What causes heart disease part XXI

Now, when I say that CVD is complicated, I suppose I mean it. Here is a slide that I have been pondering for a couple of weeks. It comes from a paper called ‘DDAH Says NO to ADMA.’1 And that gets my official ‘acronym title of the year award’. Something that I do not hand out lightly. Here is the key diagram from the paper.

hdp21

Actually, it is not that complicated, because it is explained thus. ‘The role of DDAH1 in the metabolism of the NOS antagonists ADMA and MMA. DMA indicates dimethylamine; PRMTs, protein arginine methyltransferases; SAM, S-adenosyl-L-methionine; SAH, S-adenosyl-L-homocysteine; SDMA, symmetrical dimethylarginine.’ That should have cleared everything up, I hope.

Joking aside. For those paying attention, and I must admit you will have to have a pretty good memory here, I did mention some time ago that PPIs increased the risk of CVD. PPIs are proton pump inhibitors such as omeprazole, lansoprazole, esomeprazole, pantoprazole and suchlike. If you take medicine to prevent stomach ulcers, or gastric reflux, and it ends in ‘zole’ it is a PPI. [Which, if you live in the UK, is not payment protection insurance, which banks mis-sold and are now paying billions in compensation].

The reason why I was pondering DDAH and AMDA is that, very recently, I was sent a paper which had the following results:

‘In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09–1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07–3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.2

Now, I already knew that PPIs increased the risk of CVD, but the risk seemed relatively small. However, the problem appears to be far worse that I thought. A two fold risk of dying of cardiovascular disease is worrying. Especially as these drugs are prescribed to millions of, mainly, elderly patients. Where the risk of CVD is already high.

For example. In England, in 2014, there were fifty three million prescriptions written for PPIs. This equates to around four million people taking PPIs every year. Almost all of them on long term treatment [The way the figures are presented makes it difficult to establish how many people actually take PPIs. Many prescriptions are written monthly, but not all. So I divided fifty three by twelve and rounded up a bit, then took a few again, because some prescriptions are two monthly – and not everyone takes them long term]

I figured that the number of people taking PPIs in the US is probably six times this, as the US has six times the population of England. [In fact, the number of PPI prescriptions per year in the US is 329 million/year – which is exactly six times that in England]. So we are talking around twenty million people in the US taking PPIs, usually long-term.

Run the figures a bit further, and the true scale of the problem emerges. Most people taking PPI are elderly, where the risk of death from CVD is pretty high, but I am going to use the average UK death rate of 150/100,000 per year from CVD [men and women combined]. So my figures are likely going to be a considerable underestimate.

Anyway, we now have a simple equation

PPIs appear to double the risk of death from cardiovascular disease. Thus increasing the CVD death rate from 150 to 300 per 100,000 per year (an increase of 150 per 100,00/year)

  • There are roughly four million people in the UK taking PPIs.
  • Four million divided by 100,000 = 40
  • Number of extra people in UK dying due to PPIs = 40 x 150 = 6,000 per year
  • Number of extra people in US dying to to PPIs = 240 x 150 = 36,000 per year
  • Number of extra people in US and UK dying due to PPIs = 42,000 per year

Which, for those of you who like such things, is the population of Grantham, the 244th largest town in the UK. Even if you don’t like such things, 42,000 excess deaths a year (rest of the world excluded) seems a big enough figure to do something about. My prediction – nothing at all will happen. When you have a problem as big and scary as this, nothing ever does.

Leaving this issue aside I was interested to find out, why do PPIs have this effect? Well, it is well known that they lower magnesium levels and sodium levels, which is not a good thing. They also seriously inhibit vitamin B12 absorption – leading to Vit B12 deficiency in many.

In my medical role, I have seen around twenty patients with such severe low sodium (hyponatraemia) due to PPIs, that they were diagnosed with delirium and required hospital admission. Which means that I have become increasingly wary of PPIs, and try to prescribe alternatives wherever possible.

That though, is an aside, as the adverse effects I mentioned do not increase CVD risk. So the question remains. How, exactly, do PPIs cause such a significant increase in CVD death? They do not raise blood pressure or blood cholesterol – or affect any of the traditional/mainstream risk factors for CVD

They do, however, have an effect on platelet aggregation. By which I mean thaty make platelets more likely to stick together – and thus start blood clotting. But this does not seem to the main mechanism at work here [although it does fit very nicely within the hypothesis that CVD is due to blood clotting abnormalities]. To quote the paper that found the increase in CVD risk with PPIs again:

‘Our observation that PPI usage is associated with harm in the general population—including the young and those taking no antiplatelet agent—suggests that PPIs may promote risk via an unknown mechanism that does not directly involve platelet aggregation.’2

If not platelet aggregation, then what? As it turns out, the mechanism by which they increase the risk of CVD is intriguing, and it all comes down to Nitric Oxide (NO). My favorite molecule. The explanation from the paper is, as follows. Again, there is much jargon here:

An alternative explanation is that the observed risk of PPIs is due to some unknown mechanistic pathway and that this pathway may not be restricted to vasculopathic patients (patients at high CVD risk – my words). In this regard, we recently reported that PPIs inhibit the enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH), which is responsible for 80% of the clearance of asymmetricdimethylarginine (ADMA)—an endogenous molecule known to inhibit the enzymaticactivity of nitric oxide synthase (NOS). An impairment in endothelial NOS (eNOS) is wellknown to increase vascular resistance, and promote inflammation and thrombosis. ADMA is a potent disease marker and independent predictor of MACE in prior observational studies. Our recent pre-clinical studies found that PPIs increase ADMA levels in human endothelial cells and in mice by about 20–30%.’

To rearrange this jargon as simply as I am able.

  • Asymmetricdimethylarginine (ADMA) inhibits nitric oxide synthase (NOS). NOS is the enzyme that converts L-arginine to l-citrulline + nitric oxide (NO). [Basically, it makes NO]
  • This means that the more AMDA you have, the less nitric oxide (NO) you can produce – especially in endothelial cells [A bad thing]
  • Dimethylarginine dimethylaminohydrolase (DDAH) is the enzyme which clears ADMA from endothelial cells (and everywhere else), by breaking it down to methylamines and citrulline
  • PPIs inhibit the enzymatic activty of DDAH, which means that you will end up with higher levels of AMDA floating about
  • With more ADMA in endothelial cells, you will have less NO
  • With less NO you are more likely to die from CVD

Now, I hope, the paper entitled ‘DDAH Says NO to ADMA’ makes perfect sense. Anagrams ‘R’ us.

In truth, I do love this stuff, when the underlying process is made clear. Perhaps that makes me Mr Supergeek 2016, but I don’t care. When I see a paper with the heading DDAH says NO to ADMA I know I am going to enjoy it. It brings together a number of strands that, when you know what you are looking for, all make sense. It reconfirms my belief that if you are going to understand a disease, you absolutely must – and I mean absolutely must – try to understand the underlying process. Or else you are just floundering about.

Once you have done this, if your underlying hypothesis is correct, then everything should fit together effortlessly. As readers of this blog know, I believe that CVD is primarily due to

  • Endothelial damage
  • Abnormal clot formation
  • Damaged clot repair systems

Which means that, when someone sends me a paper highlighting the fact that PPIs double the risk of cardiovascular death I immediately think. Does this fit into the processes above, or is it a contradiction? I hope that I can share some of the pleasure it gives me when a perfect confirmatory process emerges.

As it turns out, PPIs inhibit NO production, through a biochemical system that is well known, and has been clearly established. NO is probably the vital molecule in heart health. It protects the endothelium, it prevents blood clots, it stimulates the production of endothelial progenitor cells. Therefore, anything that damages NO synthesis will – inevitably – increase the risk of CVD.

I like to think, at moments such as this, that I get to feel a little of how Mozart must have felt whilst composing, or Einstein whilst thinking, or Michelangelo whilst sculpting. A moment of utter perfection. Order from chaos. Bliss.

Of course, I am also aware that many people will still be thinking ‘OK, this is all very well, and all very theoretical, but how do I avoid a heart attack. Give me the damned information.’

Ladies and gentlemen, I like to think that I am giving you the information. If not in exactly the form that everyone wants it. However, I promise that I shall try to lay it all out shortly – as well as I am able.

However, I can give you no absolutes. I can only help you change the odds in your favour. I do not have perfect knowledge, even if I did, the human body is still too complex (and maybe always will be) to state that ‘If you do this you cannot have a stroke, or heart attack.’

After all, whist it is an incontrovertible fact that smoking causes lung cancer, yet you can smoke all you like and never get lung cancer. On the other hand, you can never smoke, and still get lung cancer. I am equally certain that you can do everything possible to avoid CVD and still die of a stroke or heart attack. Equally, you can do everything wrong and stay CVD event free. The Gods do like to play dice with us feeble humans.

 

References:
1: http://atvb.ahajournals.org/content/31/7/1462.full
2: Shah NH, LePendu P, Bauer-Mehren A, Ghebremariam YT, Iyer SV, Marcus J, et al. (2015) ‘Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.’ PLoSONE 10(6): e0124653. doi:10.1371/journal.pone.0124653

204 thoughts on “What causes heart disease part XXI

    1. barbrovsky

      I thought this article might be of interest here:

      https://thereturnofthepublic.wordpress.com/2016/09/19/big-food-and-the-politics-of-diabesity/

      Big Food and the Politics of Diabesity
      by Dan Hind

      “What did they live on?” said Alice, who always took a great interest in questions of eating and drinking. “They lived on treacle,” said the Dormouse, after thinking a minute or two.

      “They couldn’t have done that, you know,” Alice gently remarked; “they’d have been ill.”

      “So they were,” said the Dormouse, “very ill.”

      Lewis Carroll, Alice in Wonderland

      1. The Word of the Day is Diabesity

      The UK is in the midst of a public health crisis. According to the NHS’ most recent Health Survey for England 24% of men and 27% of women are obese; 41 percent of men and 31 percent of women are overweight. Obesity has increased markedly over the last twenty years. In 1996 only about 15 percent of the population was classified as obese. The change over fifty years is even more alarming. In the 1960s obesity rates were at 1 and 2 percent for men and women respectively. Since then they have increased by 1150%.

      Reply
    2. Eugène Bindels

      Does anyone have information regarding the use and effectivenes of beta blockers and or ace inhibitors post cabg (bypass operation)

      Reply
    3. clare mcginley

      On PPIs and reflux treatments have you read norm robillard’s Fast tract diet stuf? He postulates that High Carb (specifically ‘fermentable’ carbs) diets are the cause of reflux and lots of other things it is gaining some traction (!) i think.

      Reply
      1. JanB

        Back in the bad old days, before I stopped eating bread, cereal, pasta, rice, sweet stuff in an effort to get my BG under proper control, I had a lot of ‘heartburn,’ a constantly rumbling belly and was somewhat, ahem, jet-propelled. Within a few days of dropping the carbs? Perfect peace. That was over three years ago. I think PPIs are rubbish and yet another upsetter of the body’s natural resources. Sadly though, it seems I can’t do without my daily dose of Gliclacide which my diabetic nurse has stopped because she says that at 5.8% my HbA1c is too low. Too low?????? I need a bit of advice and some TLC from all you lovely bloggers out there.

  1. Jean Humphreys

    Thanks to my favourite geek!
    I had to throw out PPI’s – I was told I needed them to protect my stomach from excess acid. I didn’t have excess acid, naughty me. I found that the cure for indigestion was to eat something pickled, a couple of times a week. I needed acid top-up.
    Thank goodness my present GP is trained – and the practice is a training one. I gather I am used as a training aid at times.

    Reply
    1. anglosvizzera

      Another ‘old wives’ trick is to take apple cider vinegar. Same result as eating pickles I guess. It certainly works for me on the very odd occasion that I get heartburn! I drink Kombucha, home-made until it’s almost like vinegar, which probably is a preventative in my case.

      Reply
      1. BobM

        One tablespoon of apple cider vinegar, taken on an empty stomach, leads to about a 10 point (mg/dL) decrease in blood sugar for me. Another benefit, though I prefer my AC vinegar with some red wine vinegar and olive oil on a salad! This lessens the acidic shock of the vinegar, and I “drink” the vinegar/oil left after eating the salad — which in a restaurant looks admittedly strange.

