11th December 2019
Several people have asked me to comment on a recent Lancet paper ‘Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.’ which made headlines around the world. Here – for example – from the BBC website:
What did the researchers find?
People should have their cholesterol level checked from their mid-20s, according to researchers. They say it is possible to use the reading to calculate the lifetime risk of heart disease and stroke.
The study, in The Lancet, is the most comprehensive yet to look at the long-term health risks of having too much “bad” cholesterol for decades. They say the earlier people take action to reduce cholesterol through diet changes and medication, the better.
They analysed data from almost 400,000 people from 19 countries and found a strong link between bad-cholesterol levels and the risk of cardiovascular disease from early adulthood over the next 40 years or more.
They were able to estimate the probability of a heart attack or stroke for people aged 35 and over, according to their gender, bad-cholesterol level, age and risk factors such as smoking, diabetes, height and weight, and blood pressure.
Report co-author, Prof Stefan Blankenberg, from the University Heart Center, Hamburg, said: “The risk scores currently used in the clinic to decide whether a person should have lipid-lowering treatment only assess the risk of cardiovascular disease over 10 years and so may underestimate lifetime risk, particularly in young people.” 1
The Daily Mail in the UK was a bit more excitable in its reporting
‘Adults ‘should have their cholesterol checked at 25’ because slashing it in the mid-30s can drastically reduce the risk of heart attacks and strokes
Researchers predicted huge 30-year risk profiles for heart disease and stroke, they found higher cholesterol in under-45s is more dangerous than in over-60s Even young people with healthy lifestyles ‘may benefit from knowing their risk.’ 2
My first thought, as always, is to look for the conflict of interest statement, just so you know how independent the researchers may be and make an estimate of potential bias.
My second thought was that this study did not look at cholesterol levels, or HDL levels, it looked at non-HDL cholesterol. An interesting thing to study. This is every form of liver derived lipoprotein that is not HDL, otherwise known as ‘good cholesterol’ or simply high-density lipoprotein.
Part of the reason for not looking at LDL, is that LDL is very rarely measured, or reported. Because the only way to measure LDL accurately is through ultracentrifuge, which is time consuming and expensive. Normally, the LDL levels are simply estimated using the Friedwald equation. To quote from the UK GP Notebook
‘… the ultracentrifugal measurement of LDL is time consuming and expensive and requires specialist equipment. For this reason, LDL-cholesterol is most commonly estimated from quantitative measurements of total and HDL-cholesterol and plasma triglycerides (TG) using the empirical relationship of Friedewald et al.(1972).
[LDL-chol] = [Total chol] – [HDL-chol] – ([TG]/2.2) where all concentrations are given in mmol/L (note that if calculated using all concentrations in mg/dL then the equation is [LDL-chol] = [Total chol] – [HDL-chol] – ([TG]/5))’ 3
*TG = triglyceride
This means that the researchers will not have had any data on LDL levels for most people. The difficulty of directly measuring LDL is the reason why the risk calculators used in the UK and US do not even include LDL. These calculators are Qrisk3 https://qrisk.org/three/ and cvriskcalculator http://www.cvriskcalculator.com/
So, it is important to note that this was not a study on LDL levels. Instead, it was a study on non-HDL levels. Which changes it into something completely different than was reported. Obviously, non-HDL levels bear some relationship to LDL, in that a higher LDL level will tend to raise the overall non-HDL cholesterol level.
However, and very importantly, non-HDL also includes the triglyceride (TG) level. Or at least the TG level divided by 2.2. This is important because a high triglyceride (TG) level, divided by 2.2 or not, is a strong indicator of insulin resistance, which leads to type II diabetes. Here is what WebMD has to say on the matter
‘High TG’s signals insulin resistance; that’s when you have excess insulin and blood sugar isn’t responding in normal ways to insulin. This results in higher than normal blood sugar levels. If you have insulin resistance, you’re one step closer to type 2 diabetes.’ 4
Insulin resistance, whether or not it has developed into type II diabetes, greatly increases your risk of both CVD and overall mortality, as outlined in the paper. ‘Triglyceride–to–High-Density-Lipoprotein-Cholesterol Ratio Is an Index of Heart Disease Mortality and of Incidence of Type 2 Diabetes Mellitus in Men.’
‘This study shows that a high TG/HDL-C ratio in men is a predictor of mortality from CHD and CVD. The TG/HDL-C ratio had a significant and higher HR [hazard ratio] for mortality from CHD and CVD than was found for the TyG index [fasting blood sugar]. These 2 measures, TG/HDL-C ratio and TyG index, similarly predicted incidence of type 2 diabetes, but the HR associated with a high TG/HDL-C seems to make the ratio a preferred single parameter of measurement.’ 5
You will get no argument from me that a high triglyceride level is going to indicate the underlying metabolic catastrophe that is insulin resistance. This, in turn, is going to greatly increase the risk of CVD and early death. But this will have nothing to do with the LDL level. So, it has nothing to do with ‘bad’ cholesterol. Instead is to do with triglycerides.
Therefore, this study is like looking at people who smoke, and who eat red meat, then stating that red meat consumption and smoking cause lung cancer. You have arbitrarily rammed two things together without making any effort to decided which causes what. Scientific nonsense.
There also some massive statistical problems with this study. Where, for example is overall mortality? Not mentioned. Not mentioned means it will not have been significant. Also, the use of a very wide and fuzzy ‘combined end-point.’ I have written about this many times, in many different places. It is a game played to claim statistical significance, where none really exists.
To try and explain as quickly as possible. The most powerful end-point is overall mortality i.e. how many people were dead in either group. Or, to be more positive, how many people were alive in either group.
After this come end-points of decreasing importance. For example, how many people died of CVD. This is clearly important, but if more people died of CVD in one group, yet they were less likely to die of cancer, the overall mortality could remain the same in both groups – even if CVD mortality were lower in one.
Group one
- CVD deaths 150
- Cancer death 150
- Total deaths/mortality 300
Group two
- CVD deaths 180
- Cancer death 120
- Total deaths/mortality 300
Net benefit = zero. But such results can often be hailed as a massive success for, say, a drug. For example, the ‘FOURIER’ study on Repatha (injectable LDL lowering agent) was hailed as a great success, despite overall mortality being higher in the Repatha arm. How, you may think, was this possible?
Well, the Fourier study had five end-points. Known as a ‘combined end-point’. [Mortality was not one of them.] The primary end point was the combined total of:
- Cardiovascular death
- MI (myocardial infarction)
- Stroke
- Hospitalization for unstable angina
- Coronary revascularization
How can you have five different end-points as a primary end point? Well, you just can… apparently. 6
What you may notice, or maybe not, is that three of these are clinical events: cardiovascular death, MI and stroke. Two of them are clinical decisions. To admit someone to hospital for unstable angina, and to carry out a coronary revascularisation. Revascularisation is, essentially, putting in a stent to keep a coronary artery open.
So, the second two end-points are potentially subject to significant clinical bias. If someone has a low non-HDL cholesterol level, the decision may well be to not admit to hospital for unstable angina, and to not carry out coronary revascularisation. Why, because the physicians think they are protected by their low cholesterol.
[Guess which end-point dragged the FOURIER study into statistical significance.]
You think that clinical decisions are all objective. Then ask yourself why all clinical trials, wherever possible, are double-blinded (neither the patient or the doctor knows who is taking the drug, or the placebo)? This double blinding is considered essential to remove clinical bias. No blinding, bias introduced.
Even if you look at MIs and strokes, this diagnosis is less certain than you might wish. I have had many patients where it is entirely unclear if they have actually had a stroke or a heart attack. With a small stroke it is often, simply a guess. Low cholesterol, I guess not a stroke. High cholesterol, I guess that it is.
Just in case you think I am now talking nonsense, as I was writing this blog, I was sent a BBC report of a clinical trial done on stents in the US, which stated that stents were as safe as bypass surgery, with regard to MIs. However, the researchers decided to use a completely different system for diagnosing MI…
‘The trial called Excel started in 2010 and was sponsored by big US stent maker, Abbott. It was led by eminent US doctor Gregg Stone and aimed to recruit 2,000 patients. Half were given stents and the other half open heart surgery. Success of the treatments was measured by adding together the number of patients that had heart attacks, strokes, or had died.
The research team used an unusual definition of a heart attack, but had said that they would also publish data for the more common “Universal” definition of a heart attack alongside it. There is debate around which is a better measure and the investigators stand by their choice.
In 2016, the results of the trial for patients three years after their treatments were published in the prestigious New England Journal of Medicine. The article concluded stents and heart surgery were equally effective for people with left main coronary artery disease.
