Executive summary

I recently did a webinar on fibre with Dr Peter Brukner for the “Defeat Diabetes” organisation. I was asked 12 questions by Peter (before moving on to questions from the audience). This note contains a video of the webinar and a summary answer to each question. The questions were:

1) What is fibre?

2) We've been told for years – Denis Burkitt etc – that fibre is essential. Is there any evidence for that?

3) Fibre is supposed to prevent constipation, what's the evidence for that?

4) We hear that grains, especially whole grains are an essential part of a healthy diet. Tell us about whole grains and fibre.

5) As low carb eaters, we get criticised for not getting enough fibre. What's your response to that criticism?

6) What about fibre and its impact on blood sugar?

7) Can you have too much fibre?

8) If the evidence isn't there for fibre, how come they are in all the dietary guidelines?

9) Surely these guidelines are supposed to be based on scientific evidence.

10) How do we reverse these guidelines? Surely this can't continue.

11) Don't we need fibre for the gut microbiome?

12) If you had 30 seconds to tell the public the truth about fibre, what would you say?

Introduction

On 25th June 2025, I did a webinar with Dr Peter Brukner for the organisation that he founded, which is called “Defeat Diabetes” (Ref 1). Defeat Diabetes is an evidence-based program, led by doctors and dietitians, to improve blood glucose levels and management. We chatted about this organisation and Peter’s work in Australia when Peter came on my podcast (published December 2024) (Ref 2).

There were a number of topics that we could have tackled but Peter suggested that fibre would be popular. You can see the hour’s webinar at the end of this note.

I was asked 12 questions. This note gives you a succinct answer to each one. (The webinar answer is longer in most cases). Answers may differ to those on the webinar – sometimes better thoughts come as I write.

Introduction

Having refreshed the signpost articles on cholesterol and statins, it seemed timely to do a podcast with a heart patient who has done his own research and transformed his own health. Dr Tony Royle is a friend of ours and an excellent case study for patient advocacy. Andy and I first met Tony at the Public Health Collaboration conference in 2018. Tony and I both spoke at the 2022 Public Health Collaboration conference, which was in Bristol. We live quite near to each other and meet up regularly to ‘chew the fat’.

In this punchy hour we go through Tony’s background – from science to military flying to commercial flying, to never being able to fly again. What happens when you have a heart attack? What system do you get thrown into? How do you get out of it? Given Tony’s parallel academic career in science, we also got onto corruption in academia and medicine and the discouraging lack of curiosity in students today.

Bio

Dr Tony Royle, PhD, is a former military and civilian pilot who has enjoyed a parallel academic career studying and teaching various aspects of science, engineering and mathematics. These days his focus is on helping people understand the potential causes of diseases such as type 2 diabetes, atherosclerosis, and obesity, whilst suggesting natural strategies to reverse or manage them.

His move into the realm of health and fitness was prompted by an unexpected heart attack in 2014 that cut short his flying career with Virgin Atlantic but opened doors to some startling revelations about the nature of the allopathic medical system and the fundamentally flawed national nutritional guidelines, particularly the fallacies they promoted concerning cholesterol and saturated fats. He looks at health through the lens of an engineer rather than a clinician and is a strong critic of mainstream medical and nutritional research and dogma – forces that he feels are often used in conjunction with the media to manipulate people’s perceptions, beliefs, and actions.

Tony’s strategy to turn his own health around was to combine a ketogenic diet with various modes of fasting and exercise, a regime that enabled him to go from heart attack to Ironman triathlete in under three years and one that involved no allopathic drugs.

Questions & approximate time stamps

01.45 How did you get into engineering, physics, chemistry, maths, and all that clever scientific stuff?

03.45 What's your PhD in?

05.20 How long were you a military pilot and did you see service?

06.18 Then you became a commercial pilot. Did you work for Virgin all the time or did you work for a few airlines?

07:04 Did you have any hairy moments while you were there?

07.45 On 9-11 where were you?

08.45 What happened Christmas 2014?

10:05 Did you feel unhealthy beforehand? Were you living an unhealthy life?

11.15 How does it feel to have a heart attack? Did you know? Did you walk into A&E? What happened?

12:45 What system kicks in when you’re had a heart attack?

14.50 What drugs were you put on? How quickly did you start to feel unwell?

17.10 You started researching. Where did you start? How did you go about it? What did you find?

18.35 You didn't stop there, did you? You didn’t just stop drugs. You've gone further and further down looking after your health…

20.45 What were your before and after measures (health markers)?

22:40 You still fast quite regularly now, don't you?

23:10 Sell me the benefits of fasting.