      2. Jennifer.

        Anglosvizzera….I am delighted to read this from you. I have now returned to drinking diluted cider vinegar…believing in its suggested glucose lowering effects. I have been making wonderful kefir all summer, and finally managed to perfect crunchy fermented veggies, which I find more palatable than pickles. I make my own yogurt, and fabulous 24 hour developed authentic sourdough. I am back to eating small amounts of fruit, and use cinnamon to moderate its glucose/ fructose content.
        (My next goal is to make Kombucha, but I need to read up on it, as I am fearful of the sugar needed in the process.)
        Result…..still off all my meds after 3.5 years….no abnormal glucose, no high b/p, no nasty indigestion, sustained optimum weight after initial 2 stones weight loss, ( which resulted in a loss of 8 inches from my waist measurement). Oh, and off 40 mg Simvastatin, never to have it pass my threshold ever, ever again.
        I acknowledge there is a place in medicine for drugs….but not the buckets full I was being prescribed, which included regular Gaviscon.
        Do I sound smug? I think I may do, but oh, if only I could get folks to realise the benefits of good nutrition and a better understanding of pharmaceuticals. I feel inadequate in passing on my recent-found knowledge, so I use Dr K’s marvellous blog to encourage anyone interested. There are fantastic, academic links on this blog, but I hope my practical applications will show what is possible.

    2. Hatty

      I had the same issue: PPIs for reflux when the problem was lack of acid. Now, even after several years off them I have biliary dyskinesia triggered by them…and solved through daily apple cider vinegar

      Reply
  2. barbrovsky

    Hmmm… I have been taking the dreaded Omeprazole until about a six weeks ago after 4 yrs on it, but it played havoc with my digestion. The fact that it could have a role in heart disease is just another nail in the coffin of another of these ‘wonder drugs’. I’m back on Ranitidine but it makes constipated!

    Reply
    1. Stephen Rhodes

      Constipated? Try upping your vitamin C intake and magnesium sulphate (Milk of Magnesia) both are important in your diet and both are probably deficient in it too – also quite difficult to take too much of either.

      Reply
      1. barbrovsky

        I started taking ascorbate 2gms twice a day a few weeks ago, before I started on the Ranitidine last week. And a banana. I was taking l-arginine but I think the Omeprazole was cancelling it out! I take beetroot extract twice a day and top up my vitc/k2 and b12, every other day. I think this is more enough pills for one lifetime. Plus I have a pretty good, balanced diet and exercise 4-5 days a week. I don’t think I can do any more.

  3. Maureen Berry

    Dr Kendrick, all you have to do to get your patients off PPIs is to tell them to adopt the Atkins diet! It works like a charm, within days. I first read about it in ‘New Atkins for. new You’ was convinced by the health arguments and after a week on it noted that the ‘extra’ reflux / pain I suffered, despite the daily Omeprazole, disappeared. After a couple of weeks I dropped the Omeprazole and I have never had reflux since (approaching 6 years).
    This is widely reported in all the discussions relating to LCHF – it is the norm. I have tried telling my doctor (not just about this but also the stellar reduction in my BP, now off all medications) but he doesn’t want to know.
    The medical profession needs to look around – prescribe your patients ‘the Real Meal Revolution’ book instead of a different drug. It’s about the most accessible read at the moment, with lovely images and good recipes for delicious and satisfying food. The weight loss is just an aside!

    Reply
    1. Jackie

      I totally agree with you Maureen. Lots of good evidence on low carb being healthy for us. Of course, this supports my posts on gluten being bad for humans. When you go low carb, you naturally go very low or even zero gluten 🙂

      Reply
    2. anglosvizzera

      Years ago, I found that even just cutting out bread helped with heartburn and now I’m eating a ‘paleo-style’ diet, I haven’t had any problems with it at all. I was rather concerned to find out that wheat is routinely sprayed with Roundup just before harvest (as a dessicant) so I’m not surprised that so many people have digestive issues when eating wheat products. Scary!

      Reply
      1. Jennifer.

        Anglosvizzera. Further to my previous response to you, I might add that I use organic, natural foods as often as I can obtain them, and ingest a good amount of high quality, natural fats. After going very low carb for about 2 years,( being type 2 diabetic and on the verge of using insulin), I am now able to accommodate nutrient-dense carbs, including wheat. I have worked out that the methods of food production and preparation are very important on the way our bodies cope with carbs, fats and proteins. I do not use any supplements….just healthy, natural foods; and, as those who have read my previous contributions…..I enjoy a daily tipple!

    3. Hithaeglir

      Yes – LCHF worked for me too. Before LCHF diet, I used to carry antacids around and had to use them every few days. Since LCHF 7 years ago, I can count the number of times I have needed these on one hand…

      Reply
    4. mikecawdery

      There is an excellent book:
      Feinman, Richard David. The World Turned Upside Down: The Second Low-Carbohydrate Revolution . NMS Press-Duck-in-a-Boat LLC.
      Dr Feinman is a biochemist who teaches med students basic nutrition. He provides a lot of detail including the metabolic pathways. In short it blows the current “advice” out of the water in favour of low carb diets for diabetes (a contributing factor in CHD)

      Reply
      1. Gary Ogden

        mikecawdery: Yes, it’s a great read! I ordered it from his website, and he sent with it a KETONE BODIES. FOOD OF OUR ANCESTORS t-shirt as a bonus. I particularly appreciated the section about thermodynamics and metabolic advantage. Somewhat subtle, but a calorie is not a calorie.

      2. mikecawdery

        Gary,

        Lucky you,
        My favourite is the ADA (American Diabetic Association quote):
        “Sucrose-containing foods can be substituted for other carbohydrates in the meal plan or, if added to the meal plan, covered with insulin or other glucose-lowering medications.”

        How close can one get to saying carbs cause hyperglyceamia without actually saying it?
        The implication is that it is OK to eat carbs because the consequent hyperglycaemia can be controlled with drugs. The ultimate answer of a snake oil drug flogger!

      3. Gary Ogden

        mikecawdery: Yes, like all the rest of the disease-charity-industry, the ADA are shills for pharma. Have you seen the Dr. Feinman interview with Ivor Cummins? They discuss some very promising cancer therapies with a ketogenic diet, sometimes with low doses of conventional treatment, and sometimes by itself. It’s on the Fat Emperor website.

  4. JanB

    Dear Mr Super Geek – thank you for this. It great the way it’s all beginning to slot together even for a scientific numpty like me. Looking forward to the book for surely that MUST be the end products of all your hard work.
    Ta ever so.

    Reply
  5. David Bailey

    At a practical level, it sounds like avoiding PPI’s would be a good plan, and would be of far more benefit than the minute (imaginary?) value of taking statins! Also, as I discovered, it is easy to get hooked on these drugs. Questions:

    1) How long do you think it takes for the risk level to drop to normal once you stop taking these drugs?

    2) What is the best alternative – Gaviscon, or an H2 blocker. When I was coping with being hooked on omeprazole, I chose Gaviscon because the description of its action sounds completely mechanical – it forms a sort of barrier that keeps the stomach contents in place.

    3) (This is probably a silly question) Can you get too much NO?

    Reply
    1. barbrovsky

      Re Gaviscon: I asked my GP whether I should use Gaviscon or Ranitidine as a replacement for Omeprazole. Gaviscon is really aimed at indigestion/acid reflux and not reducing the amount of acid in the stomach associated with taking Aspirin. Like you say, it’s a mechanical ‘solution’. BTW, Ranitidine only stays in the stomach for about three hours, so if you are taking Aspirin, make sure you take the Ranitidine first and the Aspirin within 3 hours.

      Reply
    2. Jean Humphreys

      One thing about Gaviscon – sure it forms a mechanical barrier to prevent reflux. Just be sure to remain vertical. I was given Gaviscon for indigestion while lying flat after a failed angioplasty. It worked by forcing my stomach contents upwards. Simple application of the effects of gravity.

      Reply
      1. kelly trosper

        Chris Kresser has a 6 part series on GERD. Good for those who want to treat it without destroying your CV system 🙂

        Thanks Dr. K. excellent stuff.

    3. JanB

      Do try low carb. After two or three days my miserable stomach was all cleared up – no heartburn, no burping and no being jet propelled, if you get my meaning and its been like that ever since. At least 3 years

      Reply
    4. David Bailey

      I must say, I found Gaviscon reasonably effective to let me come off omeprazole. Since I took it after food, I wasn’t horizontal.

      One other feature of omeprazole (and presumably other PPI’s) is that they aren’t really titrated – I mean I went from having high stomach acidity taking just diclofenac, to having very low stomach acidity while taking diclofenac and omeprazole – sufficiently low to stop me absorbing B12. If people could take lower doses (OK you could break open the capsules) and slowly ramp the dose up until they stopped getting acid reflux, they would probably end up taking a much smaller dose.

      Reply
    5. Steve H

      For what it’s worth, I used to suffer from regular acid reflux at night and always had a packet of Rennies to hand. Fifteen years ago I was diagnosed with sleep apnea and started to use a CPAP machine every night. Since then I have been reflux free.

      Reply
  6. Jackie Kay

    This fits in with my earlier response I sent which showed the link with gluten and heart disease. Gluten intolerance/coeliac disease patients often have GERD, so likely prescribed PPI’s.

    https://www.glutenfreesociety.org/acid-reflux-linked-to-gluten-intolerance/

    A recent research study linked peptic disease (heartburn, GERD, stomach ulcer) to gluten exposure in patients with gluten sensitivity. PD (peptic disease) is not uncommon in the presentation of CD (celiac disease). It is more likely to be found in the second decade of life.

    Reply
    1. anglosvizzera

      As I put above, sometimes the problem is too little stomach acid (probably more than ‘sometimes’) and these levels get less as we age.

      Additionally, modern wheat is a different beast from what we ate a few decades ago and many people have problems with not only gluten but other proteins that are in wheat. Furthermore, wheat is sprayed with Roundup (yes, even in the UK) before harvest to dessicate it ready for harvest – that cannot be good for our stomachs! “Wheat Belly” is a good read, regarding intolerance. Obviously gluten is in other foods too, but I’ve found (as a complementary practitioner) that most people associate their digestive problems with wheat products.

      Reply
      1. Jackie

        Anglosvizzera, I too was a complementary practitioner though now retired. Thank you for adding this information to back up my comments. After 30+ years of research into gluten, I’m so pleased to see so many Drs doing research and saying how bad grains are for us humans. Usually, they’ve had their own illness to overcome and dug deep to find out. It was the same with me. If anyone is interested further, then google or look on youtube for Dr Tom O’Brien, Dr Peter Osborne, Dr Rodney Ford to name a few.

        There are over 200 conditions linked to gluten sensitivity in the medical literature. The connection between these and gluten is well established.

        http://www.greenmedinfo.com/blog/200-clinically-confirmed-reasons-not-eat-wheat

        Grain Brain, Wheat Belly, No Grain, No Pain. These are just a few of the books I’d recommend everyone read.

  7. Millie Thornton

    Excellent. My type of biochemistry too. It’s lovely the way it all fits together. I totally agree that it’s important to look at the science behind the disease – pity not all doctors do that.

    My husband was prescribed Lansoprozole and told he’d have to take it for the rest if his life. A second consultant said that he only needed to take it when necessary (usually after New Zealand Sauvignon Blanc…) so that’s what he does but I’d like him to stop taking it. I’m working on that.

    I’ve never been to Grantham but being Scottish I discovered it’s the equivalent of a population of that between Glenrothes and Greenock – interestingly they all begin with G. Whatever or wherever, as you say, it’s not great.

    Reply
  8. Mrs Sarah Chard

    Just one thought… as PPIs have been around a while, is it possible that the increased deaths due them are already impacting the death rates – so maybe not prescribing them could actually bring down the 150/100,000?

    This one’s a bit technical for me, I’m just going to keep eating real food!

