern region included East Anglia.

      They found that, since the mid-1990s, the number of deaths among people between the ages of 25 and 44 have been rising. In 2015, there were 49 per cent more deaths among 35 to 44-year-olds in the northern area than in the south, and 29 per cent more deaths among 25 to 34-year-olds.

      “Five decades of death records tell a tale of two Englands – north and south – divided by resources and life expectancy,” says Buchan.

      The study didn’t look at the causes of death, so could not identify what was causing the rise in premature deaths in northern England. However Buchan suggests that economic and social factors underpin these early deaths, and solving this will require a rebalancing of the economy

      Journal reference: Journal of Epidemiology & Community Health, DOI: 10.1136/jech-2017-209195″

      I guess being a doctor in Cheshire the past few decades would have provided you Dr Kendrick with your own personal perspective of this.

      1. Martin Back

        Southern England gets more sun than Northern England. Control for that before blaming economic and social factors for any health differences.

      2. Dr. Malcolm Kendrick Post author

        Martin, you appear very set against social or economic factors playing an important role in health/CVD. You may find this report of interest. It controls for sun, in that the report pirmarily looks at Glasgow. There is a gap of at least 11 years between more affluent and deprived areas of Glasgow.

        “Life expectancy in Glasgow

        In 2016 we published Glasgow: health in a changing city. This report describes life expectancy trends in Glasgow since the early 1990s and tracks changes in neighbourhood-, deprivation- and gender-related health inequalities. The report also describes the changes in population, housing, environmental and socioeconomic circumstances within the city.

        The analysis shows that despite improvements in life expectancy for men and women in the last fifteen years, life expectancy in Glasgow remains significantly lower than in Scotland with no sign of a narrowing of this gap relative to Scotland.

        The findings also point to the persistence of the health gap between our most deprived and affluent communities and show that the gap in female life expectancy between our most and least deprived areas has widened to nearly eleven years. In addition, there has been a relatively poor trajectory for female life expectancy compared to males over recent years, particularly in the most deprived half of Glasgow.

        The life expectancy indicators used in this report are also presented in the health section of the Understanding Glasgow website. In addition, there are two sets of neighbourhood profiles for Glasgow: a set that cover the whole population which were first published in 2014 and a set of children and young people’s profiles which were published in December 2016. Both sets of profiles include indicators of health and wellbeing at three geographic levels: Glasgow as a whole; three sub-sectors of the city (North East, North West and South Glasgow); and 56 neighbourhoods across the city.

        Comparisons of aspects of Glasgow’s 56 neighbourhoods is a statistical report that complements the aformentioned publications. In it data from the census and other sources are used to compare demographic, socioeconomic and health changes across Glasgow’s neighbourhoods. The indicators shown include population measures, life expectancy, car ownership, overcrowding and vicinity to vacant and derelict land. The main comparison periods used were 2001 and 2011.

        Life expectancy in Calton

        A by-product of the aforementioned analysis is that up-to-date estimates of life expectancy in Calton & Bridgeton have been produced. These new estimates challenge the oft-quoted statistic that life expectancy in Calton is 54 years – a figure that is misleading and out of date. Our more recent estimates are that, in 2008-2012, male life expectancy at birth was 67.8 years in Calton & Bridgeton, while female life expectancy was estimated at 76.6 years.

        For further discussion of this topic, see this blog post: Life expectancy in Calton no longer 54″. http://www.gcph.co.uk/work_themes/theme_1_understanding_glasgows_health/life_expectancy_in_glasgow

      3. William Bowles

        No sun in the North? That’s utter nonsense! All studies show that the north of England is deprived in comparison to the South. Worse nutrition, greater unemployment, worse housing conditions, need I go on? O don’t think so.

      4. Bill In Oz

        Martin I cannot speak for the difference in sun light between Southern & Northern England – even though I was born in Bootle in Liverpool. My family migrated to Oz in 1952 when I was four. Lack of sunlight is hardly ever a problem here. However Australian CHD rates are up there with the UK & USA.
        Also aging does lesson the capacity of the skin to utilise sunlight to make Vitamin D3. So now I take lots of Vitamin D3 along with K2 each day.