25.40 When you've lost 50 pounds and your resting heart rate is 43 and all the rest of it, you go back to your medics who wanted to give you a quadruple bypass. And of course, they give you a gold star and say, Dr. Royle that is just magnificent. We're now going to do that with all our patients. Is that what happened?

26.00 So what did happen and do you still see them [your medics] or did you manage to get out of the system?

28:00 How many Ironmen have you done and marathons and half marathons and all the other stuff?

32:25 Do you do your exercise fuelled on fat or do you do it fasted? What works best for you?

34.40 Have you seen that this is where Tim Noakes has got to with his work with Philip Prins, that they think that kind of exercise intensity, you probably need to be getting in about 10 grams of carb an hour. And they think it's not to protect the glycogen, they think it's to avoid hypoglycemia...

36.30 You've not been ill, but you've had a few injuries – tell us about those.

37.40 Does doing what you do help repair injury as well as avoid illness?

38.45 When you realized that statins are a con and the whole great cholesterol con, do you think this is going on in other areas? And in which case, which are the big ones do you think where we've got some other con going on in medicine and healthcare?

44.10 So then turn it the other way around. Is there anything in what you call allopathic medicine that you think is valuable? Any drug, any intervention?

46.30 Having been in education for at least 10 years, what do you think of students? Are they getting more curious, less curious? Are you encouraged, discouraged?

49.35 How do you get people to open their minds?

59.00 Have we missed anything?

Thoughts for the day

Two of my favourite passages were these:

At approximately 46 minutes, Tony and I were talking about healthcare when he said: “We need to stop the demand on the system, which we can do. I have not been a demand on the system since I fell off my bike. If everybody was like me, there would be no queues at the doctors. You could get an appointment in the morning, could turn up hospital and be treated straight away. That's the solution. But the system doesn't want a solution because it makes money out of its way of dealing with things. It wants to sell you drugs. It wants the doctors to prescribe them because it's all driven by profit and not by people's health. Simple as that.”

At approximately 55 and a half minutes, we were talking about education, open mindedness and barriers to healthy living. Tony observed: “But people don't even know they're in a box. This is the real problem. They think they're open minded, but they don't realize that open mind is actually contained within a box. They can think open-mindedly within the constraints of a box that they don't even know is there. And there's also this ridiculous notion of authority where society seems to think that other human beings can have some major influence on other human beings. We're all equal, we're all born equal, and we should all live equally. And if we did that, we'd all be living in abundance. We would all have more than enough time, food, energy, everything that you care to name, we would have plenty of it – if what's available was evenly distributed amongst us. But it's not. It's hoarded by a tiny percentage of individuals and entities on this planet. And because of that, the average person struggles.”

Tony hopes that his story and experience may help others to take charge of their own health and to realise that health can improve after a major event – all is definitely not lost.

Here is the video of the discussion

Executive summary

* One of the most common questions I am asked is how do I stop my doctor pressuring me into taking statins? This note provides information (not advice) on this topic with the following sub-headings:

1) Voluntary & Informed consent. How is this defined? How can the principle of voluntary consent alone be used to stop pressure from medical staff, friends or family? What does the principle of informed consent mean and where does the onus lie?

2) The cholesterol test. Your numbers will be presented to you confidently and categorically. Should they be?

3) The Number Needed to Treat and to Harm. What is the Number Needed to Treat and the Number Needed to Harm for statins for your risk profile?

4) The life extension analysis. If you take statins for five years, how much longer might you expect to live?

5) The patient leaflet. What does this tell us about side effects? What does this tell us about warnings and precautions?

6) How benefit & harm are presented. What's relative risk? What's absolute risk? How will the benefits of statins be presented to you and what does this mean?

7) The risk assessment. What are the biggest risk factors for heart disease? Where does cholesterol fit in? At what age will risk calculators decide you need to take statins, even if your health is optimal?

8) The mechanism. What do statins actually do?

Introduction

The two most common questions I am asked are 1) how do I lose weight? And 2) how do I stop my doctor pressuring me into taking statins? The answer to (1) is in this post from 2021 (Ref 1). The answer to (2) is in this post.

Statins are the medication that people seem most likely to be pressured into taking. Doctors often offer anti-depressants, for example, but they seem OK to have them refused. There is pressure to take blood pressure meds, but nothing compares to the pressure that people tell me they get when a medic has decided that their cholesterol is ‘high.’ The signpost note as to why you shouldn’t worry about cholesterol is here (Ref 2). That note also covers what high cholesterol actually is (because it’s not 5 mmol/L (193 mg/dL)).

This note presents information that may be helpful if you are under pressure to take statins. The first point will help with any medical or family coercion. The first point is, in fact, the only point needed in this note. However, I’ve presented more for completeness and to summarise what you should be told.