    Reply
      1. Håkan

        I ask because you wrote “They do not raise blood pressure or blood cholesterol”. What is the source for this statement?

      2. Gert van der Hoek

        “Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats”

        “Our results suggest that part of the hypotensive effects of oral sodium nitrite may be due to its conversion to NO in the acidified environment of the stomach. The increase in gastric pH induced by treatment with omeprazole blunts part of the beneficial cardiovascular effects of dietary nitrate and nitrite”.

        Full article: http://www.sciencedirect.com/science/article/pii/S089158491200336X

      3. David Bailey

        I am very curious about how NO works in the body, because NO reacts spontaneously with oxygen to produce NO2, So can it actually be transported in the blood, or does it have to be synthesised on site?

    1. Alan Tillotson

      Brilliant as always, but one slight problem – you can save 42,000 people from death, but at a cost of 4 million people mucking about with upset tummies.

      You may want to mention that there are many simple ways to overcome acid refux that don’t rain your odds of death – DGL licorice, drinking more water, dietary changes, microbiome issues, esophageal valve repair using specific nutrients etc.

      Reply
      1. anglosvizzera

        Even ingesting more ‘acid’ like apple cider vinegar. Seems a bit of an oxymoron but many people are now thinking the problem is due to too little stomach acid (eg Dr Chris Kresser)

      2. ellifeld

        Anna Bunton, DGL is deglycerized licorice, which is licorice without glycyrrhizin, a chemical found in licorice. There is some evidence that the glycyrrhizin raises blood pressure.

    2. Leon

      Maybe in some people, certainly not in all. My husband was much too long on PPI’s but had a very good blood pressure (about 80/120) both before and during PPI therapy. As PPI’s make the uptake of several nutrients difficult, there might be processes other than NO synthesis at work. Maybe deficiencies that interfere with the clotting systems.

      Reply
  9. Gordon Ferris

    Great analysis Sherlock! My Omeprazole tablets are now in the bin. Funnily enough (or rather, Not) I was put on these PPIs last year to counter my heartburn. Great stuff I thought. But in April this year I had a stroke with no known health problems. Coincidence?

    Reply
    1. barbrovsky

      Well I’m not sure if this was just my reaction to stopping Omeprazole but I had all kinds of withdrawal symptoms and my GP advised that I taper off the damn thing, which I did by reducing over time (a couple of weeks) my intake of the stuff (I also stopped taking the Aspirin during the period).

      Reply
  10. Jackie Kay

    Looking at the comments, it’s no surprise to me (34 years of gluten research) that so many people are on ppi’s for acid reflux which is caused by diet, normally gluten is the culprit as many comsume it three times daily. Gluten from wheat has changed in the last 50 years with crossed crops to yield much more gluten, which is why we now have the explosion of coeliac disease and auto immune diseases. A recent study showed that NO human can digest gluten, hence the inflammation it causes inside (or outside) the gut by breaking down the gut barrier (gut permeability), inflammation can then occur anywhere in the body, so in the brain, dementia, depression, joints, (arthritis), skin, (acne, psoriasis) digestive organs, heart. This means poor absorption of vits and mins so you get fatigue, endocrine disruption (hormonal issues). The list is endless. I’ve helped so many clients get better over the years. I urge everyone to read up. Just google whatever complaint and add the word gluten.

    Here’s a link to heart disease and gluten:

    https://www.glutenfreesociety.org/heart-disease-and-gluten-sensitivity/

    “…A number of research studies have linked gluten sensitivity to different forms of heart disease. The first study below discusses gluten induced autoimmune disease of the heart. The second study discusses how malabsorption of nutrients (in this case carnitine deficiency) induces cardiomyopathy (disease of the heart muscle)…”

    Reply
    1. anglosvizzera

      Not only that, but wheat (even in the UK) is sprayed with Roundup before harvest. I’m convinced that also has an adverse effect on our digestive systems.

      Reply
      1. Frederica Huxley

        The other thing to consider is the way bread is commercially made in this country since the ’70s; specifically by the Chorleywood method, which can produce a finished loaf in an hour from mixing the dough! Accelerants, additives, colours, preservatives and sugars are added to wheat that has been grown with pesticides and dessicated before harvesting. Fungicides are necessary, as the loaves are packaged hot. I love bread; until fairly recently it was ‘the staff of life’. I make my breads with organic wheat, using a sourdough starter, and luckily to date have never experienced any digestive problems!

    2. mikecawdery

      Thank you for the link. It is becoming more apparent that gluten is a potential risk to a proportion of the population and is not just involved in coeliac disease – an extreme condition. That it can involve the heart is an interesting finding but not entirely surprising given the CHD association with obesity.

      Reply
  11. Jennie

    So Dr K yet another brilliant informative post!
    What do you do if you are prescribed a cocktail of drugs (as my 35 year daughter has been) for Idiopathic Pericarditis? She is now taking
    Omeperazole
    Prednisolone ( on a reducing level)
    Colchicine
    Methotrexate
    Folic Acid
    She has regular blood tests, and they always say, ‘your ferretin level is low’
    Surely this has to do with the Vit B12 part of your latest post.
    She is constantly saying her tummy is upset from this horrible cocktail of drugs, but surely she needs to take the Omeperazole as she is taking so many other medications.
    She has has 2 ‘flare ups’ this year already and the drugs just seem to be increasing.
    To think that this too could cause CVD is yet another worry.
    Kind Regards
    J

    Reply
    1. Jackie

      Jennie, take a look at the article I posted above: Here’s an extract:

      “Autoimmune Heart Disease

      Acute pericarditis (inflammation of the sack surrounding the heart) can be caused by virus or bacterial infection, but 85% of the cases have an unknown etiology (cause). The common presence of pro-inflammatory cytokines in the fluid around the heart and antinuclear antibodies (ANA – a blood marker commonly used to help diagnose lupus) in the serum as well as new autoimmune disease diagnosis lead the authors of this paper to suspect that peridarditis itself is caused by an autoimmune process.”

      Read more at https://www.glutenfreesociety.org/heart-disease-and-gluten-sensitivity/#9ipdBUDfYwpkHvHj.99

      Reply
      1. Jennie

        Thank you for the replies!
        We Have been researching the gluten connection for a long time and have already read the above article, and dozens more which link gluten with Pericarditis. As my brother and my niece both have celiac disease (diagnosed by small bowel biopsy) I’m pretty convinced there’s a link between gluten and my daughters 2 year illness.
        I think my daughter feels she needs to wait for a bowel biopsy before taking Gluten out of her diet completely. ( Her blood test came back negative) Her Consutant said he could arrange for her to have one but we are still waiting.
        I went Grain Free at the beginning of the year (because of the family history) and find websites like (Diet Doctor) and (Fat is My Friend ) very useful , and I don’t miss grains at all!

  12. Louise H

    Thanks for the lovely analysis. My 14 year old daughter was prescribed omeprazole by the GP for stomach pains. It gave no relief. Next occurrence I did a ‘sodium bicarb test’ on her which showed her to have low stomach acid. Drinking the juice of half a lemon in some water stopped her pain. She’s now empowered. I suffered acid reflux every night for years and took nightly antacids but when i went gluten free it stopped in 2 days. Never had it since. Neither of these solutions harm us.

    Reply
    1. Frederica Huxley

      Two other things to try – ACV instead of lemon juice, or just eating an apple! Ironic that PPIs are prescribed to dampen down stomach acid, when in reality, the problem quite often is too little stomach acid.

      Reply
    2. anglosvizzera

      More evidence to support the theory that these problems are related to too little stomach acid not too much. My youngest daughter was also given Omeprazole – she now has a craving for pickled gherkins and, as far as I know, is off the drug. Maybe her body is trying to tell her something?! Gluten is so problematic from so many aspects…good idea to ditch it!

      Reply
  13. Sylvia

    And my lovely brother in law who died soon after stents were fitted, having only weeks before his death been diagnosed with CVD. His history of TB, pancreatitis and then GERD, for which he was taking PPI medication makes him sound a poor specimen, he was not. An active happy man, my sisters good cooking, did the medication play a part in his CVD, who knows.
    I cannot tell her, as she says, she feels as if she has lost half of herself.
    It seems to me the medical profession and the pharma industry do more harm than good.
    Complimentary gentle approaches have a part to play. Dr Kendrick, thank you.

    Reply
  14. dearieme

    “A two fold risk of dying of cardiovascular disease is worrying”: really? I thought they were saying that the risk was increased by 16%. Mind you, their English is rotten so what they said is ambiguous.

    Reply
  15. Gay Corran

    Brilliant once again, Dr K! I agree with all the posts here which note that going gluten free seems to stop GERD in its tracks. I persuaded my husband, who was suffering acid reflux, to stop eating bread, and lo and behold! No reflux! Except when he eats bread in some form. No need for drugs, if going gluten free does the trick. I wish more people knew this. When we told our GP he said, disbelief in his voice: ” Well, I’ve never heard THAT before!” But then, he didn’t believe me when I told him I was having an adverse reaction to an antibiotic, and told me to complete the course. (I felt so ill I didn’t complete it.) And he keeps trying to get us both back on to statins. When I asked him about statin damage to mitochondria and the mevalonate pathway he didn’t have a clue what I was talking about.

    Reply
  16. JDPatten

    What keeps that little esophageal valve closed to prevent acid reflux?
    Acid.
    Normal valves stay tight shut in the presence of acid.
    Reduce the acidity with “zole” and the valve loosens. Reflux of weaker acid still burns!
    (Weaker acid also inhibits proper digestion; allows survival of Clostridium difficile, Helicobacter pylori, etc.)
    Solution:
    Increase acidity. Counter-intuitive seeming only if you don’t grasp the process.
    There are over-the-counter stomach acid boosters for the purpose.

    Reply
  17. Danny Evatt

    As a side-line, I have always suffered from pretty severe PVC’s. Though I was told by the medical world that they were “harmless”, they did not seem “normal” and often woke me from sleep, etc. However, since I started taking L-Arginine (and heavy doses of vitamin C), they have gone away.

    https://www.amazon.com/gp/product/B00D94CIC2/ref=oh_aui_detailpage_o00_s00?ie=UTF8&th=1

    I have often wondered what effect L-Arginine, i.e. NO has on the heart – evidently a great deal more than I suspected! Could a lack of NO (for whatever reason) also be a cause of CVD?

    Reply
      1. Uricon

        With the danger of becoming boring let’s hear it again for uric acid. UA reduces NO, there is also seemingly some relationship between UA and endothelial function. l-arginine is known to incease UA. LA is also dangerous in large supplement quantities, it is thought to bring on herpes, should it exist. L-citrulline maybe the better route to go down, you have suggested this last article but it was with LA as well. Water melon great source but you need to live in a vat of it and all that fructose. Sorry but in the verified atmosphere of this and other such blogs everything seems to be on the margin, NO, vit k, vit c, too much too little cholesterol, too much too little sat fat, carbs, it’s the insulin stupid, aged over 60 all bets are off etc. So I say look after your uric acid levels ( it’s not on your list of possible factors of cvd).

  18. Errett

    The best of the series—sailing around the Greek Isles seems to be conducive to mental health.
    NO is my favorite molecule also—

    Reply
  19. Mark Rand

    Malcolm I have speculated for a while that this is why ACE inhibitors provide RR reduction similar to statins. However nobody seems to ever want to discuss this. I say if you have mild hypertension and slightly elevated lipids (or not) an ACE inhibitor is a far better choice, ditch the statins. I would have to go dig papers out of the archive but the reduction is independent of blood pressure reduction.

    Reply
  20. mikecawdery

    Dr Kendrick,

    Once again an interesting and stimulating article relating to the causes of CHD and of an unrelated pharmaceutical increasing the risk of cardiac mortality. One is left wondering at the possibility of similar effects of other drugs.

    In the extract starting with “In multiple data sources…….” this is an example of my pet aversion a Hazard Ratio without numbers. I suspect that the true increase in risk is small.