      5. David Bailey


        I don’t think you would talk as you do, if you had actually experienced severe economic/social conditions. Imagine for a moment being on two (or even more) very low paid jobs, trying to keep your family in food, and pay the rent.

        Everywhere you turn you would find invitations to gamble or drink what money you have, and some people just can’t resist temptation.

        People get into debt – often with illegal lenders who have their own highly stressful ways to enforce payment, etc.

        Now imagine what all of that stress does to the body – perpetual stress, day in, day out.

      6. Martin Back

        Sunlight is a major factor in health, see e.g. Dr Malcolm Kendrick “Sunbathing is good for you” or Dr David Grimes “Belfast, Toulouse, and the Sun” and “The importance of the sun – more experience from Lancashire UK”, and Northern England indubitably gets less of it than Southern England.

        I can’t deny that poor people and regions have worse health than wealthier people and regions. But why? That’s the interesting question. And for that you have to compare apples with apples. A blanket statement such as “the north is worse than the south” tells you very little from a health point of view because there are so many confounding factors.

        I am aware that from a political point of view in England “North vs. South” is a loaded comparison, usually preparatory to blaming the ogress Maggie Thatcher and the Conservatives for all the North’s troubles. Unfortunately for those people, I lived in England pre-Maggie Thatcher and saw how bloody-minded behavior by unionised workers caused the destruction of the Northern industries, so the argument doesn’t impress me.

        Getting back to health, people in sunnier climes have better health because they get more vitamin D. After controlling for that, if there is an unexplained residual health difference, you have to look further. What about the number of doctors and hospital beds per 1,000 population? The number of cubic feet of air in their housing? On and on. Try and tease out the factors. Then figure out what the authorities can do something about, and what they can’t.

        Generally you’ll end up with factors like unemployment, risky behavior, drugs, cigarettes, alcohol, and a generally bolshie and self-destructive attitude that authorities can’t do anything about. Of which unemployment is probably the most important, leading to broken families, poor nutrition, and badly brought up children.

        On the nutrition front, I shop in a lower middle- to working-class area and I see what people put in their shopping baskets. It is horrifying the amount of sugary cool drink and packaged junk foods they buy. Virtually no fresh foods or anything that needs preparation. And I know from my own experience this type of diet leads to behavioral issues, something I believe has been confirmed in prison studies.

      7. Dr. Malcolm Kendrick Post author

        Martin. Of course, I agree that sunlight/vit D is an important factor in health. However, at one time, Australia had a very high rate of CVD, as did South Africa. As for social factors, and psychosocial stress. Per Bjorntorp did some fascinating work in this area. As has Michael Marmot. Of course, those in lower social classes tend to have grouped ‘ill health’ behaviors. From smoking, to drinking, poor diet, increased drug use etc. But even if you control for these factors, life expectancy is lower. You should look up Marmot’s Whitehall study. A very clear link between social ‘status’ in the workplace and health – or ill-health. Perhaps the most dramatic example is Australian Aboriginals.

      8. Sylvia

        But since Mrs Thatcher said ” Let the market decide” this did indeed create an even greater inequality amongst people’Yes, socioeconomic matters play a large part in the health of people. The wealthier have better nutrition, better housing, more expensive clothing and in the south of England where investment is greater more employment.
        Lower income families in deprived areas live in inferior housing, perhaps in fuel poverty, their groceries will be simply what they can afford. many families work wonders, this is the north of England I recognise, having worked as a district nurse the last ten years before retirement, in a deprived area. What can I say, Crossrail, garden bridges, commonwealth conservatories.
        Martin, we get sunshine, trust me it is not lack of Vit D. Hope this is not too political Dr Kendrick. Forgive my rant Martin. And please excuse my sentence structure and punctuation,can’t seem to master it with typing.

      9. Bill In Oz

        Dr Kendrick, you have mentioned Australian aboriginals a couple of times. I am not personally familiar with their plight as I live in an area which has few aboriginals. From what I have read, it is true that the Aboriginal people have a higher risk of CHD. And that their diet has changed substantially over the decades towards a high sugar, carbohydrates and processed food diet.

        But there are lots of confounders : smoking, alcohol, petrol sniffing, drugs and obesity. All this on top of the stress that comes with living in remote & isolated disfunctional communities with high rates of unemployment.