But researchers had failed to publish data for the common, “Universal” definition of a heart attack. Newsnight has seen that unpublished data and it shows that under the universal definition, patients in the trial that had received stents had 80% more heart attacks than those who had open heart surgery.
The lead researchers on the trial have told Newsnight that this is “fake information” 7
When is a heart attack not a heart attack? When it is measured by investigators in the clinical study – who have financial conflicts of interest.
Another problem is that, if you carry out a coronary artery revascularisation, there is a fifty per cent chance of triggering a heart attack. Usually pretty small and not clinically significant – but an MI, nonetheless. So, for each two additional revascularisations, you may get one more MI. Which further skews the statistics. [Not an issue in the FOURIER study where only the first event was counted].
Anyway, I hope you are getting the general message that a quintuple combined endpoint is, primarily, nonsense. Full of potential bias, particularly in an observational study. As the Lancet study was.
Finally, because I have run out of energy to spend another minute looking at this study, there is the issue of Lipoprotein(a). Otherwise known as Lp(a). This too forms part of the non-HDL cholesterol measurement.
Lp(a) and LDL are identical apart from the fact that Lp(a) has an additional protein attached to the side called apolipoprotein(a). This protein has a critical role in blood clotting and therefore Lp(a) can be viewed as a pro-coagulant agent – makes the blood clot bigger and more difficult to break down. Higher levels have long been linked to an increased risk of CVD.
Just to choose one quote from many thousands of studies about Lp(a): ‘Lipoprotein (a) and the risk of cardiovascular disease in the European Population: results from the BiomarCaRE consortium.’
‘Elevated Lp(a) was robustly associated with an increased risk for MCE (major cardiovascular events) and CVD in particular among individuals with diabetes. 8
Yes, you will have spotted the link with diabetes a.k.a. insulin resistance. So, a higher triglyceride level, added to raised Lp(a), further increases the risk of CVD.
So, with non-HDL cholesterol and Lp(a) we have another massive confounding factors built into the measurement. Again, I absolutely cannot disagree that raised Lp(a) increases the risk of CVD. I have written about it many, many times. Non-HDL cholesterol is a measure that contains Lp(a) within it…. You probably get the drift by now.
The whole paper, in my opinion, is complete nonsense. Assumptions, built on bias, built on a measure that has nothing much to do with LDL, or ‘bad’ cholesterol. Zoe Harcombe did a more forensic dissection of the paper. I like her ending:
‘The researchers assumed that a 50% reduction in non-HDL cholesterol could and would be achieved. The researchers assumed that a mathematical formula for risk reduction could be applied to that assumed 50% reduction in non-HDL cholesterol. The researchers’ assumed formula included the variable “number of years of treatment” and hence the formula produced a higher number, the earlier treatment started. The assumptions made it so.
The final paragraph of the paper stated: “However, since clinical trials investigating the benefit of lipid-lowering therapy in individuals younger than 45 years during a follow up of 30 years are not available, our study provides unique insights into the benefits of a potential early intervention in primary prevention.”
No, it doesn’t.’
Yet, there was no controlled clinical trial data to back this all up. There are only models and assumptions. Yet it made headlines around the world, as such stuff always does. Not only that, it made the wrong headlines.
As the BBC website stated: ‘The study, in The Lancet, is the most comprehensive yet to look at the long-term health risks of having too much “bad” cholesterol for decades’ Bad cholesterol is the bonkers, unscientific term that is used to describe LDL. This study did not look at ‘bad’ cholesterol… Scientific journalism at is finest.
My analysis. Crumple, throw, bin… forget.
1: https://www.bbc.co.uk/news/health-50648325
3: https://www.gpnotebook.co.uk/simplepage.cfm?ID=x20030114211535665170
4: https://www.webmd.com/cholesterol-management/diabetes#1
5: https://jim.bmj.com/content/62/2/345
6: https://ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.034309
7: https://www.bbc.co.uk/news/health-5071515
8: https://academic.oup.com/eurheartj/article/38/32/2490/3752512
Dr. Malcolm Kendrick 
Thank you
How the hell does the ‘average’ Joe or Jane make any kind of sense of this mass of numbers and so-called statistics? I’m fading out on this stuff and just getting on with my life. The ‘end product’, numbers are effectively meaningless to me and I suspect to 99% of the population. There’s something obsessive, fetishistic about the entire ‘medical’ fantasy but then that’s what capitalism is, a damn fetish!
It provides a good living to a remarkable number of people – along with the illusion that they are productively employed. After all, they are doing science! (“You got an -ology???”)
That said, the more obscure the better. Don’t want plebs rocking the boat, do we?
Have you heard of F.A. Hayek?
Hayek? Old school economist I think.
I don;t think there;s any need to make sense of it – our bodies are perfectly designed to look after themselves, depending on sufficient good food, water, rest and sunlight
Seeing a doctor is the most dangerous thing you can do to yourself
Simply refuse all medications (including vaccines) unless in an accident or emergency (or suffering from an incredibly rare and dangerous illness)
Great critique Malcolm, most people would have taken this report at face value
Thank you once again, Dr. K. As ever, when it comes to the population’s health, it seems that it’s all about the money. Industry sells ( and shovels tons of b.s.) at our expense. Keep banging the (not very) common sense drum. There are increasing numbers of us willing to listen to you and Zoe Harcombe etc.
I find it marvellous that, in this sinful, self-engrossed, dishonest human world, all it takes is one single person who is dedicated, honest and competent to enlighten all of us who wish to hear him.
In my mind I am gradually building up a “society of honest people”. Dr Kendrick is a founder member, along with Dr Richard Feynman, Isaac Newton, Jean-Paul Sartre, Albert Camus, Socrates, Cicero, Gautama Siddhartha and other shining names.
Well The Lancet has a track record of dodgy papers being happily accepted without (presumably) intelligent peer review and I’m living in its vortex. Messing around with endpoints, dodgy stats & COIs abound in The PACE Trial and still Richard Horton won’t retract it! It’s an old boys network, ditto at BMJ. I now assume that anything in either publication (or associated publications) can’t be relied upon. Once bitten etc. See http://www.virology.ws/2015/10/21/trial-by-error-i/ as your starting point.
I am not a fan of the Lancet, which seems to have been assimilated by the Borg. However, the BMJ is, I think, doing its best to fight against the tide of financial bias and misinformation.
I couldn’t agree. Godlee seems to be behaving just like Horton. See: http://www.virology.ws/2019/12/06/trial-by-error-fiona-godlee-doubles-down-on-lightning-process-study/
and http://www.virology.ws/2019/11/22/trial-by-error-open-letter-to-dr-godlee-about-bmjs-ethically-bankrupt-actions-2/
http://www.virology.ws/2019/09/16/trial-by-error-another-batch-of-letters-to-dr-godlee-on-bjs-lp-study-mess/
and http://www.virology.ws/2019/09/18/trial-by-error-my-letter-to-bmj-open-about-false-mus-claim/
and http://www.virology.ws/2019/03/18/trial-by-error-my-letter-to-professor-hotopf-about-bristols-school-absence-study/
More about all these concerns can be found at http://www.virology.ws/
I wouldn’t even use The Lancet to wipe. They never met money they didn’t like. The EAT-Lancet paper was backed by a huge consortium of foodlike substance manufacturers, drug companies, agrochemical makers and seed suppliers, so no conflict there, obviously. They are now whining that those uneducated yobs on social media are undermining their efforts
https://cluelessdoctors.com/2019/11/27/bad-science-social-media-chatter/
I’m unsurprised at the Conflict Of Interest on this one too. Marketing carefully designed to resemble science.
I wouldn’t count any chickens
https://www.ageofautism.com/2019/12/the-ubiquitous-prof-pollard-how-serious-is-british-medical-journal-about-commercial-influence.html
John, thank you once again for your critical input to the system. I think you are right about the chickens. I have zero trust for Ms Godlee since she put about mis-information about Andrew Wakefield, as many others in a position of influence in the so called “health service” have done. Meanwhile they trot out the weasel (seems unfair to weasels) words “vaccine hesitant”. I am not “vaccine hesitant”. There is no “hesitancy” in my complete distrust of an industry protected from liability for substances which have a strong correlation with irreparable harm to victims, sorry, patients.
Dr K brilliant analysis as always
Very useful to have these “studies” dissected to show their true benefit. The results will no doubt be seized on by the likes of Matthew Hancock to justify more unnecessary intervention for a questionable “benefit”. It probably does have a benefit, just not for the patient, or should that be “victim”?
I do hope you have sent your excellent analysis to The Lancet, even if they will anyway ignore it!
Happy Christmas.
Andrew
Very interesting, especially the conflicts of interest and the assumptions to be made to give a positive spin.