    A difficult paper to follow in a short time but I found the following:
    Extract: there were 58 cardiovascular mortalities during a median follow-up period of 5.2 years (interquartile range, 4.1–6.3). Using a Cox proportional hazard model, an unadjusted analysis showed a 122% increased cardiovascular mortality risk among PPI users as measured by the hazard ratio (HR = 2.22; 95% CI 1.19–4.16; P = 0.013).

    This suggests to me the actual numerical increase of cardiac mortalities was in the order of say 60 extra cardiac mortalities (122% undjusted) in 5 years. The graph from the PLOS report suggests that the actual percentage difference is only 2% from CHD Fig 2 from PLOS shows a Kaplan–Meier curve representing the survival function from cardiovascular mortality for patients on PPIs versus controls. As with the text-mining analysis, no association was seen with H2Bs in either unadjusted (HR = 1.05; 95% CI 0.15–7.59; P = 0.962) or adjusted (HR = 1.00; 95% CI 0.14–7.26; P = 0.996) analyses.

    The HR rate of 2+ times is a relative risk, which is probably an inflated risk. Without the actual numbers on which this HR is based it is impossible to establish the true rate and risk. For example a recent article in the Telegraph on HRT indicated that the use of HRT drugs increased the risk of breast cancer by 2-3 times. The actual numbers were an increase from 14 per 1000 to 34 per thousand (a relative rate of 2.43 times) but actually is 20 per thousand or 2% or an unlikely probability of 0.02 for an individual.

    Yes it is significant statistically but is it relevant to the individual patient?

    Take for example your estimate of the number of extra deaths:
    “Number of extra people in UK dying due to PPIs = 40 x 150 = 6,000 per year per 100,000; this is 6%”.

    I am confused. What is the true risk to the individual patient on an annual basis or 5 year basis or whatever?

    Reply
    1. Dr. Malcolm Kendrick Post author

      Mike. My calculation is that is the risk of dying of CVD in one year (average men and women across the whole population) is 150/100,000/year. Which is a risk of 0.015% per person. If you double this risk, you are increased the risk by 0.015%. You are doing this for four million people, per year. So, the equation is, as I worked it out. 4,000,000 x 0.0015 = 6,000/year. But I made a mistake, because the risk was doubled over five years, not one. So I need to divide by 5. So the increased number of deaths is 1,200, not 6,000. I shall amend.

      Reply
      1. mikecawdery

        Dr Kendrick

        Many thanks. This ends up as a probability of 1200/4 million p.a. for the individual or a probability p = 0.0003 so that the probability of the individual NOT affected is p = 0.9997; not something I would overly worry about. But once again it demonstrates how HRs inflate the individual risk. Just like Collins “treat 3 million, save 10,000 per year” = 1 saved per 300 treated. I am seriously worried at this HR practice in medical research; as a statistical tool for demonstrating a significant difference is one thing. Scaring the hell out of patients is quite another and is certainly not “patient friendly”

        However I do take your point on the metabolic effects and their importance. Anything that reduces NO is bad. One just wonders at what other pharmaceuticals reduce NO

  21. Nissen Bron

    I don’t know if you get JAMA, but the Sept. 12th issue had an article about ( oh! Shock oh! Surprise) that for 50 years the sugar industry was paying “scientists” to downplay the role of sugar in heart disease and pointing to fat as the real culprit.

    Reply
    1. barbrovsky

      From the article:

      The internal sugar industry documents, recently discovered by a researcher at the University of California, San Francisco, and published Monday in JAMA Internal Medicine, suggest that five decades of research into the role of nutrition and heart disease, including many of today’s dietary recommendations, may have been largely shaped by the sugar industry.

      Reply
      1. Dr. Malcolm Kendrick Post author

        I know. I have been sent these papers by numerous people. Only two things to say. First, we are still too much in thrall to the ‘experts’, most of whom are paid vast sums of money by commercial organisations. Second, the issue of corruption in medical research is so big and scary that no-one dares to tackle it.

  22. Maureen H

    My respirologist offered me a prescription for a PPI when I told him about the reflux I was having. It seems to be a common complaint of people with IPF, (which I have), and other respiratory diseases. In fact there has been some hypothesizing that GERD may be a cause of IPF, because of acid leaking down the trachea into the lungs. Before I took his suggestion I looked up the effects of PPIs. And discovered that in effect it is a form of induced achlorhydria. Side effects include increased incidence of pneumonia, which I need like a hole in the head. Osteoporosis, worsening of GERD, and a host of other problems related to malabsorption of electrolyes, vit B complex and other vitamins such as C and K. So no, I won’t take them. Like others I cut out grains and within 48 hours the reflux has gone, never to return in four years. When I told my respirologist what I had done, and why, he said ‘you shouldn’t have to deprive yourself of bread and all the good things’.

    Reply
    1. John U

      I have read many responses by doctors reported by patients such as the one you received, but I have to say that this response has to be the most ridiculous. Shame on him. He should be banned from the profession.

      Reply
  23. Ernie Berry

    Dr Kendrick, it seems then we would be doubly damned, as large numbers of PPI scripts are written by GP’s simultaneously with Cox-1 and 2 inhibitors such as Naproxen for muscle and joint pains. And of course these painkillers also have a risk attached to them of CVD especially the COX-2’s; so in providing the antidote to the side effects of the pain killer the risk is likely increased further.

    Pretty soon Pharma will come up with an antidote to the side effects of the antidote you are taking for the side effects of the primary drug you have been prescribed. Oh… may be they have and I missed it.

    Reply
    1. Jackie

      Once again, we can look to the dreaded gluten (bread) for problems with muscle and joints (inflammation) pain.

      Gluten consumption causes weight gain and leads to muscle atrophy (loss) in two primary ways: Inflammation – Gluten can cause the immune system to literally attack the muscle and joints leading to chronic pain and inflammation.

      Gluten Can Cause Universal Inflammation.
      https://www.glutenfreesociety.org/eating-gluten-a-quick-way-to-muscle-pain-and-weight-gain/

      Reply
    2. barbrovsky

      Hilarious!? I took Omeprazole to counter the effects of the Aspirin but without knowing actually how much acid there was in my stomach! When I asked the ‘consultant’ about this he told me they were working on a test for it. So it’s all thumb-sucking and basically guesswork! It’s outrageous, playing Russian Roulette with our health.
      BTW, another ‘side effect’ of Omeprazole is AGGRESSION, the info in the box even warns you but who bothers to read it? Even doctors ignore them, yet it explained why I would lose my temper over pretty much nothing at all and wonder after it, why I did that?

      Reply
  24. ellifeld

    Something that has bothered me in another context regarding PPIs is the almost nonchalant prescribing for infants. I’m pretty sure it’s very common for any infant who vomits to get PPIs. I can’t believe that for millions of years infants didn’t need these and suddenly they do. Either infants have been vomiting forever or a change in their diets recently is the cause. But I’m positive PPIs aren’t the solution.

    Reply
  25. Joe

    “Read my lips. No new taxes.”

    “The check is in the mail.”

    “I’m from the government and I’m here to help you.”

    “This is going to hurt me worse than it hurts you.”

    “Let me be honest with you.”

    “Honey, that has never happened to me before.”

    “If you like your doctor, you can keep your doctor.”

    And now we have:

    “However, I promise that I shall try to lay it all out shortly – as well as I am able.”

    Sorry, Doc, sometimes I just can’t stop myself!

    Reply
    1. annielaurie98524

      The underlying theme for avoiding CVD has been “laid out” in all the articles: avoid taking prescription meds. There may be a few rare instances where one needs these for a short while for some acute problem. But for chronic issues, there are usually natural ways to address them — lifestyle changes, diet, etc. Just about all the commonly-prescribed patent drugs have horrible side effects, most of which include raising one’s risk for a major illness that can be lethal.

      Reply
  26. Susan

    Interesting. In the past 3 weeks, both of my brothers have undergone cardiac procedures: one a stent; the other a 4 vessel bypass. And both have been long term PPI users. I’ve tried to tell them for several years now that if they’d ditch the bread/carbs, they could also likely ditch the reflux and the PPI. But, like many, many others, they don’t want to “deprive themselves of the good stuff,” as noted above. Dumb.

    Reply
    1. John U

      I truly believe that the reason government agencies do not recommend the low carb diet on their web sites is precisely what you said – deprivation. It is politically dangerous to suggest to folks that they might improve their health by eating less carbs and more fat. The governments are between a rock and a hard place. Only bankruptcy might precipitate some rational behavior. However, the fact is that only a small percentage of the voting population is suffering from health problems, for now, so the issue can be delayed and passed on to the next bunch. I am not expecting to see much change in my lifetime, but I hope I am wrong.

      Reply
      1. Stephen T

        John, I think some dietitians are stuck in the mindset given to them in their initial training. Others are simply frightened of admitting such a collosal and damaging mistake. I’ve heard it said in America that the American Diabetes Association is frightened of the scale of the possible legal action if they admit that eating carbohydrates (glucose) might not be wholly wise for someone struggling to control their blood sugar.

  27. Soul

    It’s been awhile since I worked on my family genealogy, but the town Grantham sounds familiar. Most of my family, mom and dad’s side, immigrated from all over the British isles to America. For my sake I’m glad the Grantham clan left when they did. : )

    Frightening to read about a likely deadly side effect to the common PPIs. I can remember thinking that when someone young passes away it is considered tragic. When an older person passes it is expected and often little noted. With the required 6 prescription medications elderly persons are to take, it might even be noted that the person must have been in poor health taking so much medicine.

    Not really a joking matter, but little surprises me any longer in the medical field. I believe PPIs have a slight addictive quality to them also. I remember reading they are difficult to stop, as once done the reflux comes back with a vengeance for awhile. That was my father’s experience too. I believe he eventually was able to stop the PPI though.

    Interesting also about how the PPIs might work in leading to heart disease, by inhibiting NO production.

    Reply
  28. Luana

    What perfect timing for this post, thank you! My husband went off omeprazole two weeks ago after being on it for a decade. Essentially we were terrorized into the “necessity” of PPI’s for life due to Barrett’s Esophagus. The party line was that BE was strongly associated with esophageal cancer and the PPI’s were the best option for preventing a progression. Now we find out that not only is that not true (numerous studies), but it’s looking like it’s the long term PPI usage that’s associated with esophageal cancer—a complete 180!

    http://www.medscape.com/viewarticle/823403. “No cancer-protective effects from PPI’s were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia.”

    The upside in this story is that when we discussed the decision to go off omeprazole with the gastroenterologist, he said, “Well, continuing with the drug is the standard of care, but I have to say, if it were me and I was on any kind of drug, I’d do everything in my power to go off of it.” Definitely not what we expected to hear!

    So, my husband’s two weeks off the drug. We’ve been on a ketogenic diet for a year, and he’s lost 30 pounds and shrunk his large hiatal hernia, making this easier. But it is a bit of a struggle despite the low carbs. We’ll try the ginger and see if that helps. I’m wondering though about the apple vinegar when you’re transitioning off. Isn’t the issue with coming off an over-production of acid through hypertrophy of parietal cells? Would ACV exacerbate the acid problem?

    Thank you Dr. Kendrick. I’m so grateful to you for your work and for this excellent community you’ve created!

    Reply
    1. David Bailey

      When I had reflux after stopping omeprazole, as I described above, I looked for suggestions on the internet, and several people suggested ending a meal with an apple. I think by then I was beginning to get over my dependency on omeprazole, so I can’t tell you if it works.

      Reply
  29. Stumptowner

    Perhaps you will address this later, but if endothelial NO is vital to preventing CHD, then does taking Nitroglycerin pills reduce the risk of CHD in addition to relieving the symptoms of angina?

    If so, should people at high risk CHD be taking Nitroglycerin whether or not they have amgina?

    Reply
  30. Sandy

    Here’s the real kicker. Cardiologists prescribe Aspirin and Plavix to elderly patients to “prevent” CVD, then also prescribe a PPI to “protect” the gut.

    Reply
  31. John U

    Thank you Dr. Kendrick for another very interesting post. I didn’t know much about PPI’s before (don’t take any drugs) so it was a revelation to me, especially the vastness of the problem.