        ( Recently there have been demands from Aboriginal community members in remote areas, that they have a ‘right’ to employment even though there is no industries to generate any employment. But that is a different issue. )

      10. Dr. Malcolm Kendrick Post author

        I could also have mentioned NZ Maoris, or native Americans (american aboriginals), or the Inuit. Indigenous populations in territories colonized/taken over by ‘outsiders’ generally tend to do very badly indeed. As their social structure break down, they die. This is also, usually, true of emigrant populations. In most cases emigrant population fare very badly, health wise. Exceptions to this rule include the Roseta community of Pennslyvania.

        To quote:

        It seemed like a virtual fountain of youth, with a heart attack mortality rate roughly half the rate of every surrounding community. Same water, same neighborhood, same occupational mix, same income level ranges, same races. So what was the difference and why?

        Well, you had to ask the Rosetans for the answer, and the next question you ask should be, Who are the Rosetans?

        The Rosetans are inhabitants of Roseto, Pennsylvania, a pretty but remarkably modest village nestled in Eastern Pennsylvania. Back in 1962, in a scene out of the movie Outbreak, investigators descended on Roseto with the full equipment of scientific investigators…with the blessings of the Federal and State governments. Roseto was a starkly healthier place to live, and no one could guess why. It was up to these researchers to figure out why, and they stayed for several years.

        Pouring over death certificates from 1955 until 1965, the investigators concluded that the reason was unusually clear for science. Just to make sure, the Rosetans were compared with neighboring communities, including the aptly named “Nazareth” and “Bangor” towns. The confirmations just kept on showing up in everything the researchers did. And the conclusions have had tremendous implications since they were confirmed in 1992.

        What made Rosetans die less from heart disease than identical towns elsewhere? Family ties. Another observation: they had traditional and cohesive family and community relationships. It turns out that Roseto was peopled by strongly knit Italian American families who did everything right and lived right and consequently lived longer.

        In short, Rosetans were nourished by people.

        In all ways, this happy result was exactly the opposite expectation of well-proven health laws. The Rosetans broke the following long-life rules, and did so with a noticeable relish: and they lived to tell the tale.

        They smoked old-style Italian stogie cigars, malodorous and remarkably pungent little nips of a cigar guaranteed to give a nicotine fix of unbelievably strong potency. These were not filtered or adulterated in any way.

        Both sexes drank wine with seeming abandon, a beverage which the 1963 era dietician would find almost prehistoric in health value. In fact, wine was consumed in preference to all-American soft drinks and even milk.

        Forget the cushy office job, Rosetan men worked in such toxic environs as the nearby slate quarries. Working there was notoriously dangerous, not merely hazardous, with “industrial accidents” and gruesome illnesses caused by inhaling gases, dusts and other niceties.

        And forget the Mediterranean diets of olive oil, light salads and fat-free foods. No, Rosetans fried their sausages and meatballs in…..lard. They ate salami, hard and soft cheeses all brimming with cholesterol…. etc. http://www.huffingtonpost.com/dr-rock-positano/the-mystery-of-the-roseta_b_73260.html

      11. Bill In Oz

        The example of Rosetto is powerful. And I wonder if the Kitava Island in Papua New Guinea, are yet another example. All the discussions I have read so far emphasises their diet as the major reason for their low CHD. But Kitava is an isolated Melanesian island with a close knit community life with 3 generations haring homes and life together..

      12. David Bailey

        To me the stress explanation of CVD is particularly plausible, because if CVD is mainly the result of stress, then researchers looking for a physical cause will be sent skittering down all sorts of blind alleys. People under stress will inevitably behave somewhat differently – eat different diets on average, maybe get less sunlight in some circumstances, but more in others, suffer more exposure to industrial chemicals etc.

        In other words, if people ignore stress as a direct explanation when it is the true cause, they will see lots of other secondary lifestyle correlations that will lead them astray – and that is exactly what seems to have happened.

      13. chris c

        Wow, more fascinating thoughts!

        I also ponder genetics which are more resilient to epigenetic changes. One side of my family emanated from Suffolk several generations back – according to family legend they moved to “a small village near London called Notting Hill” and then to Surrey and Sussex. In more recent times a number of us returned to Suffolk.