Wonderful – Says it all about ‘scientific’ journalism – you could not make this up – One expects better from the Lancet, as for the Daily drool, one would be hard pushed to expect anything better – Good laugh though. Bravo Dr Kendrick –
Thank you, Dr. K, for another entertaining debunking.
Thanks so much for the response. I was suffering some serious cognitive dissonance, so convincing were the headlines, around what I have come to understand about cholesterol. Great job – please keep it up!
Dr. Kendrick. You are a wonder, and may you never cease!
Malcolm
Once again thankyou.
It always puzzled me why,when it was the so called dangerous lipid fraction, LDL was computed and not measured. As you state LDL is what’s left after HDL and TG are taken out.
Nice to see your coagulation hypothesis fitting with the insulin resistance lipid profile.
Dr Atkins would be proud?
Neil Upton
Boom again Malcolm! Now I don’t have to do a thing on this latest debacle “study”
– just use your blog post here
– thanks muchly!
Best
Ivor
Plagiarism. I shall sue. Or else, you get the round in next time we meet.
Another thought provoking article Dr Kendrick, in what has been a busy one for heart related health studies in the media.
Having learned on Monday that I am in urgent need of a stent / surgery as my LAD artery is almost completely occluded, the Newsnight feature rounded off an ‘interesting’ day. It will be interesting to see if the Consultant Cardiologist amends his stent/ surgery view in line with the intended change of guidance likely to emanate from EACTS.
Your comments above regarding the measurement of non-HDL Cholesterol also resonated as I also learned that my last tests dating back to March showed a TG/ HDL ratio of 5.9, perhaps one indicator of why the stent is required.
As a non-medical person and having read your (and others), entirely logical challenge to the diet-heart hypothesis, I could have done with facing up to several of the key factors you all note.
As Mike Stone has wonderfully described in his book Chronic Total Occlusion, with some damage having been done, what can I realistically do to ensure history is not repeated – assuming of course that the stent works!
Roger
many would say that Triglycerides (TGs) come from carbohydrates: that de novo lipogenesis (making new fat) in the liver (aka making triglycerides) is driven by insulin as a way of disposing of surplus carbohydrate. Many show dramatic falls in TG levels with a very low carb diet; and a rise in HDL; so greatly improving this ratio; so many would recommend to you: eat a very low-carb food intake.
Dr., Sir, you are a giant.
The first thing I noticed was “They analysed data from almost 400,000 people”
As someone pointed out, if you need a large sample to show something, it means the effect is small. If they had to go to the expense of analysing as many as 400,000 data sheets to get the result they wanted, it means the effect is vanishingly small, and can probably be ignored.
Spot on, Martin!
Very much welcome your blogs in my mailbox! Because you think, question and expose and show courage in doing so.
Mind you, I am a laywoman and while I grasp the logic of your writings I do have to do a lot of rereads.
This is what struck me in your blog:
“I have had many patients where it is entirely unclear if they have actually had a stroke or a heart attack. With a small stroke it is often, simply a guess. Low cholesterol, I guess not a stroke. High cholesterol, I guess that it is.”
And I wonder why?
i was under the impression that high cholesterol levels were not by definition a risk factor for developing CVD.
Rather CVD was a matter of three main normal processes
* Endothelial damage (damage to the lining of artery walls)
* Formation of a blood clot
* Repair
going wrong, and the simplest possible model thereof being: rate of damage > rate of repair = CVD
Why then is high cholesterol suddenly a factor when concluding stroke? Have I missed something (very likely 😉 )
Yes yes yes!
Please answer that one!
It seems to be a Malcolm internal inconsistancy.
(Aren’t we given enough of that already??)
That bit wasn’t very clear. The ‘I’ was not me, it was a.doctor thinking. At least it was supposed to be.
I read it as Dr K says he intended.
Great stuff, as ever. What we need is a quick, succinct answer to the many people who read and believe these headlines. Those who know me as a disbeliever in the cholesterol hypothesis (of course they believe it as gospel) are apt to say ” Aha, what do you say to this latest study? Are you now ready to recant and take your statins?” What is the best answer?
Perhaps ask them why study after study keeps on being published to ‘prove’ that LDL causes CVD. ‘The researchers doth protest too much methinks.’ You get very few studies proving that the Earth orbits the sun.
Thanks Malcolm. I always appreciate your informed & logical way of teasing these dopey ‘research’ studies apart.
And by the way I have leaned NOT to trust anything from the BBC via your posts. It is just as infested with uninormed idiots as those folk at the lancet.
The content and balance of the BBC has fallen so low, that I decided to forego television altogether and not pay my TV license.
It is a scandal that you have to pay a license fee to watch TV even if you don’t watch the BBC any more, but I hope if enough people de-fund the BBC we might get changes.
I know the BBC isn’t what it was (apart from BBC4) but to watch tv for an hour without commercials every 10 minutes is a bit of a luxury for me.
But a Humax or other hard disk recorder. You can watch what you record when you want to watch it, not when they broadcast it and jump through the ads which takes much less time to watch, and added bonus you can pause to go make a cuppa or have a pee, Sometimes modern technology IS wonderful.
On the few occasions I actually watch live TV I am struck by the number of ads for manufactured foodlike substances, mostly low fat of course. I think the ads for Nexium are on YouTube. Do they advertise OTC statins yet?
Thanks Malcolm, more food for thought.
IF “every form of liver derived lipoprotein that is not HDL” is the problem, then bypassing the liver is a solution?
What is happening to the “bad cholesterol” up to age 45?
How important is gut/liver axis?
So Malcolm, when I have a blood test, since my Lp(a) is high, it counts as LDL. and since my ex-lipidist told me that a statin did nothing to get my LP(a) down, why did he suggest taking statins? Was he confused between LDL and Lp(a). He shouldn’t have been since he was a big noise in the European Atherosclerosis Society.
another question, Lp(a) is produced in my body, is this because the control mechanism for its production thinks I need it, or is the control system out of whack?
Answer to question one – because the only tool he has is a hammer. Answer to question two Lp(a) level is primarily genetically determined.
I have very high Lp(a), over 300 nmol/L or (different test) 125 md/dL. But I got a CAC scan (coronary arterial calcification scan) done and got a score of zero. 90% of people my age (55) have higher scores. Low carb since 1/1/14, and added intermittent and long term fasting about 1.5 years after starting.
Note also that I showed Lp(a) follows Dave Feldman’s lipid energy hypothesis.
Most smokers to not develop lung cancer.
Linus Pauling recommended vitamin c and lysine for lp(a). It’s worth looking into.
Thank you!
Ddavidson@northshore.org
Sent from Yahoo Mail on Android
Thanks, Dr. Kendrick. What on Earth possesses The Lancet to publish such rot?
$
You mean £ …
;))
Honesty. Trust. Dependability… Medicine. Splint a fracture: Sure. OK.
Anything more complex: No.
In a way, the disillusionment with the Establishment so effectively created here fosters Stress.
I strive for an open mind, questioning everything. Even here.
I see the caregivers available to me (Complex, needed care – through insurance!) as combatants in a battlefield surround. My only “weapons” are my own education and my willingness to persevere.
Unfortunately, I cannot know enough to stand secure . . . alone.
JDPatten: We all stand with you. Everyone here in this space has given me strength, and the knowledge to take charge of my own medical decisions. I nearly cried when a close family member said the only thing keeping him alive was statins. I see a definite cognitive decline. An unchangeable mind. Fear is a powerful weapon. Fear and ignorance.
Gary, 🙂
An interesting subtext of the post involves statistics. In order to confer my degree (a PhD), we are supposed to learn considerably more in the way of stats than a physician typically would. Even though I use my degree to work as a clinician, I had to take numerous stats courses and write a dissertation that was pretty dense with statistics. Now, even with this extra training, I don’t feel particularly adept at understanding or translating stats to anyone. In fact, I would be challenged to explain my own analysis in my dissertation. Which leads me to the idea that most doctors would likely be even less capable of understanding statistics than I. This leaves many of us vulnerable to a handful of clever and perhaps sometimes unscrupulous people. So thanks to the good doctor (and Zoe Harcombe) for unwrapping all of this in an understandable way.
What do you think of this guy:
https://med.stanford.edu/profiles/john-ioannidis?tab=publications
Or this one:
https://www.badscience.net/about-dr-ben-goldacre/
or this one:
https://www.medpagetoday.com/publichealthpolicy/generalprofessionalissues/67339
No thoughts on these three guys?
They are, granted, members of established medicine who, nonetheless and at their professional peril, are battling dishonesty and stupidity from within.
Give these members of the “other side” an honest hearing.
What’s to lose?