    I also do not suffer from GERD or any similar problem, but I do know several people who do. So it was with great interest to read all the comments above from folks who solved their Gerd problem by eliminating Gluten or going on a low carb diet, or even drinking Apple cider vinegar.

    All of these remedies actually fit with a theory expounded by Dr. Michael Eades in his blog at this link: https://proteinpower.com/drmike/2013/09/23/gerd-treat-low-high-carb-diet/
    Everyone should read this post if you have not done so before because it makes total sense. In it, Mike Eades explains how he met with a microbiologist friend and the discussion went onto the subject of Gerd. His friend suggested to Mike that the reason for the reflux is gas forming in the upper small intestine, at the exit of the stomach, due to eating of simple carbs (such as bread and sugars usually). Bread will start to break down into glucose even in the mouth due to the action of saliva. By the time the bread reaches the upper intestine, it is already transformed partially into glucose and is providing a great meal for the bacteria which are present there. This bacterial action results in gas which then has to escape and it does so through the esophagus. Hence acid reflux because the gas then entrains some stomach acid. If you stop eating simple carbs well before bedtime (of just stop eating them anytime), the problem should go away virtually instantly. Stop feeding the bacteria in the upper tract and they will die, and GERD will stop.

    Reply
  32. gazzer90Tony

    An interesting aside to long term taking PPI’s, and their effect of lowering NO, thus increasing the risk of heart problems, are the effects they can have on other periphery parts of the body. Men taking PPI’s long term often suffer from erectile dysfunction, often putting it down to age, though in many cases it is low NO levels caused by PPI’s. Whilst taking L-arginine can help, long term medication of PPI’s take time to get out of your system, and maybe by then the damage is done. L-arginine supplementation may prove to be an essential part of a ‘growing old disgracefully’ supplement!
    PDE5i inhibitors (Viagara etc) work by increasing blood flow to ‘peripheral’ parts. Like many contributors to these blogs, I am on LCHF diet, just had my 1st month free of lansaprazole, (after 12 years 15mg daily) and now using ranitidine as required, so far without problems. (Anti-aging effects of L-arginine M Z. Gad and Lifestyle medicine approach to erectile dysfunction, Dr Joseph Debe)

    Reply
  33. Nigella P

    Fantastic post – as ever. On the thyroid support website I frequent, we see so many people on PPIs, when they actually have low stomach acid. They need PPIs like a hole in the head, as often they have low B12, low magnesium and other essential vitamins & minerals for good thyroid function. I’ve posted a link to this post Dr Kendrick, I hope that is ok.

    Reply
  34. Errett

    Vitamin D deficiency changes the intestinal microbiome reducing B vitamin production in the gut. The resulting lack of pantothenic acid adversely affects the immune system, producing a “pro-inflammatory” state associated with atherosclerosis and autoimmunity.

    Gominak SC1.
    Author information
    Abstract

    STUDY OBJECTIVES:

    Vitamin D blood levels of 60-80ng/ml promote normal sleep. The present study was undertaken to explore why this beneficial effect waned after 2years as arthritic pain increased. Pantothenic acid becomes coenzyme A, a cofactor necessary for cortisol and acetylcholine production. 1950s experiments suggested a connection between pantothenic acid deficiency, autoimmune arthritis and insomnia. The B vitamins have been shown to have an intestinal bacterial source and a food source, suggesting that the normal intestinal microbiome may have always been the primary source of B vitamins. Review of the scientific literature shows that pantothenic acid does not have a natural food source, it is supplied by the normal intestinal bacteria. In order to test the hypothesis that vitamin D replacement slowly induced a secondary pantothenic acid deficiency, B100 (100mg of all B vitamins except 100mcg of B12 and biotin and 400mcg of folate) was added to vitamin D supplementation.

    METHODS:
    Vitamin D and B100 were recommended to over 1000 neurology patients. Sleep characteristics, pain levels, neurologic symptoms, and bowel complaints were recorded by the author at routine appointments.

    RESULTS:
    Three months of vitamin D plus B100 resulted in improved sleep, reduced pain and unexpected resolution of bowel symptoms. These results suggest that the combination of vitamin D plus B100 creates an intestinal environment that favors the return of the four specific species, Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria that make up the normal human microbiome.

    HYPOTHESES:
    1) Seasonal fluctuations in vitamin D levels have normally produced changes in the intestinal microbiome that promoted weight gain in winter. Years of vitamin D deficiency, however, results in a permanently altered intestinal environment that no longer favors the “healthy foursome”. 2) Humans have always had a commensal relationship with their intestinal microbiome. We supplied them vitamin D, they supplied us B vitamins. 3) The four species that make up the normal microbiome are also commensal, each excretes at least one B vitamin that the other three need but cannot make. 4) Improved sleep and more cellular repairs eventually depletes body stores of pantothenic acid, causing reduced cortisol production, increased arthritic pain and widespread “pro-inflammatory” effects on the immune system. 5) Pantothenic acid deficiency also decreases available acetylcholine, the neurotransmitter used by the parasympathetic nervous system. Unopposed, increased sympathetic tone then produces hypertension, tachycardia, atrial arrhythmias and a “hyper-adrenergic” state known to predispose to heart disease and stroke.

    Copyright © 2016 Elsevier Ltd. All rights reserved.

    KEYWORDS:
    Arthritis; Atherosclerosis; Autonomic nervous system; Hyper-adrenergic; Intestinal microbiome; Pantothenic acid; Pro-inflammatory; Sleep; Vitamin D deficiency
    PMID: 27515213 DOI: 10.1016/j.mehy.2016.07.007

    Reply
    1. Frederica Huxley

      Interesting study, especially as I keep my vitamin D in the 60-80ng/ml range. It would appear that I should add B vitamins to the vitamin K2 I already take with my D3.

      Reply
  35. mikecawdery

    Eating cheese could be good for the heart – now that is a change – dairy and fat
    http://www.standard.co.uk/lifestyle/health/eating-cheese-could-be-the-key-to-a-healthy-heart-say-scientists-a3350541.html
    http://www.ncbi.nlm.nih.gov/pubmed/?term=Am+J+Clin+Nutr.+2016+Feb%3B103(2)%3A356-65.
    CONCLUSIONS:
    In this Dutch population, higher SFA intake was not associated with higher IHD risks. The lower IHD risk observed did not depend on the substituting macronutrient but appeared to be driven mainly by the sums of butyric through capric acid, the sum of pentadecylic and margaric acid, myristic acid, and SFAs from dairy sources. Residual confounding by cholesterol-lowering therapy and trans fat or limited variation in SFA and PUFA intake may explain our findings. Analyses need to be repeated in populations with larger differences in SFA intake and different SFA food sources.

    Reply
  36. someone

    I think people who take PPI in order to protect the stomach lining from damage caused by other medications (for example, NSAID’s) could take collagen and digestive enzymes supplements. Also, vitamin c seems to be good for every tissue. Collagen (bone broth) is a good source of arginine. I wonder if antiinflamatory medications have a better effect when taken in association with collagen and ascorbate. I guess not, because if it were true then voltaren would come packed with collagen and ascorbate. Remember that pharmaceutical companies always have in their mind the optimization of their drugs effects, that is the enhacement of the beneficial effects and the reduction of the detrimental effects… NOT!

    Reply
    1. Dr. Göran Sjöberg

      someone,

      “Bone broth” – that’s it!

      It is, since millennia, well recognised that bone broth and organ “meat” is about the most healthy food you can get not least among the lapps where I am presently dwelling.

      With my LCHF-culture this is the “crown”. I have just ordered 40 kg of bones for broth and 25 kg organ from two grass fed cows and since this today is for “weird” reasons not valued I have it basically for “nothing”.

      Being now very close to the yearly mouse hunt in Lappland (I was actually invited to participate) it is a sad fact in our “modern world” to note that the most nutritional valuable parts of the animals, organs and bones, are just thrown away. I’ll see if I at least can salvage some mouse livers.

      Reply
      1. Gary Ogden

        Dr. Goran: How right you are! I have a cup of homemade broth every morning with butter and sea salt (fat aids mineral absorption; this is why Tibetans put yak butter in their tea). And small amounts of organ meat two or three times a week, always liver and heart, and sometimes sweetbreads, kidney, pancreas, testicles, or tongue, whatever I can get. Mad cow disease has unfortunate made brain unavailable, but it’s good, too, and delicious. You’re right, they throw them away. They say people won’t buy them, but during WWII our government promoted the eating of organ meats domestically so the muscle meat could be shipped to the troops (who needed the nourishment of the organs more than civilians, at least in the U. S.).

      2. Luana

        Goran,

        I’m making grassfed bone broth as I write!

        I have a question for you. I’ve been catching up a all the past blogs and reading everyone’s comments. I’ve noted that you’ve done quite a bit of research on supplements and take a select few, but you’ve never mentioned taking l-arginine. Is that correct? Would you mind sharing your thoughts on it?

        Some have shared they’ve had good success with it, but I’ve also read various concerning things about it, like you can imbalance other aminos, or that it doesn’t really have an effect on NO production (https://www.consumerlab.com/reviews/nitric-oxide-supplements-review/nitric-oxide/).

        My husband and I are considering taking it, but I wonder, are bone broths the better way to go?

      3. Dr. Göran Sjöberg

        Gary,

        Good to see that someone understands the essentials about nutrition. Perhaps you noted my inadequate English here. “Mouse” should read moose or perhaps elk. The weight of a full grown animal is about 500 kg here in northern Sweden.

        We are just now to put three arctic chars on the ember in our fireplace for dinner.

  37. David Bailey

    I may be wrong, but I don’t think I have seen any comment by Dr K on gluten – even though it figures prominently in other people’s discussions here. Since he seems to be a very down to earth doctor, I wonder how important he feels this problem is!

    I eat bread without any apparent bloating or other consequences.

    Reply
    1. Dr. Göran Sjöberg

      David,

      In the stores today there are, probably not without any reasons, impressive sizes of the shelves devoted to “gluten-free” products. In my present world view it doesn’t hurt to keep away from everything that spells “bread”.

      There is, as always, a lot to say about this gluten issue and here our internet is still a wonderful source to get “informed”. What “pops up” is that pesticides (e.g. glyphosate) come along with all conventional cereals you consume today and is suspected to harm the gut walls by killing the “good” bacteria that dwells there and that this opens up for protein leakage through the gut wall which links to immunological responses.

      Reply
      1. David Bailey

        I may be really naive, but of all the mechanisms by which we could be harmed, I would have thought that the action of trace residues of glyphosate on our good bacteria is unlikely. I mean we are only talking about trace amounts – and modern chemical methods can detect extremely small amounts of chemicals – and bacteria are very good at reproducing – those in the gut have to replace all of their compatriots who end up in the toilet every day!

      2. Dr. Göran Sjöberg

        David,

        Glyphosate, which is used in enormous amounts in cereal production, is today considered a “probable” carcinogen. What is hidden in the Monsanto (now Bayer) files we can just guess. As with the statins there is little industrial interest in the truth.

        It is however a fact that very few public studies have been carried out on the long term effects of glyphosate and those who have been done by independent researchers (on the low levels) seem to indicate very serious pathological effects.

        E.g. check up on French molecular biologist Gilles-Éric Séralini.

        All that I have learned during the last decade or so has turned me into a very cautious CVD person who keeps away not only from Big Pharma but also from Big Agro and with this stand I am certainly not alone today.

      3. Mr Chris

        Göran
        I too have been surprised by the lack of research into longterm effects of Glyphosphate. When people tell me how bad it is, I ask them to point me to the published research, but without success. In some circles it is an act of faith to believe all Monsanto is wicked.
        There was the WHO indication that it was probably carcinogenic, but WHO have enough skeletons in their cupboard for me to take that as gospel truth.

      4. Gary Ogden

        Mr Chris: There is very little research published on the long-term effects of glyphosate because Monsanto won’t allow it. Their own “studies” were too short-term to show much. Dr. Anthony Samsel has submitted a paper showing glyphosate residues in vaccines. Some are incubated on chicken embryos, and presumably the hens were fed roundup ready grains and soybeans. It’s not just glyphosate; when the surfactants and other adjuvants are added in the commercial product, it becomes more persistent in the harvested crops, and more worrisome.