This is not advice. This is information. What you do about your health is up to you – and that’s the point of this note. It should be up to you, but too many people don’t seem to realise this when it comes to statins. The most recent query that I received on this topic shared “I am being bullied by my doctor to take statins. I said no thank you. My doctor called in a prescription to my pharmacy!” That is completely against the first principle of healthcare, so let’s start there.

Introduction

During the recent update of our zoeharcombe.com web site we reviewed the hundreds of articles to assign them the best category and tag matches for optimal searching. I also chose my favourite articles for the nine ‘super categories’ that we created. One of the super categories is “Cholesterol & Statins.” This is probably the top super category. Whenever I do an article on this topic, I receive more comments and replies than on any other subject.

One of the most important posts in the Cholesterol & Statins category was written over 10 years ago. It was called “Worried about cholesterol and/or statins” (Ref 1). It’s time for this to be updated. This topic and the number of posts that I’ve written on it have grown so much that this is the first of two notes. This one is “Worried about cholesterol?” and next week’s will be how to deal with “Pressure to take statins.”

This is a signpost article that will refer you to other articles, which go into greater detail about that point. It covers the following:

- Some basics about cholesterol.

- Conversions between mmol/L and mg/dL.

- Cholesterol targets in the UK & US.

- Do you have high cholesterol?

- What if your cholesterol is above 10 mmol/L (387 mg/dL)?

- Is the cholesterol test accurate?

- Why cholesterol can’t cause heart disease (covering saturated fat and cholesterol, saturated fat and heart disease and cholesterol and heart disease).

- Cardiovascular disease (CVD) calculators and cholesterol as a risk factor.

Some basics about cholesterol

1) It is virtually impossible to explain how vital cholesterol is to the human body. If you had no cholesterol in your body you would be dead. No cells, no bone structure, no muscles, no hormones, no sex, no reproductive system, no digestion, no brain function, no memory, no nerve endings, no movement, no human life – nothing without cholesterol. It is utterly vital and we die instantly without it.

2) Cholesterol is so vital that our bodies make it. The body cannot risk leaving it to chance that we would get it from food or some other external factor – that’s how critical it is.

3) There is no such thing as good cholesterol and bad cholesterol. Cholesterol is cholesterol. The chemical formula for cholesterol is C27H46O. There is no good version or bad version of this formula. HDL is not even cholesterol, let alone good. LDL is not even cholesterol, let alone bad. HDL stands for High Density Lipoprotein. LDL stands for Low Density Lipoprotein. (The main three other lipoproteins are chylomicrons, Very Low Density Lipoproteins (VLDL) and Intermediate Density Lipoproteins (IDL)).

Fat and cholesterol are not water soluble and so they need to be carried around the body in something to do their vital work. The carriers of such substances are called lipoproteins. We can think of lipoproteins as tiny ‘taxi cabs’ travelling round the blood stream acting as transporters. So, lipoproteins are carriers of cholesterol – oh – and triglyceride and phospholipids and protein. All lipoproteins carry all of these substances – just in different proportions. LDL would more accurately be called the carrier of fresh cholesterol and HDL would more accurately be called the carrier of recycled cholesterol.

Conversions between mmol/L and mg/dL

The UK, Australia and most of Europe report cholesterol in mmol/L. The US uses mg/dL. Here’s a conversion table for convenience (rounded to the nearest whole number). This table works for total cholesterol, LDL-Cholesterol (LDL-C) and HDL-Cholesterol (HDL-C). There is a different conversion for triglycerides.

Cholesterol targets in the UK & US

The UK targets are for total cholesterol to be below 5 mmol/L (Ref 2).

If you want something really unscientific, check out the UK advice for cholesterol. We should aim for 5-4-3-2-1 apparently (Ref 3). This translates to: total cholesterol below 5 mmol/L; the ratio of total to HDL-C below 4; LDL-C below 3 mmol/L; triglycerides below 2 mmol/L; and HDL-C above 1.0 mmol/L (Ref 4).

Converting these numbers to mg/dL gives the following (rounded to the nearest whole number) (Ref 5).

You know that something can’t be scientific when 5-4-3-2-1 in the UK would translate to 193-4-116-177-39 in the US.

The US considers total cholesterol above 200 mg/dL to be high (Ref 6). Optimal is set at “about 150 mg/dL” (which is below 4 mmol/L). The US CDC (Centers for Disease Control) page references a paper, which sets out even lower targets for people at different risk levels (Ref 7).

Do you have high cholesterol?

Many queries that I receive start with someone saying that they have high cholesterol. But do they? They probably do relative to the redefined normal, but is this really high cholesterol?

I wrote this post back in 2014 (Ref 8). It showed how normal had been redefined for diabetes, cholesterol and blood pressure. If normal can be redefined, more people become eligible for treatment. ‘Normal’ then becomes progressively more distorted because drugs continue to lower the true population norm.