Dr Ioannidis is a giant, imo. I read “Bad Pharma” and I liked it but I consider Goldacre a bit too arrogant and mistaken in some things, but that’s just me, I might be wrong. And who is the third person?
JDPatten: Good work these three have done, although I’m no longer too keen on Ben Goldacre.
Sasha,
The third person, Doc Prasad:
http://cdt.amegroups.com/article/view/2854/3787
(And so young!)
Thank you, I will read it
Ioannidis wrote a classic paper. Prasad I’ve seen on Twitter and this article is good. Goldacre I’m not so sure about, he was very anti-low carb/keto even for diabetics, it being a “fad diet” unlike low fat, obviously.
And to think that some people provided themselves with a living writing this kind of bilge. Yu will note that I did not say “earn”.
Malcolm,
I’d really like to clarify what insulin resistance actually means. I mean presumably you measure the amount of insulin to lower the blood glucose by a given amount.
However I’d like to know what it is that goes wrong, is it that the receptors on the fat cells that would take in glucose become less sensitive, or do they reach saturation point, or what?
Always assuming this question has been resolved.
Major can of worms. I upset the likes of Jason Fung from time to time by informing him that I do not believe there is any such thing as insulin resistance. If there is such a thing, it only occurs in skeletal muscle and the liver. I sometimes think of the process as ‘trying to find somewhere to store glucose, when your glucose/glycogen stores are full.’ These stores only exist in skeletal muscle and the liver.
Anyway, imagine you have no fat cells. A rare condition that some people suffer from.
You eat carbohydrates, which are converted to glucose/fructose and sent to the liver. The liver stores about 500Kcals, the the muscles store about 1,000Kcals – you are now full of ‘sugar’ and can store no more. If you eat more, the liver can only convert the sugars to fat (nowhere else for them to go), through a process known as de novo lipogenesis. Then, the fat is sent out from the liver in triglycerides (VLDL molecules). Then, it has nowhere to go, because there are no fat cells to store the fat.
Then…. all hell breaks loose.
Every single person with the condition known as Generalised Congenital Lipodystrophy (no fat cells) has type II diabetes. Why, because their energy stores are full.
Ergo, people who develop diabetes, do not develop it because they are fat. It is because they reach their limits of energy storage. This is not insulin resistance it is just being full.
Malcolm,
Thanks for your fast response!
I have always felt that the term insulin resistance was somehow vague. However, since thin people can get T2D, does that mean that the number of fat cells in the body varies widely from person to person?
Also how do statins often raise blood glucose levels?
I understood that also skeletal muscle cells can hold intramuscular triglyceride (IMTG) and diglyceride (IMDG) in lipid droplets and can be oxidized during exercise.
So there’s a place the fats can go?
‘Skeletal intramyocellular lipid metabolism and insulin resistance’:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762133/
yes, but it is a pretty small place, compared to adipose tissue
I read somewhere recently, can’t for the life of me remember the source, that excess fat in the circulation which cannot be stored due to low insulin levels, (or general fullness) is gradually converted to ketones and then simply burnt off in the peripheral tissues, producing heat. No exercise required at all. The problem, though, is keeping cool enough, especially in summer.
I have also found personally, that proportionately very large amounts of dietary fat, eaten to keep hunger at bay on a LCHF diet, are just not digested and absorbed from the gut. I tolerate this well, but others might not.
Thank you for this explanation. I have two questions if you have time to answer:
1. Since there are plenty of fat people without T2DM and plenty of skinnier people with it (who don’t suffer from congenital lipodystrophy), does that mean that skinnier people with T2DM have an impaired ability to store energy as compared to fat people without T2DM?
2. And if that is so, does that mean that this impaired ability to store energy places this people at evolutionary disadvantage in the modern world?
Thank you
On the other hand, your description is consistent with the speed people can get off their medications after starting a ketogenic diet, radically limiting the amount of carbohydrates consumed and the amount of glucose produced.
However, following your model one would expect the insulin resistance (IR) to be resolved after about 24 hours when all glucose has been consumed and fats are starting to be ‘burned’. Either through oxidation of the IMTGs or through ketones.
Unless Randle (1963) was right with his Randle cycle[1], stating that ‘glucose oxidation was inhibited by fatty acids’. Which would require the lipids to be oxidized before intramuscularly stored glucose could be consumed.
You stated 1 Mcal can be stored in the muscles. That is from glucose. I wonder how much energy is stored in muscles which are ‘fully loaded’ with TAGs and DAGs?
[1] Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963). THE GLUCOSE FATTY-ACID CYCLE ITS ROLE IN INSULIN SENSITIVITY AND THE METABOLIC DISTURBANCES OF DIABETES MELLITUS. The Lancet, 281(7285), 785–789. doi:10.1016/s0140-6736(63)91500-9
https://sci-hub.tw/10.1016/s0140-6736(63)91500-9
Malcolm,
Sorry to labour this point, but I now don’t understand what T2D really is! I mean, first I thought it was ‘insulin resistance’, but you think that is a misnomer for a condition in which the glucose stores simply fill up. My problem is that fat people can have T2D, or not have T2D, and thin people can likewise have T2D (maybe not so likely) or not have T2D.
So does this mean that the glucose storage capacity of people varies? E.g. might it be that Generalised Congenital Lipodystrophy is more of a continuum (e.g. depending on whether people have both copies of their gene affected, or just one).
Fortunately, as of now, I am a thin person without T2D – so I don’t have a personal concern about this.
Type 2 diabetes is simply a blood sugar measurement. It is not a disease.
So what’s the disease? I’m confused.
barovsky: T2DM (and “prediabetes”) is simply called a disease so that drugs can be sold to target it.
Also a lot of disease-mongering manipulation for $$$;
Dubious diagnosis
https://science.sciencemag.org/content/363/6431/1026
A war on “prediabetes” has created millions of new patients and a tempting opportunity for pharma. But how real is the condition?
Pre-diabetes! What a crock of shit! Even my regular GP admitted pre-diabetes is rubbish and now there’s ‘pre-anaemia’ after I was diagnosed with slight lowering of the red blood cell count most likely due to the medication I was on, an anti-coagulent (not Warfarin, can’t pronounce it or remember its name)), which I pointed out to my GP at the time.
Kinda off-topic but not really:
It’s really quite obvious (to anyone who cares to look) that the explosion in diseases of all kinds is down to the explosion of novel and untested chemicals in our biosphere, thus air, water, food, soil, household crap, you name it combine to assault and kill us. If we are to survive as a species it’s clear we have to dump capitalism, the fetish of consumption, but hazard a guess that it’s already too late…
barovsky, unfortunately the intellectual pygmies that inhabit the newly elected UK government think that GMOs, 5g, vaccines (to the extent of mandatory vaccinations, and others are the things should be embraced, so it is likely to get worse. Surprising in some ways since Matthew Hancock has had conversations with Aseem Malhotra, but probably chooses those with a fat vested interest.
AhNotepad: How odd. In the U.S. it is the liberals who are promoting the tyranny of vaccine mandates, and the conservatives who are, to some degree, pushing back against them. As for 5G and GMO’s, both are shoving them down our throats.
Malcolm,
I am still struggling here! Are you really saying, people are born with differing numbers (or quality) of fat cells, and those who have a lot can absorb a lot more glucose than others, who have fewer fat cells (you have already talked about the limiting case of almost no fat cells). So roughly speaking, everyone has their own safe limit for glucose intake, and if they exceed it, problems set it.
Dr. Kendrick: “insulin resistance” is an important concept to understand. Came across this molecular explanation:
https://www.sciencedirect.com/science/article/pii/S1550413107000678#bib146
“Few physiological parameters are more tightly and acutely regulated in humans than blood glucose concentration. The major cellular mechanism that diminishes blood glucose when carbohydrates are ingested is insulin-stimulated glucose transport into skeletal muscle. Skeletal muscle both stores glucose as glycogen and oxidizes it to produce energy following the transport step. The principal glucose transporter protein that mediates this uptake is GLUT4, “
Need 2 keys to allow glucose uptake by GLUT4 into skeletal muscles, one from insulin and one from the cells. Once muscle cells are full, then liver and fat cells have to store the excess glucose. High chronic and acute glucose availability will overwhelm the system i.e. “insulin resistance”. More insulin is not the cure.
Insulin resistance really has no defined meaning. Gary Taubes considers it to be the difference between which fat cells versus muscle cells are sensitive to uptake of glucose (thus being more or less insulin resistant). That is, if your fat cells are happy to take in glucose, they are insulin sensitive, whereas your muscle cells are insulin resistant. You get fatter. If it’s the other way around (fat cells are insulin resistant, muscle cells are insulin sensitive), you don’t get fatter. That’s one way of looking at it.