      1. Jackie

        What a great article Errett ! It contains a couple of the things I mentioned above but SO much more ! Thank you for posting 😀 As a friend said to me recently after reading information I sent him on gluten, “It should come with a health warning!” Of course, I agree and the evidence is there. By the way it doesn’t say in the article but Dr Wm David, author of Wheat Belly, is a Cardiologist !

      2. barbrovsky

        Take a look at this article if you have time—http://paleoleap.com/what-is-wrong-with-grains/

        I did and two things occur to me: 1. It’s in the ‘genes’ of industrial capitalism. So, there are over 40,000 novel, that is man-made chemicals in circulation in our environment, none of which have been tested for human exposure. The major source? The thousands of useless products capitalism has to keep churning out as well as of course, the waste that’s created in manufacturing them. There’s only one way to put a stop this wholesale poisoning, not just of us, but the entire and it’s biosphere, and that’s get rid of capitalism, and there’s not much chance of that happening any time soon.

        And 2: The sheer complexity caused by so many chemicals impacting on us, explains why diseases of the heart can appear to have so many different ’causes’, like for example cholesterol. But add it all up and we’re living in a literal soup of chemicals and who knows how they interact synergistically as we all have different genetic makeups. It’s and nature and nurture all over again.

        It explains so many modern epidemics like asthma and autism occur, apparently without any causality.

        But so too did suppressing the facts about sugar (and paid for by the sugar industry) just as now the facts about GMOs are being hidden from the public by a government that’s effectively little more than a mouthpiece for big business. So when I go see my GP and tell her that I’ve stopped taking the statins, she is obligated by the state to warn me of the dangers. But this is not a medical decision, it’s a political decision, made by the state.

        That walking 30 minutes a day, five days a week has a better impact on health than any pills can, is never mentioned as a treatment. Effectively, health is now a business, just like any other, except of course, holds our lives, directly, in its hands.

      3. Errett

        Jackie—I read “Wheat Belly” when it first came out—and it was an eye opener for me—-I eliminated all grains from my diet (except a little cold white rice) and I can eat all the fat, protein and vegetables that I desire—-and I don’t gain weight—-164lbs—I also really enjoyed “Perfect Health Diet”. All the best to you.

      4. Jennie

        Yes me too! and you can go Gluten Free without succumbing to most of the rubbish on the supermarket ‘Free From shelves too’
        Just eat real food!

      5. mikecawdery

        Erret

        Many thanks for the link. I suspect that gluten intolerance is a distribution with coeliac disease the extreme end of that distribution. The degree of intolerance may affect other conditions to a greater or less extent. As Goran comments may be the best solution is avoid modern grains.

  38. Gary Ogden

    Dr. Kendrick: Bravo! I’ve long wondered about how ADMA fits into this picture, since it was mentioned a few Roman numerals ago. It makes perfect sense. This is why l-arginine as a supplement only helps among those with high ADMA! Looking at the diagram, one thing strikes me as odd: we pee out the SDMA, but the ADMA has to be wrestled to the mat. Why is this? Under normal circs. do we produce both, and is a balance of them necessary for metabolic health? Since I got my MacBook in July, about a third of the blogs I subscribe to are automatically sent to the junk folder, so I didn’t even know you had posted this until today. Somebody knows how to fix this, but I don’t.

    Reply
    1. Jennifer

      Gary. I have succesfully followed Dr K’s blog for 3 years now. All my equipment is ancient AppleMac. About 6 months ago I stopped receiving his notifications, and wondered what was going on….until it was suggested I look in my junk…and there they were. Am I entitled to be paranoid?

      Reply
      1. Gary Ogden

        Jennifer: I’m using a brand-new MacBook Air, and it still sends some of the blogs to which I’ve subscribed to junk. I’m not sure paranoia is warranted; more likely it is caused by stupidity. Tech people don’t impress me very much. Some are brilliant in their own specialized field, but take no notice of actual reality in its amazing breadth beyond the narrow, translucent window through which they see. What drives me nuts is that there is no owner’s manual for these things. The instructions which came with this were little more than, “turn it on.” I’m not joking. The reason I bought it was Windows 10 was so awful, the computer became almost useless. The Apple operating system is so superior to Microsoft that it is much easier to navigate, but I still want an operator’s manual.

  39. Eric

    Slightly off topic for this post:
    http://www.nytimes.com/2016/09/22/well/mind/stress-may-counteract-effects-of-a-healthful-diet.html?&moduleDetail=section-news-3&action=click&contentCollection=Health&region=Footer&module=MoreInSection&version=WhatsNext&contentID=WhatsNext&pgtype=Blogs

    What a strange study. Non-stressed women had higher inflammation markers after easting diet rich in saturated fats, but not after eating a very similar diet rich inunsaturated fats. When they were stressed, inflammation markers were the same, independent of diet.

    This supports Malcolm’s view that stress is a predominant risk factor.

    However, why would saturated fats raise inflammation in the first place? The authors take this for a no brainer, but I suspect that something else in the high-sat diet that did this.

    Reply
  40. Randall

    Lowering homocysteine level is not only good for lowering CVD. Treatment with B vitamins for 24 months significantly slowed the rate of brain atrophy (e.g. Alzheimer’s, dementia) proved with MRI Brain Scans. A method for treating mild cognitive impairment (MCI) in a subject comprising administering a therapeutically effective amount of Vitamin B6, B12, B2, and B9 which lowers homocysteine levels. An increased rate of brain atrophy is characteristic of Mild Cognitive Impairment. The mean rate of brain atrophy per year was 30% lower in the active treatment group than in the placebo group. https://www.google.com/patents/WO2012001336A1

    Reply
    1. Brian Wadsworth

      What does the need for supplementation imply about the diet of the test subjects? I suppose a nutrient-rich food intake makes supplementation unnecessary.

      Reply
      1. Randall

        look up Bruce Ames Bio and watch some of his videos on U-Tube to answer if we are getting enough from food

  41. David Bailey

    I am always curious about the extent of junk science in the modern world – I suspect its malign influence spreads further than we like to think.

    After I queried Malcolm about the threat from Gluten/wheat, to which he replied that there wasn’t much evidence, Errett gave me this link:

    http://paleoleap.com/what-is-wrong-with-grains/

    I am afraid I see a scatter-gun approach here. Blame everything under the sun, and hope some of the mud sticks!

    A big part of the ‘evidence’ in that article relates to the fact that a range of trace elements are reduced by milling and related processes. This seems to me to be quite different from a positive harm – I mean we pick up trace elements and other micro-nutrients from many food sources.

    To my way of thinking, one area of bad science, is the constant search for new hazards, often based on the fact that really tiny traces of chemicals can be detected with modern methods (assuming, of course, that these detections themselves are experimentally secure). I always wonder for example, whether due account of the Bonferroni principle has been taken in such research. To be clear, if you search for correlations between a large number of different trace chemicals and some sign of disease at the 5% significance level (or indeed one trace chemical and a large number of different diseases), you are nearly certain to find them – there is a 5% chance of any one test being spuriously positive, so if you stack up enough tests, you will almost certainly get something publishable!

    Reply
      1. Luana Lindsey

        Dr. Kendrick, thank you for this. This is why I love your work so much. You’re willing to confront the status quo, including the “alternative” status quo, yet you don’t pretend to know what you don’t. You really walk your talk, Dr. K!

    1. Soul

      I’ve looked at the popularity in eating wheat or gluten free in part as a potential way to improve ones health, but also in part being promoted to a certain extent behind the scenes by groups, which isn’t bad in my opinion.

      The idea of avoiding gluten isn’t all that new. I can remember decades ago when I first began seeing physicians for a stomach problem. In the beginning the automatic response was to try avoiding wheat for a month to see if I felt better. No testing was asked to be done. Additionally too the celiac clubs for as long as I can remember would post long list of potential autoimmune conditions linked with wheat consumption.

      I do think though that the many autoimmune conditions and diseases linked with gluten consumption has been over blown. Looking at the article, as learned from this sight and others type 2 diabetes and it’s many primary and secondary symptoms is more complicated than simply controlling glucose levels. The idea on how we treat type 2 diabetes could be incorrect. That’s big I think, not only for patients looking to improve their health, but also since it is often written that type 2 diabetes is a large growing growth area in health care costs. Then you get into cholesterol levels which reportedly improve when avoiding wheat and grains. I’m now of the opinion that cholesterol levels play little to no role in heart disease. Takings stains have more downside than upside. This morning I’m chuckling sort of as often mentioned on avoiding grains is how dental health improves. That hasn’t been the case with me, which is a rather lousy deal since I need more dental work coming up soon.

      Overall, if one feels better, looks better, and does better avoiding grains I think that is wonderful.

      The big health care elephant in the room to me now though is how we treat diseases incorrectly to often. Today we also have many items that we label diseases requiring treatment, that in my opinion are not diseases and not surprisingly treating does not improve health.

      Reply
  42. Dr. Göran Sjöberg

    Kind of interesting discussion that now has emerged here and which relates to the issue “What is science?” – a subject close to my heart. I am also happy to find several adherents to my favourite philosopher Schopenhauer here at Malcolm’s blog.

    When there are overwhelming commercial interests behind applied research and where there is incredible profits to be gained and when the research results are kept in secret files to avoid being scrutinised by independent researchers I just don’t trust the results or the entities behind.

    This insight has turned me into a cautious sceptic – especially when it relates to issues relating to my own health. E.g. with 500 million diabetics in the world who could turn “non-diabetic” by just skipping the carbs and a with a medical establishment who just doesn’t care – “Where is the science?”

    This “stinks” corruption to me!

    Reply
    1. Errett

      Three quotes from Arthur Schopenhauer—–as you know there are many others—all the best to you.

      All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.

      Every man takes the limits of his own field of vision for the limits of the world.

      Talent hits a target no one else can hit; Genius hits a target no one else can see.

      Reply
    2. Dr. Göran Sjöberg

      David,

      I should add that you are “hitting the nail” in terms of this issue of “fear mongering” or perhaps the “cautious attitude” I am adopting myself today. Why not use the safety belts if it is possible although you will probably die anyway some day?

      As do barbrovsky when he points to the incredible number of “man made” chemicals we are daily exposed to. An interesting fact here is that the linear hypothesis indicating a “safe” lower limit doesn’t materialise when scrutinised. Many chemicals has been shown to disrupt hormonal actions and where the common standard of extrapolation toxicity data (e.g. lethal dose, LD) to safe exposure limits is not relevant. This fact is today regarded as a new big “elephant in the room”.

      And I think Erret’s Paleo links well summarise the issue about modern wheat pretty well – “Just keep away!” – out of precaution. Weston Price was sweeping the floor on this matter almost a hundred years ago.

      Reply
      1. Gary Ogden

        Dr. Goran: Also, the synergistic effects of all those chemicals. Dr. Boyd Haley (emeritus professor of chemistry) conducted an elegant experiment in vitro showing how the combination of mercury and aluminum is far more toxic to neurons than either one alone. This combination occurs when a person is injected with any of the DTP vaccines and the influenza vaccine at the same time (non-live viral vaccines exported to poor countries still have the full dose of mercury, 50-75 mcg per dose), and the two breach the BBB. There certainly are many more examples which we don’t and won’t know about, since it seems all governments operate at the whim of multinational corporations, and to hell with the public.

      2. Sasha

        I have personally seen patients with vaccine shot side effects (flu) including Bell’s Palsey and temporary limb paralysis. The elderly are affected the most. None of it is ever reported as most GPs deny it’s due to the shot.