In that 2014 post, I posted an academic paper to the web archive to preserve it (Ref 9). It proved difficult to find the true population norm before years of cholesterol lowering treatment had lowered it further. Even this normal distribution was from 2008. Lovastatin was given FDA approval in 1987 making it the first commercial statin (Ref 10). Hence statins had been lowering population cholesterol for 20 years before this normal distribution was captured.

The following chart comes from that web archived paper. The paper was called “Measurement of baseline total cholesterol: new data from The Health Improvement Network (THIN) database” (Ref 11). THIN stands for “The Health Improvement Network.” HSE stands for “The Health Survey for England.” THIN is a database of anonymous medical records collected at GP (family doctor) surgeries around the UK. At the time of the 2008 paper analysis, THIN included 326 practices with a total of 5.5 million patients.

The diagram below indicates that the total average (mean) cholesterol recorded on THIN was around 6.5 mmol/L. The paper confirmed that this number was 6.57 mmol/L. By defining 5 mmol/L as high, everyone to the right of 5 (most people) can be told that they have high cholesterol and this is then a target for treatment. It’s a brilliant marketing strategy to increase sales of your drug with the stroke of a pen.

In reality, everyone on a normal distribution is – by definition – normal. The people with total cholesterol of 2 mmol/L are normal. The people with total cholesterol of 10 mmol/L are normal. If you’re on that chart, you’re normal – end of. That’s 77 – 387 mg/dL – all normal.

What if your cholesterol is above 10 mmol/L?

If your total cholesterol is above 10 mmol/L (387 mg/dL), there could be a number of explanations:

1) You could have Familial Hypercholesterolemia (FH). FH is a genetic condition caused by a gene defect on chromosome 19. The defect impairs the body’s ability to remove low density lipoproteins (LDL) from the blood stream, resulting in consistently high levels of LDL. Please note that this is very unlikely. There are two types of FH: Heterozygous FH is found in 1 in 500 people; Homozygous FH is much rarer, occurring in 1 in a million births (Ref 12).

The two main posts on Familial Hypercholesterolemia are here (Ref 13). The 2016 post may give you a different perspective on FH. High LDL (and I mean LDL, not LDL-C) might be the symptom, not the problem. The problem might be the exact opposite of what is assumed – that LDL is not getting to the cells (including heart cells) where it is vitally needed. If you genuinely suspect that you have FH, I recommend getting a genetic test to confirm the gene defect on chromosome 19. Doctors are increasingly telling people they have FH whenever they see a ‘high’ cholesterol reading. Most people won’t have FH. The rarity of FH guarantees this.

2) If you are on a ketogenic diet and you are lean (BMI around 22) and your cholesterol has risen dramatically since starting a keto diet, you may be what has been termed a Lean Mass Hyper Responder. My posts on this are here (Ref 14).

3) Your cholesterol test may be inaccurate – see below.

4) Your cholesterol level may be high for you right now – for a reason. Your body makes cholesterol for good reason – does it need more right now? Are you injured? stressed? pregnant? recovering from an operation? illness? Any of these will encourage your body to make more cholesterol.

Have you had a cholesterol test taken at the end of winter? in the heart of winter? Vitamin D is made by sunlight synthesizing cholesterol on the skin when you expose your skin to sunlight. Your cholesterol may simply be ‘high’ right now because you haven’t turned it into vitamin D (it’s the low vitamin D that will harm you – not the ‘high’ cholesterol – the high cholesterol can be a sign that you’re lacking vitamin D). Have another test at the end of the summer and make sure you give your body the chance to make some vitamin D with healthy sun exposure (not too much, not burning).

Is the cholesterol test accurate?

In a word, no. My main post on this was written in December 2024 (Ref 15). Here are two headlines – there is a wealth of information in the full post if this topic interests you:

1) The standard blood cholesterol test does not measure LDL – it estimates it. The fasting blood cholesterol test can only measure total cholesterol and HDL. There are two other unknowns in a four-variable equation – LDL and VLDL. The estimation is refined further using the Friedewald equation (named after William Friedewald, who developed it).

The mmol/L formula for blood cholesterol levels is:

Total cholesterol in mmol/L = LDL-C + HDL-C + triglycerides/2.2

i.e., in countries that use mmol/L, the total cholesterol number in your blood test is made up of the cholesterol in the LDL taxi (LDL-C) plus the cholesterol in the HDL taxi (HDL-C) plus the triglycerides divided by 2.2.