I believe there is an “insulin resistance” at the fat cell level. If you read the protons thread at Hyperlipid:
http://high-fat-nutrition.blogspot.com/
He describes a theory where saturated fat makes fat cells insulin resistant, such that they don’t want insulin or glucose. Meanwhile, PUFAs like linoleic acid cause fat cells to be insulin sensitive, meaning they want more insulin and glucose. Since our intake of PUFAs has exploded, this is one plausible reason for the increase in obesity. This is a valid way of looking at insulin resistance.
In all, though, “insulin resistance” is a poorly described term. And I don’t help this. If you have high triglycerides and low HDL, I’ll label you as “insulin resistant”, which simply means it’s taking more insulin than it should to control your blood sugar. You likely have high fasting insulin or would fail a Kraft OGTT. But “insulin resistant” sounds a lot better than “too high of an insulin level, with a likely low level of glucagon, poorly controlled blood sugar, fatty liver and pancreas, degraded sugar and insulin (and glucagon) responses, etc.”. 😉
Good analysis
What about in a person who does a lot of training? His muscle cells will take up glucose because of energy requirements but that doesn’t mean that his fat cells are resistant to insulin. Isn’t that correct?
Wiki explanation of Linoleic Acid :
“Conjugated Linoleic Acid (CLA) is a polyunsaturated fat found in linoleic acid, an essential fatty acid found mostly in plant oils. … CLA helps your body build muscle rather than store fat and has anti-inflammatory properties. It may even help prevent cancer.”
That sounds like a good thing ?
Confounding stuff !
Jerome Savage: As I understand it, CLA is healthful. This is one of the benefits of pastured, raw milk. On the other hand, LA from seed oils is certainly not. None other than Ancel Keys showed that in the Minnesota Coronary (something or other). He buried the findings, and never published them, since it demolished his diet/heart hypothesis. The Sydney Heart Study also showed the danger of LA in seed oils. Pay no attention to Wikipedia.
Soul
Re blood pressure & part 58 from just over a year ago, extract as follows ;
“If you must take medication, I was a very strong supporter of ACE-inhibitors, in that they blocked angiotensin II, and increased NO synthesis. Both good things. However, some research has come out recently, suggesting they may increase the risk of lung cancer. Not by a great deal”
Of course L Citulline seems effective and without side effects. Also see the Sidney Port paper in the Lancet which analysed Framingham data and gave norms according to age. I mean supposing high BP was not really as much of a problem as sometimes a big Pharma made out?
Jerome & Soul: root cause of elevated blood pressure is not angiotensin II
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166313/
“Conclusions:
We demonstrate that hyperglycemia activated the renin–angiotensin system, induced epithelial–mesenchymal transition, and contributed to kidney fibrosis in an experimental diabetes mellitus model.”
https://jeccr.biomedcentral.com/articles/10.1186/s13046-019-1309-6
“Patients with diabetes face an increased risk of developing cancers, mainly including breast, liver, bladder, pancreatic, colorectal, endometrial cancers [7] (Table.1). This risk may arouse from special diabetic pathology, such as hyperglycemia, hyperinsulinemia, insulin resistance, distorted insulin-like growth factor-1 (IGF-1) pathway, oxidative stress, enhanced inflammatory processes, and aberrant sex hormone production [8, 9].”
It would be better IMO to think in terms of “insulin sensitivity” – fine tuning the response of receptors in different tissues to the overall insulin level and adjusting signalling.
My “insulin resistance” was obviously high – trigs/HDL nearly 7 in UK numbers, over 15 in US numbers, but presumably because I lack Phase 1 insulin I remained slim (I was very skinny as a child) and only became fat AFTER meeting a dietician. By eating the exact opposite of what I was told, I lost all the weight again and my trigs/HDL is now less than unity (less than 2 in US numbers) so I killed the IR by eating lots of saturated fat and meat. Oops!
chris c: Yup. That’s the way it goes. My TG/HDL ratio is 0.5. I have been eating only wholesome food since about 2005. My only carbs come from small amounts of fruits, potatoes and sweet potatoes, and some from other vegetables.
Gary – it seems Mr Keyes has been a very bold boy and Mr Wiki perhaps going the same way. I am aware it is subject to all sorts of bias but the world is a confounding place for the average fella trying to get to grips with his or her wellbeing. Bob Dylan once sang, “what’s good is bad, whats bad is good”
Was he singing about diet ? (I jest)
Andy – Thank U. Think I need to hire a professional reader to give me a true & fair view of the medical world
Andy
hyperglycemia “high levels of sugar, or glucose, in the blood” GP was fairly ok with my blood sugar levels. So in my case – something else ?
Jerome, does GP see only fasting BP? Checking postprandial glucose spike is better predictor of potential problems.
Sorry but I strongly disagree about “prediabetes” – I’m with David Ludwig when he says “prediabetes isn’t really pre-anything”
The diagnostic criterion for “diabetes” was set where 50% of the beta cells are dead. When only 49% are gone you are “not diabetic” but definitely not normal. EPIC-Norfolk showed that CVD risk increases linearly with HbA1c starting from a genuinely “normal” number of 5% or less, and further studies have repeated the finding.
I know a number of diabetics who have tested friends and family and found the same as Richard Bernstein, who tested meter salesmen – genuinely normal people have very tightly controlled blood glucose of around 5 +- 0.5. When the BG starts to diverge from this number you are “on the diabetic progression” which gives you plenty of time to reverse said progression. As Andy pointed out, in most (but not all) forms of “Type 2” the Phase 1 insulin is the first to go, leading to glucose spikes around 1 hour postprandial. This is a pretty big signal to do something.
I’ve seen a number of dieticians who have experimented with Continuous Glucose Monitors and seen postprandial spikes but claim that since they are “not diabetic” this means it is “normal” to have glucose spikes. No it is not “normal” just because it has become common.
I suspect I never had a proper Phase 1 insulin response since childhood, but my Phase 2 is still strong. I know a small but significant number of people with the same syndrome. Only about half of them progressed to diagnosed diabetes, the rest like me remained “prediabetic” but we all had symptoms of diabetes and conditions that are “common in diabetics” including complications like peripheral neuropathy and retinal damage.
Diabetic progression only happens because of most doctors’ insistence on high carb low fat diets.”Prediabetes” gives you the opportunity to eat the opposite and reverse the progression. Don;t knock it!
How do you determine that 50% of your beta cells are dead?
Thanks Andy – will keep in mind on my next GP expedition.
“How do you determine that 50% of your beta cells are dead?”
Simple, you get diagnosed with diabetes . . .
That’s circular reasoning, isn’t it?
Many thanks, Dr Kendrick, for educating us all over the years. And for your excellent books – almost as amusing as instructive (which is saying a great deal).
May I wish you a merry Christmas and a happy Hogmanay – and a dram or two of your favourite malt(s).
I shall raise a glass to you, at the toast “Absent friends!” Because anyone who does as much good as you do is the friend of everybody.
Nice breakdown of the latest world wide news report on cholesterol. As always for someone like me it is depressing to read. I’m ill and have been for an adult life time. Being sick it’s disheartening to learn how biased and corrupt published study information can be. This is of course information used by physicians to treat patients. One would hope the medical establishment would be on your side, the patients side, but all to often that isn’t the case.
But on the positive, having been forced to be my own trail blazer, i have been able to improve my health some on my own. Seems I have a few food allergies, that effect my colitis. One being pork and now the others being beef and dairy. Pork makes me itch all over and my gums swell up. Dairy and beef make me weak. It’s hard to exercise after eating either. The very worst, scary worst, stomach flares have occurred after eating commercial beef.
So in summary for me, with medicine being more religion than science, as shown once again with this world wide published study, I likely would have been better served if I stated my trail blazing health path by joining the major religions and following their food guidelines.
Soul/Stuart: Farmers are Pharmers
Connecting allergies, gut microbiota, antibiotics, meat, medicines, mitochondria, tight junctions, etc..
https://www.gutmicrobiotaforhealth.com/en/gut-microbiota-and-allergies/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659212/
Statins: antimicrobial resistance breakers or makers?
https://www.sciencemag.org/news/2017/09/are-antibiotics-turning-livestock-superbug-factories
Thanks Andy – probiotics, fecal transplants, food allergies, etc certainly have been a hot topic of discussion over the years for the IBD crowd. I believe now the hoped for improvements with these items has been a disappointment for many. With that said, there is a diet that some follow, the SCD diet I believe it is called. The SCD diet is low in carbs, and is rich in probiotics. The diet seems to help some people with IBD conditions. It gets some positive response. For one reason or another it doesn’t seem to be a cure. If the diet is a cure, it requires more help in other areas, such as medications to assist with healing, etc.