      3. Gary Ogden

        The great majority of victims compensated in vaccine court in recent years are for the flu vaccine, both infants and adults, both injury and death. Since flu virus is present in only about 16% of cases of flu-like illnesses, who in their right mind would get a flu shot? I can’t remember ever in my life having the flu. I think part of the reason is that in my generation we had only the smallpox and polio, and I believe 50-60% got DPT, but none of these were in infancy. We had all the normal childhood infectious diseases for which infants receive vaccines these days. Having these infectious diseases in childhood is important in that it primes the immune system for robust health in adulthood. Asthma was rare then, as were learning disabilities; ADD and ADHD were unknown, and the autism rate was 1 in 10,000. We have traded relatively benign childhood infectious diseases for lifelong, chronic disability. Today, according to the CDC, 54% of children have a chronic health condition, 15% have a learning disability, 9% have asthma, and the autism rate has reached 1 in 45. This is a wakeup call for Americans (and the world). Vaxxed has awaked many. The parents of vaccine-injured children are not shutting up any more. In all fifty states those parents are filing complaints with medical board about their child’s pediatrician. For much of this awareness we have Dr. Andrew Wakefield to thank. A man of uncommon courage, intelligence, and character. A gentlemanly pit bull, one of the finest the mother country ever produced.

      4. Sasha

        Gary, what you say is very true. What started off as one of the most effective inventions of modern medicine has once again turned into profit making enterprise. As soon as someone questions the current vaccination schedule, the smallpox argument is rolled out. “Do you know how many people died of smallpox”? Meanwhile supermarkets are offering 10% off your grocery shopping if you get a flu shot…

        “Science for Sale” by an EPA whistle-blower has a chapter on Andrew Wakefield and how his research been misrepresented and his career destroyed. The author is a scientist of biosolids and has no horse in the vaccination debate. He is just looking at data. I haven’t read the book yet but it looks very good.

      5. Gary Ogden

        Sasha: “Science for Sale” is an excellent book. Dr. Lewis, a scientist at the U. S. Environment Protection Agency was “Wakefielded” in order to protect the economic interests of the biosolids (treated sewage) industry. Brian Deer went after Dr. Lewis, too. Biosolids are not just human waste, but a mixture of municipal waste and industrial waste. As you can imagine, they contain toxins, heavy metals, pharmaceuticals, and pathogens. Yet the EPA allows the industry to spread this noxious stuff as “fertilizer” on farmland used to raise cattle feed for conventional diaries and feedlots. Chapters seven and eight of the book describe in detail the behind-the-scenes chicanery utilized to destroy Dr. Wakefield’s career, and Dr. Lewis’ response to the BMJ after his careful analysis of the evidence. The BMJ does not come off well in the telling. In a world where scientific research is not often replicated, the findings of the Lancet paper have been replicated on three continents, and it is now estimated that 75-90% of autism cases have some form of inflammatory bowel disease.

      6. Sasha

        Thank you Gary! I got the book recently, I will make sure to read it. It’s one of the great things about this blog – so many excellent book recommendations.

        Thank you Dr. Kendrick for putting this blog together.

      7. barbrovsky

        Slightly, but not by much, I’m off-topic but it’s rarely you see this in print:

        Doctors are the new drug dealers. Respectable and legal, prescription drugs have an air of safety around them. But they are really no different from heroin.

        From the DR Mercola Website

  43. Catherine

    Dr Malcolm – I found this fascinating, and worrying, at the same time. My husband takes a daily Omeprazole, as, after he had a massive heart attack back in March, it was prescribed along with Clopidogrel, Amiodarone, eplerenone, aspirin, dihydrocodeine, ranitidine, Ramipril, Atorvastatin, bumetanide, Apixaban, bisoprolol fumarate and probably others I’ve forgotten. It would appear that he’s been prescribed something that could, reasonably, bring on another heart attack. He suffers alternately with stomach cramps and then constipation (hence the dihydrocodeine for pains). This all seems such a concoction, and I worry that they’ll just keep giving him another drug to counteract the side effects of one he’s already taking. Could the Omeprazole be a hindrance rather than a help?

    Reply
    1. David Bailey

      Unfortunately Dr K always responds to requests like yours be pointing out that he can’t give specific advice over the internet, or he will be in serious trouble.

      I guess one idea would be to change doctors and discuss that incredible list of drugs with the new doctor!

      Reply
      1. barbrovsky

        Why the hell is he taking ranitidene and omeprazole! They do the same thing, cut acid in the stomach. Granted they do it in different ways, but both, together? It can’t be, can it?

        Dr Kendricks has already pointed out Omeprazole’s ‘side effects’, destruction of vitamins etc. I also found it addictive and difficult to get off it. It also increases aggression (you blow your top for no good reason).

      2. barbrovsky

        In what way? Well after taking it for around four years, I stopped sometime in August and suffered awful withdrawal symptoms, mostly my stomach/digestion. My GP suggested I use a smaller dose and wean myself off the damn thing. It took about three weeks/a month to get it out of my system. Now, maybe it’s maybe it’s just me, maybe it’s psychosomatic, I don’t know

    2. Jean Humphreys

      What on earth were they thinking? – answer, they weren’t. I made that twelve different types of medication, including THREE different anti-coagulants. Why didn’t they just push him through the pharmacy door and tell him to help himself to anything he fancied the name of? Tick-box medicine.

      Reply
    3. Ray Davies

      Do I understand he was given dihydrocodeine for constipation pain?
      I have had a back condition all of my life and whenever I have been desperate enough to try codeine I have had the most dreadful constipation.

      I think the idea of changing doctor seems sound.

      Ray Davies

      Reply
    4. Gary Ogden

      Catherine: My father-in-law suffered a stroke about seven weeks ago. His recovery has been amazing. He’s still using a walker, as his balance hasn’t quite recovered yet and his right leg is still a bit weak, but it seems everything else has returned, and the physical therapists are confident they can get him off the walker. They removed the clot and gave him a carotid stent. What worries me are all the dangerous drugs they’ve given him, including atorvastatin and several others on your list, plus acetomeniphen (freely available here in the U.S.). What I say will do no good, so I say nothing. One of the sweetest, finest men I’ve ever met. Standards of care are established by well-compensated drug-pushing blowhards who rise to the top of the heap, and physicians are obligated to follow them. Our state medical boards are pretty bad, though apparently not as bad as the dreaded GMC.

      Reply
  44. Janet V Martin

    So thrilled to read your latest information! NOT! I am hypothyroid and had a cardiac incident nearly a year ago resulting in two stents. After this the cardiac surgeon prescribed clopidodrel, aspirin and lanzoprazol with an added bonus of 80mg of Lipitor. I just had to decline the latter as I had been forced to yellow card 10mg treatment prescribed 9 years ago resulting inability to walk any distance which took four years to recover from ( I was lucky). It was given as a preventative. I am appalled to read this blog as I became aware that I should not take Lanzoprazol if hypo but could not get support for this from GP. I stopped today. How can a cardiologist prescribe this with these side effects. I just give up all hope.

    Reply
    1. barbrovsky

      Janet, your experience almost mirrors my own. I discovered, by accident in 2008, that I too had an underactive thyroid and was put on thyroxine. At the time my cholesterol level was 7.1 total. My then GP denied there was any connection between the thyroid and cholesterol (how wrong can you be!).

      Then in 2012 I had a heart attack and two stents fitted. I was put on Atorvastatin, Clopidogrel, Ramipril, Ranitidine, Aspirin and Bisoprol. After a few months I was taken off the Clopidogrel and put on Omeprazole.

      My cholesterol dropped to around 1! I felt awful, terrible pains would crop up all over my body, from my knees to my chest, to my shoulders and arms and they would come and go. So I cut the Atorvastatin from 80mg to 10mg but it didn’t make much difference, so eventually, in March of 2015 I stopped taking it.

      Had I known about the consequences, I might not stopped as it set in motion a chain of events that only finished (I hope) last month. Endless visits to ‘consultants’, dire warnings of impending death etc (though without a timescale). Treadmill tests, ultrasound tests. It must have cost the NHS a fortune. But to what end?

      The only good thing to come out that year-long ‘interrogation’ was the consultant asking me why I was taking Bisoprol as I had no angina, or chest pains. Of course I stopped it immediately and the weird growths on the bottom of my feet and on my head, disappeared within a couple of days!

      In October of last year, again by accident, I discovered that the NHS ran a exercise course that ran for 12 weeks, two days a week, one doing circuit training and the other day in a a gym.

      Exercise plus a decent diet is the best solution. My BP is 128/81 (I’m 71) and I weigh 61kgs and my cholesterol is currently 4.9 total (still too much for the consultant, who wants it under 4). This without those awful drugs.

      I currently take an Aspirin and Ranitidine, Ramipril (5mg) and Levothyroxine (100mg). I exercise daily (30 minute walk plus trips to the gym, I gotta reduced rate thru the NHS). I also take Vit C, a couple of grams a day, Vits D3/K2 and B12, every other day plus Beetroot extract twice a day.

      Even my GP said that I had been “over-diagnosed” and apologised for the stress I had been put through. I can’t even get a decent BP reading if it’s done by a doc, I have to do one of those 24hr things otherwise it goes thru the roof! The Heisenberg Principle cubed!

      Reply
  45. AH Notes

    I’d be more than happy to help proof reading before publication. I read all of them anyway, so there would be only a little extra time involved. Two points though, I do make mistakes occasionally.

    Reply
  46. Charles Gale

    Hi Barbrovsky

    Read with interest your account of your heart attack in 2012. Pretty much identical to me in April this year with 5 out of the 6 medicines prescribed matching yours and warnings of death if I stop too.

    Which I’m trying to do – carefully.

    Could you tell me more how you went about it…how long after your heart attack and so on? I ditched statins immediately (thus down to 5 medications from 6) and currently take 4 of these 5 on a rotation basis. Trying to find the confidence to drop down to 3 a day.

    I note you haven’t ditched medication completely and that you are taking various supplements too. I, too, have started on vit C having read about the lipoprotein (a)/vitamin C hypothesis on this website and elsewhere.

    Did you go through this process during your recovery?

    Did you know why you had a heart attack? Or had a theory/suspicion?

    It’s hard to know how to fortify oneself for the best when there’s no identifiable cause..

    Hope you don’t mind the questions.

    Regards

    Reply
    1. barbrovsky

      Hi Charles,
      Yes, in fact, about a month or so before I had an identifiable attack, I actually had one that I didn’t recognise. Unlike most attacks (I think), I had no pain, I just felt like death warmed over and burning sensation across the top of my shoulders. Both times and nothing else.

      The first one occurred on a bitterly cold night, I hadn’t eaten and I went to see a documentary that really annoyed me and it was after that it happened. It was only when I went through the stent process that the doc told me about the first one. Blood thickens if you are cold and it retreats to your core.

      The one that put me in hospitable actually occurred in the doctor’s waiting room. I’d already seen the doc because I was worried about my heart (a racing pulse basically) but he told me not worry, everything was fine (he didn’t examine me).

      So I left, went to pick up my medicine round the corner and it started in the chemists, so I staggered back to the surgery and conveniently collapsed there. The entire process of ‘fixing’ me took a hair under 10 minutes would you believe but then I spent four years in the proverbial wilderness, without any support whatsoever. As I said before, I found out about the exercise regimen by accident, my gp didn’t tell me it existed.

      But I dutifully took all the drugs they gave me without question, I suppose driven by fear really, that if I didn’t, I’d have another heart attack. This was compounded by the fact that the specialist whose care I was under in the hospital told me I had a 50/50 chance of having another one. This in spite of the fact that by then (six months later) my cholesterol was at about 1. So what is it about ‘if I don’t take my statins I’ll have a heart attack’?

      Frankly, I was never happy taking any of the drugs as I wasn’t actually sick and it seemed to me that there had to be an alternate solution as it was the way I’d lived that clearly contributed to the attack (eg smoking for 50 yrs and ending up in a sedentary role as a writer, so no exercise). I’d given smoking about two years before and I’d always had what I felt was a healthy diet (no junk food, no processed foods, or sodas and I drank rarely).

      But the statin gave me so much grief that I had to stop it which as I said, set in motion a chain of events that were essentially pointless and extremely stressful.

      I think the turning point came when I got on the exercise course and then signed up to the gym and then started looking at alternatives to the drugs I was taking. But this situation took over four years to get to!