The mg/dL formula for blood cholesterol levels is:

Total cholesterol in mg/dL = LDL-C + HDL-C + triglycerides/5

i.e., in countries that use mg/dL, the total cholesterol number in your blood test is made up of the cholesterol in the LDL taxi (LDL-C) plus the cholesterol in the HDL taxi (HDL-C) plus the triglycerides divided by 5.

2) My favourite paper (letter to the BMJ in fact) on cholesterol test inaccuracy is by Fraser & Fogarty (Ref 16). If a doctor sees a patient whose cholesterol has changed since the last visit, the doctor wants to know if that change was significant or if it could have been caused by analytical and biological variation.

Fraser & Fogarty reported, “When measuring cholesterol concentration, a difference of 19% is required for a significant (p<0.05) change since the ideal coefficient of analytical variation is taken as ≤3% and the average within subject variation is 6%.” I.e., if changes are below 19%, this cannot be considered meaningful. E.g., if someone’s first reading was 6 mmol/L, the second reading would need to be below 4.86 mmol/L or above 7.14 mmol/L to be seen as a relevant change. Few people know that.

Why cholesterol can’t cause heart disease

The black swan theory goes as follows. If your hypothesis is that all swans are white and you see one black swan, your hypothesis has failed. You need to develop another hypothesis because one anomaly has defeated it.

The diet-heart hypothesis has mutated over the years, but – at its essence – it claims that (saturated) fat raises cholesterol and cholesterol causes heart disease. Variously, it flits between total dietary fat and saturated fat and total cholesterol or LDL-Cholesterol or the ratio of one cholesterol to another. When something doesn’t work, it mutates. There are so many black swans in this hypothesis that it should have died long ago, but it prevails. Here are some black swans for you…

Saturated fat and cholesterol

1) (Not so) common sense.

Some will say, yes I know the body makes cholesterol and there shouldn’t be a design flaw but if we eat too much fat – saturated fat especially – then the body will make too much cholesterol and it will clog up our arteries and we will die. (Insert the rolling eyes icon).

i) Sucrose (table sugar) is the only food I have yet found that doesn’t contain even a trace of saturated fat. Even salads, vegetables and fruits contain tiny amounts of fat and thus trace amounts of saturated fat, given that all foods that contain fat contain all three fats (saturated, monounsaturated and polyunsaturated). To believe that saturated fat is harmful in any way is to believe that God and/or Mother Nature are ‘out to get us.’

ii) All fat and saturated fat is consumed. It is not injected into arteries (unless someone is being fed in hospital in an emergency situation). Those who claim that saturated fat will raise cholesterol need to demonstrate how and why. (Please note, I know how increasing polyunsaturated fat can lower cholesterol – through the plant sterol mechanism. Hence someone might reduce saturated fat and increase polyunsaturated fat but the higher polyunsaturated fat lowered cholesterol, the lower saturated fat didn’t (Ref 17)).

iii) Even if saturated fat did raise cholesterol, you still don’t have cholesterol in your blood stream and hence there is nothing in your blood stream clogging up your arteries. You have lipoproteins in your blood stream carrying cholesterol – and protein and phospholipids and triglycerides. The minute someone starts talking about LDL, they are no longer arguing about cholesterol, they are presenting a lipoprotein theory of heart disease (Ref 18). They’re perfectly entitled to do that but they are not entitled to jump between LDL and LDL-C as if there is no difference.

2) Saturated fat does not impact cholesterol levels.

Dr. Ancel Keys, the same man who did the brilliant Minnesota starvation experiment, spent the 1950’s trying to show that cholesterol in food was associated with cholesterol in the blood. He concluded unequivocally that there was not even an association, let alone a causation. He never deviated from this view.

The most definitive statement made by Keys on this subject was recorded in a 1954 Symposium on Atherosclerosis: "The evidence – both from experiments and from field surveys – indicates that cholesterol content, per se, of all natural diets has no significant effect on either the cholesterol level or the development of atherosclerosis in man" (p.182 – original emphasis) (Ref 19).

When no relationship between cholesterol intake and cholesterol levels could be found, Keys hypothesised that dietary fat could be associated with cholesterol levels. This premise had a logical flaw. The only foods that contain cholesterol are animal foods: meat; fish; eggs and dairy products. Keys was aware of this: “Cholesterol occurs only in foods of animal origin” (Ref 20). This was reinforced in the 1952 publication, The Cholesterol Problem: "cholesterol is not contained in plants or plant products but it is present in all animal tissues” (Ref 21).

All foods that contain cholesterol contain dietary fat. They all contain all three types of dietary fat: saturated; monounsaturated and polyunsaturated. Only the proportions of each fat vary (Ref 22). To increase the dietary cholesterol in his human subjects, Keys needed to feed them foods of animal origin. This had no impact on blood cholesterol levels, or the development of atherosclerosis in man (Ref 23). Animal foods, per se, had been simultaneously exonerated. Saturated fat, per se, had been simultaneously exonerated (Ref 24). Not many people know that.