        To my knowledge my mother was the record holder, living to 95, her own mother to 90 and the youngest female died at 82. Not uncommon ages locally looking in the churchyards – a neighbour was 108 1/2. Males not so lucky, we often die before 70, almost certainly a result of this weird type diabetes. OTOH NO-ONE in this line EVER had cancer. Tell that lot to an Evidence-Based doctor and they would say you were making it up.

        Local access to Real Food and relatively low stress are probable factors too, judging by the increasing size and decreasing health among the young here compared to their parents and grandparents I suspect we are tending towards a norm.

  46. Bill In Oz

    @Dr Kendrick, I have just finished reading your book The Cholesterol Con that you wrote in 2008. The chapter towards the end of stress being the cause of heart disease is I think largely accurate.. Stress damaging the HPS axis, causing elevated cortisol and thus hypertension and damage to the endothellium, seems well presented to me.

    I read your post n Mid July where you suggested that the jig saw peices needed refitting. But really I could not find much to fault it..

  47. Errett

    Exercise works wonders—25 mg of DHEA helps also—

    Walking training and cortisol to DHEA-S ratio in postmenopause: An intervention study
    Andrea Di Blasio , PhD, Pascal Izzicupo , PhD, Angela Di Baldassarre , MD, Sabina Gallina , MD, Ines Bucci , MD, Cesidio Giuliani , MD, show all
    Pages 1-16 | Received 07 May 2016, Accepted 24 Feb 2017, Accepted author version posted online: 22 Mar 2017, Published online: 22 Mar 2017
    Download citation http://dx.doi.org/10.1080/03630242.2017.1310168

    The literature indicates that the plasma cortisol-to-dehydroepiandrosterone-sulfate (DHEA-S) ratio is a marker of health status after menopause, when a decline in both estrogen and DHEA-S and an increase in cortisol occur.

    An increase in the cortisol-to-DHEA-S ratio has been positively correlated with metabolic syndrome, all-cause mortality, cancer, and other diseases.

    The aim of this study was to investigate the effects of a walking program on the plasma cortisol-to-DHEA-S ratio in postmenopausal women.

    Fifty-one postmenopausal women participated in a 13-week supervised walking program, in the metropolitan area of Pescara (Italy), from June to September 2013. Participants were evaluated in April–May and September–October of the same year. The linear mixed model showed that the variation of the log10Cortisol-to-log10DHEA-S ratio was associated with the volume of exercise (p = .03). Participants having lower adherence to the walking program did not have a significantly modified log10Cortisol or log10DHEA-S, while those having the highest adherence had a significant reduction in log10Cortisol (p = .016) and a nearly significant increase in log10DHEA-S (p = .084).

    Walking training appeared to reduce the plasma log10Cortisol-to-log10DHEA-S ratio, although a minimum level of training was necessary to achieve this significant reduction.

  48. Martin Thomason

    For those of us who have been unfortunate enough to have suffered a heart attack – the bog standard response to aftercare is:

    Aspirin (prevent clots)
    Beta-blocker (slow the heart down)
    Blood pressure med’s (to lower it)
    Statins (to lower that cursed cholesterol)

    This, I’ve been told will be the case for the rest of my life.

    A couple of questions if anyone has answers …….

    Aspirin – I read something (now unable to locate it) that this interferes with, and robs cells of their Vitamin C content, this doesn’t sound good when Vit’ C is so important ?

    Beta-blocker – what is the necessity to remain on these if the heart rate was never high in the first instance – are they beneficial generally for heart health ?

    Blood pressure med’s – again if a person’s blood pressure wasn’t high to start with, is there any benefit to continuing taking these ?

    Statins – if they are beneficial from the point of view of increasing nitric oxide from the endothelium, how does this balance against the shortened lifespan linked with low levels of cholesterol ?

    A sincere thank you for your help


    1. William Bowles

      I take Vit C (and an Aspirin) every day but actually didn’t know that Aspirin reduces vit c.

      Yes, I was put on beta blockers, though like you, I didn’t have a high heart rate (65-70 normally). In fact I had an ‘adverse reaction’ to the beta blocker (Bisoprol Fumarate) without realising it was the cause, until a consultant asked me why I was taking them if I didn’t have angina? I stopped them and all the growths on my head and feet promptly disappeared!