I guess going through my mind of late is a nephew. Bright young guy. He did excellent in school, going on to win a nice University scholarship. Here of late though he has run into quite a bit of health issues that has caused him to leave school. I’m wondering if possibly what my nephew has developed might be similar to what I have. Time will tell of course. I suspect a grandfather had the same pork allergy as me. I’ll never know for certain but he experienced similar symptoms as I but he didn’t know the cause. The beef and dairy allergy/ sensitivity, what ever one wishes to label it, is something my father might have. I only base that upon one symptom that the two of us share that is not related to the colitis. Will see of course.
With food allergies, what I’ve found interesting is transplants. From what I’ve read, when a liver is transplanted, the same food allergies the donor had in life can show up in the recipient. Possibly the liver is effected by probiotics and gut bacteria. I have my doubts though that the effect is direct.
I second that.
My question is what is the endgame for publishing this smoke and mirrors ‘research’? Is it to promote Repatha, or some new wonder drug?
Frederica, – How could you even entertain such a shocking idea ?
– What has the Medical and Pharmaceutical Industries done to create such…. cynicism ?
I am not a medical person, in fact I was a math major in school. I was a little shocked when I saw that Dr. Oz was on t.v. saying that most bypass and angioplasty doesn’t work for stable heart disease. The establishment usually trots him out to damage control. I have my doubts whether any of these bypass and stent work. If the entire vessel is damaged, which Dr. Oz, said it was, then how can going in there and disturbing the plaque be a good thing in any circumstance? Since, Dr. Oz said they didn’t know where the heart attack was happening, and sometimes it wasn’t in the most closed off place, how can going in there and stirring things up be good for any reason? I think they are all trying to save face. They were wrong about all of it. The cholesterol, the plaques and the entire thing. It’s like a long time ago using bloodletting and telling everyone it worked, when it made people worse.. I wish they could admit it so people won’t be made worse.
I’ve had two heart attacks (I’m told) seven years apart.The first one had two stents in one artery then an additional two stents were inserted into the existing artery and a new stent in a new artery after the 2nd attack. Interestingly (or not), after the 1st procedure, the doc told me that there was minor blockage in the second artery but they chose not to mess with it, it was only after the second attack that they decided it needed a stent. So, the second artery was in pretty much the same state, seven years later! Did it need a stent?
But you say they don’t work? What does that mean? The 1st procedure kept me alive for 7 years, so is this failure? What are the alternatives?
barovsky: Read what Dr. Bernard Lown has written about this issue. Also keep in mind that what is true on the population level isn’t necessarily true for any individual. In your case this treatment very well have been a good idea, although it is difficult to know.
I hav 2 stents since 2004 and so far so good. Am told almost total blockage at critical point but remained fairly active up until my wee bit of plumbing. Lots of activities since including 10 marathons, many many long distance cycles and many many 3 000 feet elevations. Angiogram some years ago at the behest of a GP concerned that I wasnt statinating, indicated no cause for concern.
Jerome Savage: Good for you. It remains true that some people will benefit, or at least not be harmed, by such interventions. I still remain very active at 70, with no cardiac symptoms, but my one marathon (at age 55) essentially ended my running career. No matter. I like hiking in the woods way better, listening to Beethoven symphonies on the drive to the mountains. The added benefit is meeting so many interesting people on the trails. I have hundreds of friends I didn’t have before. I’ll likely never see them again, but I still consider them new friends.
Gary Some concern with recent inputs on this site that suggest significant risk with stents. This was news to me & a little alarming, I assume removal is out of the question. The risk associated with bypass vein clogging, I was aware of & assumed this risk was greater than stent associated clogging. But it appears not, – P….ses me off !
It’s also good to let others like Barovsky know, that coronary stents do not mean loss or reduction in activity levels. Business as usual but with less risk (I had thought & still believe) as blood flow restrictions are removed.
I was never a competitive runner but did enjoy chats along the way in my runs. The following is a response from Helen from OZ who I arranged accommodation for as part of her bicycle tour of Europe last year, when I asked her what the highlight of her trip was. “oohhhh tough. Cuz it’s the journey not the destination right? I thought maybe the feeling of reaching the north cape (which was a fantastic feeling of achievement and carnival atmosphere as other cyclists arrived throughout the day)
But really it was the the daily little things, coffee in the tent, sunsets, alllllllll the food, experiences with people giving me glimpses of their lives. It’s just a wonderful way of being, I can’t wait to get back out there ” I can connect with all that !
Barovsky,
I am curious about your comment “(so I am Told)”.
I am vaguely aware that there are “silent heart attacks”, but I am so cynical that I seriously wonder if this is a ruse to put more people on drugs or insert stents. If I were told I’d had such a thing, I think I would ignore it!
Informed comment please!
Interestingly enough, blood letting works very well when done appropriately and not in the amounts they were doing it in the old days
Anne: re stable heart disease and Dr. Oz
Maybe a stable CAC score indicates stable heart disease and damage/ repair is in equilibrium. Stents/CABG would not improve survival for these people. Now I have to find out if my heart disease is stable.
What enrages me is how my younger GP colleagues blindly push the guidelines, for example, a female patient in her late 60s with a risk calculator score of 10.1% 10 year coronary risk ( yes, I know that they are rubbish) gets put on a statin, instead of being told that this is good news – roughly 99:1 against having a heart attack in the next year (not dying, notice), asssuming that the 1 year risk is 1/10 of the 10 year risk. You wouldn’t put a large amount of money on a horse at 99:1, but you’re willing to take expensive side effect causing ineffective ( from the mortality viewpoint) statins?
Well said, Dr K. You are like a berserker Number 8, scattering opposition backs in all directions.
Dr Kendrick
Understanding your writing is easy for me but I am likely not alone in feeling incapable of doing this analysis myself. Despite medical training.
Articles like this should be more widely available, or at least given greater exposure to the medical community, particularly international students of medicine. And your efforts are important enough to warrant financial support of a nature that frees you up to do more writing and speaking IMHO…
Have you considered seeking online (completely voluntary) donations to support your efforts at promoting this unpopular and counter culture message on CVD?
I understand, for example, Jordan Peterson garnered enormous financial support for his video messages when first presented (I think it was on Pantheon?) by simply leaving room for support from people who felt it was beneficial to them. People simply signed up and or paid what they felt it was worth to them.
Not sure how that would work for you
Selling your books might not do it 🤓
Regards and blessings
Dr Rob Pankratz
Yes, it is a good idea with Pantheon. I would contribute to Dr Kendrick’s work. Rhonda Patrick does the same thing.
Sasha: Isn’t it called “Patreon?”
Yes, that’s what I meant, sorry
Dr. Kendrick: How can TG be “non-LDL cholesterol,” or, indeed any form of cholesterol? Teacher taught us that TG are three fatty-acid molecules attached to a glycerol molecule.
Because VLDLs are normally called triglycerides. Even though they are not
Dr. Kendrick, Gary had a good question, let me reformulate: Trig mass/5 can be used be used to evaluate LDL-c, but isn’t it so that lipid panel measures separately trigs and all the cholesterol, without being able to make dinstinction of vldl / ldl. That is, total – hdl is actually all you need for non-hdl value?
Great analysis of large study, as usual.
Thanks JR
Dr. Kendrick, let me reformulate Gary’s question: is it not so, that lipid panel measures total cholesterol and trigs separately, and HDL, so you simply get non-hdl by subtracting total-hdl? no need for trigs mass/5 to guess VLDL-c in here?
Great analysis of this “study” as usually. Thanks, JR
It is difficult to establish how different laboratories measure ‘cholesterol’.
The problem with this is, that in the UK, if Dr Kendrick gained any personal benefit from such informal contributions, they would be fully taxable as part of his income, so seeking them is probably not worth the hassle.
It depends. Rhonda Patrick, an American, was collecting about 16K a month through Patreon, if I am not mistaken. Peterson, a Canadian, more than 50K a month, I think. I would assume both of them are taxed.
What! What! Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium. https://www.sciencedirect.com/science/article/abs/pii/S0021915012005229 High dose and long-term statin therapy accelerate coronary artery calcification https://www.sciencedirect.com/science/article/abs/pii/S0167527315001990
Randall: looks like statins can increases good plaque by reducing bad cholesterol, win/win.
*Causes* calcification ?
Oops !
On the bright side, stable calcification would be preferable to…’unstable plaque’
JamesDownunder: And unstable politicians! Although the Brits seem to have gotten rid of some of the dead wood, here is the U.S., the lunatics are still with us..