3) The food with the highest saturated fat content does not raise LDL-Cholesterol.

In 2018, a randomised controlled trial aimed to assess the change in LDL-Cholesterol (LDL-C) arising from consumption of coconut oil, butter and olive oil. Coconut oil and butter contain mostly saturated fat; olive oil contains mostly monounsaturated fat (all foods with fat contain all three fats). Coconut oil is the substance with the highest saturated fat content of any food at 83% (Ref 25). LDL-C increased with butter, while there was no difference between coconut and olive oil (Ref 26). This negated the hypothesis that saturated fat raises cholesterol.

Saturated fat and heart disease

1) Saturated fat & CHD are inversely related.

This post presented data for 44 countries in Europe – matching saturated fat as a percentage of energy in the national diet and death rate from coronary heart disease (CHD) per 100,000 people for men and women (Ref 27). The relationship was inverse for both men and women i.e., higher saturated fat was associated with lower death rates.

In his brilliant book, “The Great Cholesterol Con”, Dr Malcolm Kendrick reviewed the top and bottom seven countries for saturated fat intake in Europe and the countries with the highest and lowest levels of heart deaths. He used the MONICA data from c. 1998. I repeated this for the 2008 data (Ref 28). It showed that:

- Death rates for men were 3 times higher in the lowest saturated fat intake countries than the highest.

- Death rates for women were 4.5 times higher in the lowest saturated fat intake countries than the highest.

2) North Karelia, Finland.

Some people – who think they know their stuff – will say ‘Ah but Finland showed that reducing (saturated) fat reduces heart disease.’ They cite the case of North Karelia, which was one of the two Finland cohorts in the classic Ancel Keys’ Seven Countries Study.

A number of health interventions were started in North Karelia in 1972. The three major factors being addressed were blood cholesterol, blood pressure and smoking. It was assumed that dietary change would impact blood cholesterol levels.

The Finland/North Karelia literature claimed that reduced intake of saturated fat led to an 80% reduction in annual cardiovascular disease (CVD) mortality rates among the working aged population. It cannot be assumed that (saturated) fat reduction made the difference to heart disease. Smoking among men more than halved, which is likely to have made the biggest difference.

There was another significant factor, which was overlooked by the article published about North Karelia. The Seven Countries Study comprised men aged 40-59 in 1956. These men were aged 29-48 in 1945, when World War II ended, and they were between 23-42 years old when World War II began. North Karelia was ravaged during World War II and virtually the entire population of Karelia was displaced. War and displacement would have caused high heart and all-cause mortality. Since people can’t die twice, deaths would have fallen following this traumatic period whether butter or margarine was put on bread. The full Finland rebuttal is in this post (Ref 29).

Cholesterol and heart disease

We’ve undermined the first part of the diet-heart relationship – that saturated fat raises cholesterol and/or saturated fat causes heart disease. Even if saturated fat did raise cholesterol, there are enough black swans to negate the hypothesis that cholesterol causes heart disease:

1) Data for 192 countries in the world.

In 2010, I first looked at the relationship between average (mean) cholesterol levels for countries and deaths from cardiovascular disease (CVD) and all-causes. I found all relationships to be inverse. For men and women, for CVD deaths and all deaths, the higher the cholesterol level, the lower the death rates (Ref 30).

This research was published in a peer reviewed journal article in 2020 (Ref 31).

2) Women.

Using Europe data again, the European cardiovascular Disease (CVD) Statistics document provided information on cholesterol levels and disease incidence by gender (Ref 32). P155 reported that “In Central and Eastern European and in Western Asian countries, raised blood cholesterol tended to be more common in females than in males.” To compare these higher cholesterol levels with heart disease, p12 reported “for both sexes in the EU, the age-standardised death rate for IHD in the latest available year is lowest in France (77 deaths per 100,000 in males; 32 deaths per 100,000 in females) and highest in Lithuania (700 deaths per 100,000 in males; 429 deaths per 100,000 in females).”

Women have higher cholesterol and lower deaths from heart disease. That’s the gender paradox.

3) Older people.

I presented the age black swan in this post, why cholesterol can’t cause heart disease, from February 2019 (Ref 33). The post followed the Statins in the over 75s (Lancet paper) Monday note from the previous week (Ref 34). It used the Appendix to the Lancet paper, which contained an interesting table (Webtable 3). The table was called "Mean plasma lipid concentrations at baseline and mean difference in plasma lipid concentrations at 1 year in participants in all studies, by category of age.”

The table showed that total cholesterol falls steadily from the youngest to the oldest age groups and LDL-Cholesterol falls steadily from the youngest to the oldest age groups. CVD incidents and deaths increase with age while cholesterol falls. That’s the age paradox.