      BP: Well I’m still taking Ramipril, though my BP ain’t high normally (128/81)

      Gave up statins 3 yrs ago but take concentrated Beetroot instead.

      I also take B12 and Vit D3/K2 every other day.

      But I think just as, or maybe even more, important is diet. So cut the sugar down as much as possible and don’t eat processed food. I have a mainly fresh food diet, with low carbs (I have potatoes, noodles or rice occasionally, a slice of toast with my breakfast). I think the only other source is the natural yogurt (no sugar) I have with fruit (berries mostly.

      1. Gary Ogden

        Sasha: Also, according to Kauffman (Second International Study of Infarct Survival, 1998), “Hence all of the survival benefit from an early, one-month course of oral aspirin (162.5 mg enteric coated, daily) seemed to accrue during the first month, with little further benefit between day 36 and the end of year 10, by when the death rate was down 1% absolute relative to placebo [from 22% in the first month] (Baigent et al, 1998).

    2. Gary Ogden

      Martin Thomason: You will find an abundance of answers to all these questions in “Malignant Medical Myths,” by Joel Kauffman, PhD. Sample quote:
      Aspirin: From Duane Graveline, M.D. “. . . we are indebted to Kauffman’s suggestion of such aspirin substitutes as oils with omega 3 fatty acids, coenzyme Q10, magnesium, and even vitamin E, all of which address inflammation or other aspects of heart health at least as effectively as aspirin, if not more so, and they do so with near absence of side effects.”
      I highly recommend this book. In my case the beta blocker proved to be dangerous. Seemed every time I got up from squatting in the garden, I nearly fainted. ACE inhibitors for hypertension appear to have some benefit, with fewer adverse effects, but beta blockers are hard to justify, in my opinion. And I haven’t seen any compelling evidence for BP drugs in the normotensive, although there may be in secondary prevention. Dr. Kendrick has already covered statins from soup to nuts, so read all of his blog posts and “The Great Cholesterol Con.”

      1. Kathryn Bosse

        Thank you for the information about the book “Malignant Medical Myths. Beta Blockers and Ace inhibitors are not good for me either. My Doctors seem to be mystified by it, But, I keep saying NO, NO, I will not take them. They just do not work right for me.

      2. Martin Thomason

        Thank you all (Gary, Sasha and William) – I have ordered Dr Kauffman’s book and eagerly await its arrival.
        Re: aspirin’s affect on Vitamin C – there was a paper published in 1973 by Loh, Watters and Wilson but I’m unable to access the full paper (PubMed). Also on PubMed a paper from 1982 called Vitamin C – aspirin interactions showed that the action of Vit C was blocked by aspirin when taken simultaneously (although the aspirin doses were high at 900mg) in human studies.

      3. William Bowles

        Re aspirin versus Vit C: 900mg of aspirin!!!!!!!!! I take 35mg a day, no wonder the aspirin does what it does. What else does 900mg do I wonder? How can one compare these two situations? Well you can’t can you!

  49. Randall

    Statins move over. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. https://www.ncbi.nlm…pubmed/15158307

    1. Martin Thomason

      Thank you Dr Sjoberg – that’s motivational for me to see you’re fighting the fight 18 years after your MI.
      Instinctively I’ve felt sure I needed to get off these med’s after losing a lot of bodyweight, transforming what I eat and walking everywhere instead of using the car (averaging about 120 miles per month on foot nowadays) – they feel more of a hindrance than a benefit.

      Also I’ve read the Dr Saul transcript you posted – what a powerful argument against Big Pharma


  50. Charles Gale

    F.A.O. Martin Thompson

    Hi Martin – read your aftercare medication situation with familiarity to my situation last year…almost the same observations.

    Just doesn’t add up, does it?

    Officially, I’m down from 6 meds to 5 meds (Clopidogrel no longer needed) and don’t take statins. That leaves 4 and I’m experimenting with a rotation system of dropping one and using a pill cutter to halve the dosages.

    Don’t know if you have run all this (and polypharmacy) by your cardiologist like I did last year…she wasted no time in putting the fear of God in me by stating this was all that’s keeping me alive.