      I’d never bought into the cholesterol hypothesis, it just didn’t seem logical that chemicals that exist in every cell in the body and that you’d die without them, could be the cause. It just didn’t make sense. So I started reading up a lot and then after a just a couple of months of gym workouts, my cholesterol was down to 5.1. So the exercise worked (I also lost over 7 kilos, not that I’m big to start with but it was the most I’d ever weighed, 67ks). And I felt better, a lot better. I could walk further with less pain and a much quicker recovery time.

      Do I need the Aspirin and the Ramipril? Well the effects of Aspirin are not easy to measure but BP obviously is. My Gp advised against stopping the Ramipril, even though my BP is ok (I’m not out to become an athlete) and as it doesn’t appear to have much in the way of side effects (a tickling cough) and now I’m back on Ranitidine, after my stomach gets acclimated, I it shouldn’t bother me too much I hope.

      The Thyroxine is a whole other story and I ain’t about to go into it here.

      I’d started on the Vitamins before I found this site and I read through ALL 21 is it? essays by the doctor and it made good sense to me and good to read too, which came as a surprise.

      I then started reading through the comments and Swedish doc hanging out in the Boonies somewhere, made a lot of sense. Does the Vit C make a difference or any of the vitamins?

      Well, it’s like the specialist lipid nurse I was sent to see and whose job it was to get me back on Statins. When I asked her how much time I’d get if I took the damn things, a week, a month, a year, she obviously couldn’t answer.

      My father died of a heart attack aged only 47. He was fit, didn’t smoke, drank rarely, went swimming in the open air pool near us, in winter. He was a fit man. What killed him? Who knows?

      As part of the year-long attempt to get me back on statins, they sent my DNA off to see if I had the three (identified) ‘heart attack genes’. I don’t. I was actually more interested in where my ancestors came from, but they didn’t test for that.

      Getting caught up in the health industry was bad for my health and it reflects a society where everything has been reduced to nothing more than a commodity, including our bodies AND our brains. Taking pills is part of it, just as the never-ending buying of crap we don’t really want or need is central to the capitalist system.

      I think what emerges here in the discussions is a sense that our society is broken and one of the symptoms is dis-ease. But hey, what do I know, I’m not a doctor.

      Reply
      1. Antony Sanderson

        +Barbrovsky
        I was given Ramapril after I started having periodic arrhythmia in my heart and had a rapid heart racing episode – (I suspect I was working up to a heart attack that never matured). I dutifully took the Ramapril but I felt awful, and whenever I stood up too quickly I nearly blacked out. My base BP all through this was never higher that 112/65 . . . I used to joke that BP was the only part of me that really worked . . the last thing I felt I needed was something to lower my already low blood pressure Told the doctor I was foregoing the Ramapril . . . He said it does other things but went along with the decision.

        Also was given a beta blocker to take . . Bisoprolol I think. It was supposed to control the arrhythmias. It made not a jot of difference, so when I read a report of an estimate of thousands of deaths across the EU over 5-6 years because inappropriate use of beta blockers, they went into the bin as well.

    2. barbrovsky

      PS: I forgot to mention that the writings of Jonathan Miller on the subject of dis-ease is worth checking into, especially ‘The Body in Question’. Grab him on Youtube:

      Reply
  47. Leon

    The BIG question is: Are Citrulline and Arginine the solution?
    There are researchers who think that these amino acids can stimulate the growth of some cancers that can’t synthesise these amino acids themselves and depend on external supply. In fact,
    Also see: https://www.ncbi.nlm.nih.gov/pubmed/18473854
    With regard to this study, the question remains: is Citrulline safe to take or is it imagineable that there are cancers that can utilise citrulline?

    Reply
    1. barbrovsky

      Yeah, I’ve tried them all, well not all but how do you tell if any of it is any good? Have your BP taken every week and a blood test at the same time? They don’t even have a way of measuring whether Aspirin works as expected, not one that’s readily available anyway.

      Does the Vit C I take every day, do what it’s intended to do? In the final analysis, you can only get a negative answer ie, when you die and even then did you die ‘earlier’ than you would have otherwise (having not taken whatever)? It’s a nonsense to talk about the efficacy of these supplements as they’re not actually attempting to treat a disease. In fact, they’re part of a ‘life-style’, which is fine, I’m not knocking it, I do it myself. But at the end of the day, i think it’s diet and exercise plus genes. As the Doctor said, you can smoke all your life and not get cancer.

      I think the biggest effect I’ve had on my blood pressure and cholesterol, has been exercise but I can’t prove it per se as I’ve been downing all kinds of supplements, playing around with my diet and perhaps, who knows, under less stress because I’m attempting to retrieve my life from the corporate NHS?

      Reply
  48. Charles Gale

    Hi Barbrovsky

    Kind thanks for the detailed reply – it’s 5 months since my cardiac event and very similar to your story.

    Know what you mean about the health service – my standard answer when asked how I’m feeling is “terrible – ever since I came to in intensive care I’ve felt terrible”.

    Felt fine before! Even have my doubts about what happened – did they diagnose correctly? Who knows – don’t have the energy to go down that route yet.

    Anyway, I’m reading through all the blogs on this website – upto Christmas 2015 – and finding it amazing, informative and running the gamut of emotions from sadness to laughter.

    I’ll continue to experiment carefully with reducing the medication, and Dr K’s just blogged about a new book to read.

    Thanks again

    Reply
    1. barbrovsky

      This is the paradox of modern medicine. My heart got ‘fixed’ in under 10 minutes but where was the followup? The treatment I got was excellent. Even the food was okay. I can’t knock it. But the nurses were all overworked and stressed out, and this was in 2012 before the latest catastrophes inflicted on the NHS by the barbarians really bit. One nurse, when I talked to her about her job, burst into tears simply because she couldn’t do her job to kind of standard she was trained to do! She felt she was endangering the health and lives of her patients.

      But I wish I’d found this site in 2012!

      And I went through the same, only worse, with my thyroid ‘treatment’, I use the word advisedly. And the nightmare lasted for about three years, I think because my body was trying to adjust to the hormones I was taking. I finally woke up one morning, literally as if waking from a bad dream. I never once got any kind of help from my GP and he suffered from an under-active thyroid as well!! It was only much later that I discovered more about treatments, not that they’re available on the NHS.

      That’s what I find refreshing about the Doctor’s writing here, he opens doors for us.

      Reply
  49. Ron Logan

    Dr Kendrick. I’ve been a reader of yours for 15 years. A doc friend just sent me a meta analysis proving the great benefits of statins and saying the claims of side effects are wrong. I don’t believe any of this, but I suspect any doctor reading it would be sold. It’s beyond my level to critique and I wonder if you would be interested in seeing it and offering comments. If so, can you give me an address to send it?  Thank you, Ron Logan

    From: Dr. Malcolm Kendrick To: amove@yahoo.com Sent: Wednesday, September 21, 2016 3:55 AM Subject: [New post] What causes heart disease part XXI #yiv7294670088 a:hover {color:red;}#yiv7294670088 a {text-decoration:none;color:#0088cc;}#yiv7294670088 a.yiv7294670088primaryactionlink:link, #yiv7294670088 a.yiv7294670088primaryactionlink:visited {background-color:#2585B2;color:#fff;}#yiv7294670088 a.yiv7294670088primaryactionlink:hover, #yiv7294670088 a.yiv7294670088primaryactionlink:active {background-color:#11729E;color:#fff;}#yiv7294670088 WordPress.com | Dr. Malcolm Kendrick posted: “Now, when I say that CVD is complicated, I suppose I mean it. Here is a slide that I have been pondering for a couple of weeks. It comes from a paper called ‘DDAH Says NO to ADMA.’1 And that gets my official ‘acronym title of the year award’. Something th” | |

    Reply
  50. Eugène Bindels

    I am on the waiting list to have a CABG (bypass). My LM (Left Main) artery has a 70% stenosis right at the branch with the LAD and RCX. So a high risk location. My previous CT calcium score was high, so the plaque is at least a stable one. Had a FFR measurement: LAD 0,55 and RCX 0,74. Planned is an OPCAB using the octupus method. Both the LIMA and the RIMA are to be used to make sure both vessels will get enough blood in the future. Advice is welcome.

    Reply
    1. Gary Ogden

      Eugene Bindels: Do you have heart-disease symptoms? I have no expertise or training in this field, but I would strongly suggest you go to the fat emperor blog and read and watch the interviews he has done over the past several months. A high CAC score is worrisome, especially if it increases over time, but it can be reduced by dietary intervention. Best wishes to you.

      Reply
    1. JDPatten

      Yeah! I’d really like to know as well. But, if CAD is not caused by cholesterol, is this rebound effect nothing worry about??

      Reply
      1. barbrovsky

        I’m still not clear about the role of cholesterol in heart disease. If, as has been stated here (and elsewhere), cholesterol is part of the body’s defence mechanism, then a raised cholesterol (raised from what though, that’s the problem?) surely should indicate inflammation caused by something else eg, smoking, sugar, junk, alcohol, stress, who knows, that prompts the body to produce the cholesterol to ‘patch’ the damaged artery, and it’s this ‘patching’ that causes the blockage? Is this correct or am I missing something?

        And why is it so difficult to ascertain the ‘normal’ cholesterol level of the body? And worse still, there appear to be three different kinds of cholesterol. The good, the bad and the ugly?

      2. Mr Chris

        Hello Barbrovsky,
        The average untreated cholesterol is, I think between 5 and 5.5
        Since thats my level, I suppose I’m doing OK. Tried to convinced the lipids specialist of that, but we were talking entirely at cros purposes.
        Dr K, are the figures I give right?

      3. Dr. Malcolm Kendrick Post author

        Approximately. The average cholesterol level, for example, in Switzerland is 6.4mmol/l (or it was last time I looked). Switzerland has the second lowest rate of death from CHD in Europe. Second only to France, and the rate of CHD is about 1/3rd that in the UK.

      4. barbrovsky

        5.5 eh? So why does the NHS advocate a level below 4?! Mine is currently 4.9 (well it was three weeks ago) but not low enough for ‘my’ consultant. A couple of months before it was 5.1. What is the basis for the 4.0? Is it because everyone over 4 gets heart attacks? I think not. It just seems a very, very crude way of measuring something whose connection to the actual disease seems vague and extremely complicated.

        IN the last analysis, it’s not a medical decision at all! It’s a political/economic one, made by the government! Which is why, even if my GP has qualms about the role of cholesterol, she can’t say a damn thing that contravenes the dogma! Which is why the Dr Kendricks can only opine! What a way to run a ‘health’ service!

  51. Gary Ogden

    Eugene Bindels: Perhaps you’re body was saying: “Thank you very much. I really, really needed that stuff!” As a long-time long-distance runner I learned to listen to my body. Athletes are prone to injury, as they sometimes push themselves beyond their limits. The result of this discovery was fewer injuries which healed faster. I would suggest that you pay no attention to the man behind the curtain.

    Reply
  52. gollum

    Yes, arginine. Unfortunately there is at least one study where it did not help

    Schulman Becker Kass et many alJAMA. 2006;295(1):58-64. doi:10.1001/jama.295.1.58.

    I was very suspicious because it went so against my bias – I mean, priors. I could not quite put my finger on it what seemed to be wrong.

    Disclosure: I am on a 2×5 g regime.

    Reply
  53. Gordon Ferris

    Does dehydration cause strokes? Plenty of research shows that some 50% of strike victims admitted to hospital are dehydrated and that stroke outcome is worsened relative to the degree of dehydration. My personal experience is that I spent a week skiing at altitude in the Rockies, flew back overnight to London on Saturday morning and began to experience stroke symptoms on Sunday. The hard exercise and flight would have dehydrated me and I foolishly contributed to the poor levels of fluid by drinking wine on the flight. I was finally admitted on Thursday and diagnosed with an Ischaemic stroke [right pons]. I am aged 67, fit, don’t smoke, slim, no diabetes, and not on any medication [e.g. statins]. Examination [CT scans, MRI, heart monitor etc ] disclosed nothing untoward except some arterial calcification relevant to my age.
    Dehydration clearly worsens stroke outcomes, but could it be causal? We are advised to keep hydrated, but I’ve never seen any special reason given. Why is this information not heavily publicised?

    Reply

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