Two more black swans were included in the post, why cholesterol can’t cause heart disease: the French and the Japanese (Ref 35).

4) Most heart events occur in people who do not have higher cholesterol.

One of the starred papers among the 1,500 articles in my EndNote is a classic study from 2009 (Ref 36). I refer to it as the ‘get with the guidelines’ study. This simple, but clever study reviewed the cholesterol levels of people arriving at hospital with coronary artery disease. Of 231,986 hospitalizations from 541 hospitals, admission cholesterol levels were documented in 136,905 people (59.0%). The study found that “In a large cohort of patients hospitalized with CAD, almost half have admission LDL <100 mg/dL, whereas less than a quarter have LDL >130 mg/dL.” i.e., most had lower cholesterol. The researchers’ conclusion was that we need “even lower LDL goals.” (Insert rolling eyes icon again).

This was reiterated in a recent Monday note – the one about the Polypill (Ref 37). One of the FAQs on the polypill site was: “My blood pressure and cholesterol are not raised. Will I still benefit from taking the polypill?” The answer was “Yes, you will benefit. Most heart attacks and strokes occur in people who do not have raised values” (Ref 38).

And finally – cholesterol and risk calculators

The Framingham Heart Study (FHS) brought us the first CVD risk calculator in 1976 (Ref 39). Kannel et al used the data gathered over 18 years on risk factors and incidence of CVD to establish a risk calculator, which could estimate the risk of a man or woman developing CVD in the next 8 years. The greatest determinants of CVD by a margin are age and sex. The 1976 article provided evidence for these being overriding risk factors for CVD. Per 1,000 people, 18 men and 5 women, aged 35, would probably develop CVD within 8 years; compared with 229 men and 199 women aged 70. CVD incident rates were 13 times higher for men and 40 times higher for women in the older age group.

In this first calculator, after age and sex, the strongest risk factors for developing CVD were glucose intolerance (correlation coefficient 0.6) and smoking (0.56) for men and glucose intolerance (0.68) for women (Ref 40). Smoking was not a major risk factor for women. Total cholesterol had a very small coefficient: 0.026 for men and 0.016 for women (Kannel et al ref). Interestingly, cholesterol in the FHS was taken as the measurement at the age of 45. Framingham found cholesterol to be even less important as a risk factor as people aged beyond 45.

The primary tool used in the UK is QRISK. The primary web site for QRISK is here (Ref 41). The current version is QRISK-3 (2018). The seminal (2007) paper is here (Ref 42). The objective of QRISK was to derive a new cardiovascular disease risk score for the UK and to validate its performance against the established Framingham calculator and a newly (at that time) developed Scottish score (ASSIGN). The 2007 paper concluded that QRISK performed far better for predicted CVD risk in the UK population than either Framingham or ASSIGN and so it is now the standard UK tool.

QRISK confirmed the now standard observations – age and sex matter more than anything else. In QRISK, the single cholesterol marker (the ratio of total cholesterol to HDL-Cholesterol) tested was found to have no impact whatsoever. It served no purpose as a risk factor.

QRISK2 arrived soon after QRISK1. It added ethnicity, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis into the risk factor pot. In QRISK2, the total/HDL cholesterol ratio moved off the line of no effect but it was inconsequential relative to other risk factors.

In QRISK3, cholesterol remained one of the poorest measures of CVD risk. The big issues were smoking, diabetes, and some auto-immune conditions that had been added e.g., Lupus.

From Framingham (US) to QRISK3 (UK), cholesterol has never been an important risk factor in CVD calculators (Ref 43). And yet, the most likely outcome from a CVD 10-year risk score of 10% in the UK and as low as 5-7.5% in the US will be a statin prescription. The CVD calculator score should drive glucose management and smoking cessation instead.

In summary

Cholesterol is utterly life vital. It is so life vital that our bodies are making it right now. I worry about a number of things, but I don’t worry that my body is trying to kill me.

Everyone on a normal distribution is – by definition – normal. The people with total cholesterol of 2 mmol/L are normal. The people with total cholesterol of 10 mmol/L are normal. If you’re on the normal distribution, you’re normal – end of. That’s 77 – 387 mg/dL – all normal. Normal means don’t worry.

You probably don’t have Familial Hypercholesterolemia (FH). The rarity of FH (1 in 500 or 1 in 1,000,000) guarantees this. You might be told that you have FH by doctors who think any cholesterol level above 5 mmol/L (193 mg/dL) is high. You might be a Lean Mass Hyper Responder. You might be stressed or lacking vitamin D. Your cholesterol test isn’t accurate anyway, so don’t worry about it.