    Well, I’m not scared anymore and don’t think I care too much either.

    1. Gary Ogden

      Charles Gale: See my comment about aspirin in secondary prevention. It appears to have value only as a one-month course immediately after the CV event.

      1. William Bowles

        Charles Gale: See my comment about aspirin in secondary prevention. It appears to have value only as a one-month course immediately after the CV event.

        So why does my GP insist that I keep taking the damn stuff (plus the Ranitidine) five years after my heart attack?

      2. Gary Ogden

        William Bowles: He likely doesn’t know what the aspirin research actually shows, which is that it has virtually no value in primary prevention, and some value for a short period of use in secondary prevention. Trials using buffered (with magnesium) aspirin show the best results, so were it me, I would just up my magnesium intake (which I do), and leave the aspirin on the shelf. Unfortunately, physicians too often continue to do what they’ve always done, regardless of new knowledge from research.

      3. William Bowles

        Trials using buffered (with magnesium) aspirin show the best results, so were it me, I would just up my magnesium intake (which I do), and leave the aspirin on the shelf. Unfortunately, physicians too often continue to do what they’ve always done, regardless of new knowledge from research.

        Thanks for this but there all kinds of magnesium, some appear to be better than others. Advise please…

      4. Bill In Oz

        William do not take Magnesium oxide. It is cheap & readily available but it is useless. It is poorly absorbed and will just give you diahrohea. I take Magnesium citrate. The powder form is a lot cheaper than the capsules. I just add it to some water and drink it.

      5. Gary Ogden

        William Bowles: I use three strategies for Mg. 1. A spray-on magnesium chloride brine; expensive, but lasts a long time, many months. 2. I drink Gerolsteiner mineral water, which has 100mg/L. 3. I eat lots of Mg-rich foods. Nuts have the most, but also mushrooms, spinach, beet greens, and some seafood. Mostly I prefer food sources for nutrients to supplements, partly because they taste good, but also they no doubt have co-factors that are important and of which we may not even be aware. Another consideration is that, at least in the U.S, most supplement ingredients are sourced from China, and I don’t trust food or medicinal products manufactured in China (there is much to like and esteem about this ancient land and her people, but oversight is weak).

      6. William Bowles

        Re Magnesium:
        I’m overwhelmed with options! But thanks, I’ve opted for magnesium glycinate but how does one test one against the other? I’ve also ordered some magnesium citrate. It’s all a bit, how do you prove a negative, kinda thing?

      7. Gary Ogden

        William Bowles: You’re on the right track. Bill in Oz recommends the citrate, but the other one is probably good, too. One fun way I get Mg is chocolate. My local manufacturer/supplier makes 100%, and my daily dose of 15g has about 50mg.

      8. Gary Ogden

        William Bowles: Also, Dr. Carolyn Dean is an excellent resource for understanding Mg. She has a web site, and a book, “Magnesium Miracle.”

      9. Bill In Oz

        William it could be that inadvertently the doctor has done you a favor. Aspirin is noted for lowering the risk of cancer, especially bowel cancer. It is also a popular anti-aging over the counter drug. I took aspirin myself for years for this reason. But was forced to reassess taking it after I became quite anemic in 2016. It can lead to gastrointestinal bleeding and this happened to me. I stopped the aspirin and the occult bleeding stopped..

      10. Philip Thackray

        William Bowles, Bill in Oz
        My recent search for best bio-available magnesium yielded magnesium bisglycinate available from Viva Naturals. The full chemical name is magnesium bisglycinate chelate.

        Renfrew, PA

      11. Bill In Oz

        Phil, the issue is what bioavailable magnesium is available at a reasonable price.

        Here in Australia it is Magnesium citrate from Blackmores. It is even sold in supermarkets : 100 grams of Magnesium Citrate powder for around $20.00 Australian. I tale a quarter of a teaspoon a day in water and it lasts months. And it is not mixed up with other stuff that I do not want to buy.

    2. Martin Thomason

      Hi Charles,

      No – doesn’t stack up for me. Ironically, I’d been for the mid-life Men’s M.O.T check up at my GP’s only a couple of months before my MI and was given a clean bill of health (albeit with the advice “lose a bit of weight”)!