The vascular surgeon I saw for my peripheral arterial disease got one thing right. He told me he could implant a stent but he would rather see if I could avoid it by generating collaterals. This worked.
However he also told me I should go back on a stain to “stabilise” my plaque. When I read that “stabilise” meant “calcify” I was even less inclined to comply.
How statistical deception created the appearance that statins are safe and effective in primary and secondary prevention of cardiovascular disease
In 2015 Diamond and Ravnskov analysed three different statin trials. I’ll discuss one of them.
The JUPITER trial starred rosuvastatin (Crestor) and involved nearly 18,000 people. It used ‘combined end points’ which Dr Kendrick warns us about above.
“The primary outcome was the occurrence of a major cardiovascular event, defined as nonfatal MI, nonfatal stroke, hospitalization for unstable angina, arterial revascularization or death from cardiovascular causes.”
Note that a nonfatal heart attack and a fatal heart attack were both classed as a primary outcome. The fatal heart attack wasn’t given more weight than a nonfatal heart attack.
Also note, as Dr Kendrick says, that it is sometimes unclear whether someone has had a heart attack or a stroke; and it is a clinical decision whether someone needs hospitalization or revascularization (stent or balloon angioplasty). So there will be marginal cases where it is the researcher’s opinion rather than objective facts that determine if an end point has been reached.
Now this shouldn’t matter because the study is double blind. In theory, nobody knows who’s on statins and who’s on placebos. Except in practice the statins lower cholesterol so much that as soon as you see the cholesterol scores you know who’s on statins, as Dr Kendrick pointed out some time ago.
Thus it would be relatively easy for interested parties to favour the statin group by tipping marginal decisions in a certain way. I’m not saying they do it, but the temptation must be there.
Anyway, the trial was stopped early and trumpeted as a huge triumph for statins with 251 primary endpoints in the control group versus 142 in the rosuvastatin group. The number of fatal and nonfatal heart attacks combined was 68 in the control group and only 31 in the rosuvastain group, allowing the makers to claim ‘more than 50% avoided a fatal heart attack’.
But when Diamond and Ravnskov dug into the data they discovered “there were 11 fatal heart attacks in the treatment group, but only six in the control group.” [my bold]
So the reality is that while rosuvastatin might reduce the incidence of nonfatal heart attacks, it doubles your chances of dying from a heart attack.
There were also more cases of diabetes in the statin group. The authors conclude: “An objective assessment of the JUPITER findings should therefore be conveyed to potential patients in the following manner: ‘Your chance to avoid a nonfatal heart attack during the next 2 years is about 97% without treatment, but you can increase it to about 98% by taking a Crestor every day. However, you will not prolong your life and there is a risk you may develop diabetes, not to mention other serious adverse effects’”
Martin Back: Thank you for reminding us of this. Cunning they are not. Neither are they scientists. Makes me wonder of they are aware they are publishing bilge.
Martin,
Thank you for this “reminder”!
If this is not a “maffia-type”, criminal behavior behind the scenes to kill people for the profits with legal drugs (one third of all deaths related to these drugs?) I don’t understand what criminality is.
Peter Goetsche wrote a serious book about this and has paid a high price for his openness.
https://www.deadlymedicines.dk
Scary reading though!
Yes, very good book. He has another one on futility of preventative mammograms. No wonder they hate him so much…
Well lets be brutally honest, the greedy Pharma guys are looking at ways to increase their market share with their most profitable drug of all time. They have infiltrated the over 40’s so logically its time to open up the kids market. Here’s a thought, if all of this nasty cholesterol is coming from our liver then why not simply remove 95% of it from birth!
That aside, its pretty obvious to me that there is so much money in this wonder drug that there will be justification for everyone to be given a statin from birth in the next coming years.
I’d like to see an honest report that shows the TG level of everyone who is admitted to hospital with cancer, diabetes or CV events – I would bet that those results would be quite startling – so much so that they would be quickly buried.
I think it was Zoe Harcombe who pointed out you have to be in stains to be eligible for PCSK9 inhibitors
I need new glasses “on statins”
Agreed Mike. Expanding outwards from the traditional target area has the effect of re-inforcing the base market in the non-discerning mind’s eye.
Thanks for the clarification Chris. The relevance of diarrhoea was testing my scant medical knowledge.
It appears that another family member of mine has been helped by stopping a drug. This time BP medication. Earlier in the year I wrote about my mother and her side effects from taking a statin. Now this time it is my father experiencing side effects likely caused by blood pressure medication.
At some point dad began to develop a lot of hacking, poor energy levels and to me seemed depressed. I suggested he take a vacation from his medications to see if they were the cause. As far as I can tell, the BP medicine appears to have been the cause, as once he stopped taking it to me he appeared healthier.
The answer still remains uncertain though. The health improvements seen did not happen right away, but instead over a week or so. Speculation has begun that maybe it was something the air at the time causing the issue. The cats have been under suspicion. And just possibly it was a long time problem that became much worse for some reason.
So to be sure of improved health, an appointment was made with a throat and ear specialist. As typically occurs in my family, once the appointment was made all symptoms have gone away. A cure has been found!
I’m reading the book Doctoring Data once again as I recall a great deal was written about BP medications. The opening part of the book about cancer screening reminded me of a neighbor. In all honesty I don’t know the story well. I was told it by another person. This is what I gathered. A stunningly beautiful neighbor had a typical breast screening done a few years ago. The results came back mixed. It might be cancer, it might not be cancer. To be sure though she decided to have her breasts removed. She then had preventive treatment done. I believe this is what happened. Well, I rarely see this woman. A few months ago though I ran into her and she had aged considerably. I’m guessing that occurred due to the cancer treatment. If I hadn’t known the cancer treatment given I’d think she had developed a drug habit, possibly a meth taker. On the positive I suppose she has caught up with and passed her husband’s age in appearance. (Not very nice to say I know.) I don’t know why I’m mentioning other than I recall at the time when i heard she was taking a radical direction with her treatment due to the screening, thinking in all likely hood she needed little if any treatment. We all have to make our decisions though that we feel are best.
Cough and lethargy are common adverse effects of some BP drugs.
Soul
Re blood pressure & part 58 from just over a year ago, extract as follows ;
“If you must take medication, I was a very strong supporter of ACE-inhibitors, in that they blocked angiotensin II, and increased NO synthesis. Both good things. However, some research has come out recently, suggesting they may increase the risk of lung cancer. Not by a great deal”
Thanks Sasha and Jerome. I remembered that quote from this sight! It’s a good one. It was in part what I referenced to help dad. So far my father has been doing much better since avoiding the BP medication. He hasn’t been coughing. He hasn’t complained about it, at least not to me. His energy level has improved also it appears. Overall, dad now seems to be back to his old self.
Personally I’m pretty sure it was the BP medication he was recently placed on that was causing the problems. Dad has some beet powder to raise NO levels if he wishes to try and lower his BP levels naturally. As far I know though he hasn’t tried it.
Now I’m going to have to worry about the EKG Apple watch dad recently bought. Dad enjoys his electronics. I hope this latest toy doesn’t have him running to the hospital mistakenly fearful a cardiac.
This study (1) says the “risk of stroke went up 33 percent with each blood pressure medicine” and “three or more blood pressure medications had a stroke risk of 2.5 times higher”. That’s a 250% increase! They go on to say: “You’re in as much trouble by the time you are on three medications that achieve excellent control as you are when you have hypertension and it is untreated, which is amazing,” Howard said. “We want to raise the issue that, despite great advances in a pharmaceutical approach, relying solely on this approach is going to come at a dear price of people’s lives.” This study (2) finds that ACE inhibitors are linked to increased lung cancer risk.
1.https://www.sciencedaily.com/releases/2015/05/150529193554.htm
2.https://www.bmj.com/content/363/bmj.k4471
Thanks Dr. John H for the study information. Last I checked with my father his BP levels were not all that high. They were borderline from official guidelines if I recall correctly. So from my stand point, good that he got off of them. Doubt they were doing much of any good, possibly causing harm, and as mentioned came with unpleasant side effects.
I forgot to bring the topic up today with dad. Tomorrow I’ll have to see how he is now doing, and what if anything he plans to do going forward with his BP.
The lead headline in todays paper is a tragic piece. A local guy 40 years of age died apparently of a heart attack. He had been at the hospital due to his wife giving birth to their 7th child.
Interesting factoid: some years ago I was going to run my lipids through the Iranian calculation (as by then I had low trigs) and was surprised to find my LDL did not correspond to the Friedwald equation but was closer to the Iranian calculation, from which I surmised that it was actually measured.
Sine then the doctors changed labs and later results were Friedwald calculated.
Currently to get a full lipid panel requires a doctor, the nurses are only permitted a cut-down version which gives TChol and a “ratio”. I’ve heard of a LOT of people who no longer get trigs reported, which is ridiculous as they have to be measured to calculate the LDL. I assume the reason is that they are testing for statin deficiency, not health. High trigs and the trigs/HDL ratio are strong markers for potential CVD. Obviously if people with high “non-HDL” have mostly high trigs, as I used to, then statins are a waste of time. Oh have I let the cat out of the bag?
JDPatten: Off-topic, but interesting. I’m reading Stephan Talty’s “The Illustrious Dead,” about Napoleon’s 1812 defeat by the Russians, the Russian winter, and especially by typhus. I didn’t think about the connection to you until he identified the bacterium by name; then I remembered. A horrifying disease.
He probably would have been more successful had he started his invasion 200 years later. It’s middle of December and it’s +2 celcius in Moscow.
Sasha: Moscow has been relocated to Tahiti? Book me a flight.
I’ve finally tracked down the source mentioned in my post of 11th December, about how the body can waste energy when in nutritional ketosis. It is not in something I read, but a lecture given by Dr Mike Eades shown on YouTube entitled “Does fat burn in the flame of carbohydrate?”. The relevant section is around 14 minutes in.
The gist seems to be: when the liver is making ketones from fatty acids, it produces a lot of high energy ATP for which it has no use. So it runs this through some horribly complex, biochemical pathway called the glycerol 3 phosphate shuttle and gradually expends it as heat.
It does seem to work. I still have limited stamina for any kind of exercise, though my repertoire of light housework is increasing as I lose weight, but, when in ketosis, I do not feel the cold as much as I used to, and in summer I have to watch I don’t overheat, even at 53 degrees north in Yorkshire!
https://gpnotebook.com/simplepage.cfm?ID=-2066743279&linkID=6595&cook=yes
I’ve posted a link to GP notebook’s bit on Wilson’s criteria of screening, as this study is effectively advocating screening the young for ‘pre heart disease’ , and I reckon that, apart from the fact that heart disease is important, this suggestion would break every other criterion, and yet it is being rubber stamped through.
I don’t think it’s in anyway an exaggeration to say that seeing a doctor is one of the most dangerous things you can do in this day and age
Statins and vaccines are just two of the most obvious examples of the widespread poisoning of the nation in the name of money. Nearly all of my elderly relatives are now on medications which have harmful side effects and do no discernible good of any kind – as for the flu shot, anyone administering that should be locked up (there’s no excuse, the evidence is there).
Perhaps when we redesign medical education to attract people interested in actually healing people rather than BMWs and golf club memberships we can start taking the first steps to having a health system that actually works for the people.
But that day’s a long way of…….great blog
Hi Dr. Kendrick,
I’m a big fan of Ivor Cummins and have been reading your blog for several months. As an Electrical Engineer, I understand the Pareto Principle and Root Cause Analysis and see little or none of it in the Pharmaceutical based medicine. Ivor talks to lots of smart people and I’ve been learning a lot from them.
In a recent interview with Dr Stephen Hussey, Dr. Giorgio Baroldi was mentioned as he conducted studies on hearts from cadavers and used a technique of injecting plastic into a heart and examining the arterial structure. He was doing this in the ’50’s. Apparently only a small number of heart attacks were attributed to blockages and many of the hearts with blockages had secondary bypass arteries formed around the clots. The people that did die of heart attacks had blockages in other areas of the heart but not in the area of the heart attack. Have you looked into Baroldi’s work?
The other thing, Hussey mentioned that Angina is simply Lactic Acid buildup caused by the heart burning glucose instead of fat. If the simple fact that someone with Angina just had to do a fast and switch to a Keto diet to reverse heart disease were advertised, think of all the suffering that could be allieviated.
I’m at the same age 57, that my Dad had his heart attack. I’ve successfully taken off 70lbs with LCHF/Keto diet with Intermittent Fasting. Hopefully, I won’t follow in his footsteps with heart disease and diabetes.
Kind Regards,
Kevin Frechette
Thanks for your comment. Angina is not simply a build up of lactic acid by the heart burning glucose instead of fat. Although, clearly, using fatty acids as an energy substrate would help. Angina is primarily caused by a narrowing of the coronary arteries. This reduces oxygen supply and switches the heart to anaerobic metabolism, thus causing build up of lactic acid. I agree that the thinking around the causal mechanism of infarctions needs a re-think.
Hi Kevin: re Pareto Principle and CVD
Another important Pareto factor: muscle/brain axis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117390/
Endocrine Crosstalk Between Skeletal Muscle and the Brain
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770965/
Physical Activity and Brain Health
“causal mechanism of infarctions needs a re-think.”
Sounds interesting!
And Merry Christmas and cheers to you with an “Ardbeg”
Göran
Magnesium supplementation significantly increased FMD (blood flow increases in artery) Seven RCTs with 306 participants. https://pubmed.ncbi.nlm.nih.gov/29709832/
Would be interesting to know the dosage etc,
This study talks about amounts. Key – The diets of almost 50% of U.S. adults do not meet the estimated average requirement of magnesium https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412491/
This should be interesting. For Christmas dinner I’ve been invited over to an asian American families small gathering. Should be fun. It’s very nice of them. I hope to make it but am not entirely sure I will be able to, as some health issues seem to be flaring and the next morning after Christmas I need to be up early, by 3:00 to drive out to the airport. I will see.
I mention as the daughter is a drug sales rep. She makes $300,000.00 plus a year. I know this as the father likes to brag about it, repeatedly. His son in law only makes $100,000 a year and in Chinese is described by the father in unflattering terms for not making more. Good money for selling popular drugs to hospitals and doctors. I can see why the father is proud of his daughter.
If i make it I’ll find myself needing to be more positive about the medical industry. Well, not a requirement but the last time I went to a similar event, I found conversations went smoother when I was more pro modern medicine and wanted to hear about the latest drugs. I’m wondering this time what the latest soon to be cure for cancer will be. Maybe heart disease will soon be a thing of the past due to a bright green shinny pill coming out. Apparently the last cure for cancer I was told about didn’t workout. That seems to be a common theme in medicine unfortunately. I’m glad lots of wine will be served.
Soul: Go, and enjoy, if only for the food. Homemade Chinese food is fabulous.
Peter Attia’s latest newsletter on measuring Cardiovascular disease risk with some good graphics:
https://peterattiamd.com/measuring-cardiovascular-disease-risk-and-the-importance-of-apob-part-1/
Some twitter response to the article here:
HI MadMax: appears that Peter assumes all apoB particles are identical, not according to this study from Jordan:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6178372/
Glycated LDL-C and glycated HDL-C in association with adiposity, blood and atherogenicity indices in metabolic syndrome patients with and without prediabetes
I read Peter Attias study. I found it difficult to understand. Could our good Doctor K give us his opinion?
In my opinion he remains trapped in the same LDL is bad paradigm. Simply fiddling about with esoteric measurement. Or to be crude. You can polish up a turd. It remains what it always was underneath a gleaming exterior.
Well that is an encouraging answer, because, modestly , that was my conclusion.
Incidentally turd polishing is a Bojo quotation.
Try the Singleton from Dufftown over Xmas
Verb sap
😂😂😂
Dr William Davis, the author of Wheat Belly and Undoctored recommends making Magnesium Water as a low cost highly absorbable form of Mg
https://blog.undoctored.com/magnesium-water-undoctored-style/
All you do is add 3 tbsp of Milk of Magnesia to a 2 litre bottle of carbonated water. Drink 2 cups spaced in 1/4 c doses daily for 360 mg of Magnesium.
The laxative Magnesium Hydroxide reacts with the dissolved CO2 to form Magnesium Hydrogen BiCarbonate that is very bioavailable and cheap to make too.
For Herpes cure please inbox me
Is “Dr Tony Okoro” vetted ?
Has he or she slipped on to this site with approval ? Gonna cure everything except bacon!
Thank you, Malcolm, for calling this what it is, and for cutting through this mountain of rubbish masquerading as research.
And the Excel trial supports everything you’ve said about conflicts of interest: ‘the four main investigators all declared conflicts of interest.’
Gregg Stone has received personal fees or held equity in 20 private medical companies … He’s also the course director for TCT, which makes money from exhibitors who include stent makers Abbott (Excel Sponsor), Boston Scientific and Medtronic. Similar story with Prof Pieter Kappetein, who worked for Medtronic …
‘By Newsnight’s count, around half of the investigators on the trial had declared personal fees from companies that made stents, and around a third of those on the taskforce writing the guidelines.
These relationships are all within the rules.’
Amen