      I too have experimented with dropping one med at a time as I was getting an aching in my chest from time to time on the full med’s and in the first few months, panicked and went along to the hospital to be checked out – but each time they could find nothing amiss and troponin levels didn’t show anything had happened to the heart muscle. I was effecively told that “it was all in my head” which caused me to stop and think. Perhaps they were right, I really don’t know. I still suffer with it from time to time.


      1. William Bowles

        I too have experimented with dropping one med at a time as I was getting an aching in my chest from time to time on the full med’s and in the first few months, panicked and went along to the hospital to be checked out – but each time they could find nothing amiss and troponin levels didn’t show anything had happened to the heart muscle.

        Ditto for me! Four times I’ve freaked out over chest pains and ended up in A&E but everything looked fine. In part this is due to the kinds of interactions I’ve had with the medical industry eg, when I asked the consultant who (allegedly) oversaw my treatment following my MI, what were the odds of having another one, he replied ’50/50′. No time scale of course. Then later, when I stopped taking statins, another consultant I was sent to see, told me that ‘after five years, stents block up’. I was coming up to five years at the time. It’s these kinds of insensitive interactions that create was is effectively, hypochondria (which I’m now trying to get treated for, well I suppose it’s all grist for the mill). It’s like you’re on an assembly line. How do these characters become ‘healers’? Eventually, my GP apologised to me for the ‘over diagnosis’.

  51. chris c

    This guy is hilarious

    I suspect that his real-life equivalents, on hearing of this paper/research, will have rapidly put out a press embargo while they decide what to do next (did I also spot some hasty Damage Control further up the thread?)

    1) an absolute ban on prescribing Viagra to heart patients (pretty much already in place)

    2) repurposing Viagra (cheap but may adversely affect statin sales)

    3) bringing out a molecular variant which can be patented specifically for CVD

    4) rapid research into a Viagra/statin combination pill which could be patented and avoids kicking a huge hole in the Cholesterol Theory (cheap but may adversely affect PCSK9 sales)

    5) rapid research into an injectable Viagra equivalent which could be added to a PCSK9 injection (most profitable but most expensive). Rumours that the marketing phrase “The One Prick Solution” has been trademarked may be premature. This might overcome the so far seriously lacking effects of PCSK9s alone.

  52. Martin Back

    I was at a funeral today of a lady in her late eighties. Many of her big family were there, down to great-grandchildren, and it was interesting to note that each generation was a little taller than the one before. You can put this down to better nutrition in childhood, and also better nutrition for the mother. I would guess that, other factors being equal, a better start in life would lead to a longer and healthier life. Is this ever controlled for in observational studies based on populations?

  53. Mark Johnson

    A person in their 80s now would have been born in the 1930s of parents who themselves would have been youngsters during WWI . I was thinking of the epigenetic consequences of food / nutrient deficits during and post the two World War years. But equally, food was likely more nutrient dense with soils likely higher in various minerals. But does height = better health anyway? Could there be an artificial element in taller, recent generations as a result of increased use of hormones in the food chain?

    1. Sylvia

      Surely we can’t keep getting taller or we would all be giants now. My husband is 6ft tall, I am 5 ft tall, our three children are in between, not as tall as my husband but thank goodness taller than me. Apparently I will be as big as a garden gnome with shrinkage!

      1. Gaetan

        But truly we have no idea. For example, my uncle is 6ft tall, my aunt is 5’9” tall and their son (my cousin) is 6’9″ tall. Literally a giant lol. When he was 18 he was 6’6″ and kept growing up. We all have no idea why he is that tall. He is in good health too.

        Garden gnome was funny, it’s good that you can laugh and do not take yourself too seriously!

  54. Bill In Oz

    Dennis Mangan has just out up a very interesting podcast interview with Dr Leo Zacharski about blood iron ferritin levels and diabetes.

    Dr Zacharski states that high iron levels damage the pancreas beta cells that produce insulin. The result is reduced capacity to produce insulin and thus reduced capacity of cells to take in sugar molecules. Thus the blood becomes chronically high in sugar, damaging various body organs including the arteries and the endothellium of arteries.

    It is a long interview. 1 hour 24 minutes. But it is worthwhile.. And suggest that optimum blood ferritin levels is around 80 for men.


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