Saturated fat is in all foods except sucrose. God/Nature really didn't put something in every food to kill you. Saturated fat doesn't impact cholesterol levels anyway and, across European countries, saturated fat and heart deaths are inversely related. So don't worry about saturated fat intake (unless it's low).

Across world counties cholesterol and heart deaths and all deaths are inversely related. So don't worry about cholesterol (unless it's low).

Even the risk calculators don't rate cholesterol as a predictive factor. They know that the biggest determinants of heart disease are age and sex. Don't get older and don't be male. That's two things you can’t do anything about, so don’t worry about them. Don't smoke and don't have high blood glucose levels – those are worth worrying about.

Worry can cause heart disease, so please don’t worry – especially don’t worry about cholesterol.

Ref 1: https://www.zoeharcombe.com/2015/03/worried-about-cholesterol-andor-statins/
Ref 2: https://www.nhs.uk/conditions/high-cholesterol/cholesterol-levels/
Ref 3: https://www.nhsinform.scot/illnesses-and-conditions/cardiovascular-disease/risk-factors-for-cardiovascular-disease/high-cholesterol/
Ref 4: Svilaas et al. Application of simple lipid treatment goals in patients with atherosclerotic disease. Nutr Metab Cardiovasc Dis. 2000. https://pubmed.ncbi.nlm.nih.gov/10919171/
Ref 5: The conversion for total, LDL and HDL cholesterol from mmol/L to mg/dL is to multiply by 38.67. The conversion for triglycerides from mmol/L to mg/dL is to multiply by 88.57. https://www.omnicalculator.com/health/cholesterol-units
Ref 6: https://www.cdc.gov/cholesterol/about/index.html
Ref 7: Grundy et al. AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018. https://www.ahajournals.org/doi/10.1161/CIR.0000000000000625
Ref 8: https://www.zoeharcombe.com/2014/06/diabetes-cholesterol-bp-normal-is-no-longer-normal/
Ref 9: https://tinyurl.com/2s4nj7ws
Ref 10: Endo. A historical perspective on the discovery of statins. Proc Jpn Acad Ser B Phys Biol Sci. 2010https://pmc.ncbi.nlm.nih.gov/articles/PMC3108295/
Ref 11: Thompson et al. Measurement of baseline total cholesterol: New data from The Health Improvement Network (THIN) database. Primary Care Cardiovascular Journal (pccj) 2008.
Ref 12: Mangiapane EH, Salter AM. Diet, Lipoproteins, and Coronary Heart Disease: A Biochemical Perspective: Nottingham University Press 1999.
Ref 13: https://www.zoeharcombe.com/2016/11/familial-hypercholesterolemia-fh/
https://www.zoeharcombe.com/2020/02/the-british-heart-foundation-and-familial-hypercholesterolemia/
Ref 14: https://www.zoeharcombe.com/tag/lmhrs/
Ref 15: https://www.zoeharcombe.com/2024/12/how-accurate-is-your-cholesterol-test/
Ref 16: Fraser & Fogarty. Interpreting laboratory results. BMJ. June 1989. http://www.bmj.com/content/298/6689/1659
Ref 17: Harcombe Z, Baker J. Plant Sterols lower cholesterol, but increase risk for Coronary Heart Disease. Online J. Biol. Sci. 2014.
Ref 18: https://www.zoeharcombe.com/2021/06/rebutting-the-cholesterol-hypothesis/
Ref 19: Keys, A., and Anderson, J. T. The relationship of the diet to the development of atherosclerosis in man. In: D. o. M. S. National Research Council, (ed.) Symposium on atherosclerosis. Washington, pp. 181-196. 1954.
Ref 20: Keys, A., Mickelsen, O., Miller, E. v. O., and Chapman, C. B. (1950c) The Relation in Man between Cholesterol Levels in the Diet and in the Blood. Science. Vol.112(2899), pp.79-81 (p.79 specifically).
Ref 21: Keys, A. (1952a) The cholesterol problem. Voeding. Vol.13 pp.539-555 (p.542 specifically).
Ref 22: Harcombe, Z., Baker, J., and Davies, B. (2013) Food for Thought: Have We Been Giving the Wrong Dietary Advice? Food and Nutrition Sciences. Vol.4(3), pp.240-244.
Ref 23: Keys, A., and Anderson, J. T. The relationship of the diet to the development of atherosclerosis in man. In: D. o. M. S. National Research Council, (ed.) Symposium on atherosclerosis. Washington, pp. 181-196. 1954.
Ref 24: P.S. The macronutrient that is largely absent from the foods that contain cholesterol is carbohydrate. Meat and fish have no carbohydrate content (with liver, offal, being an exception for any glycogen stored by the animal at the time of death). Eggs have a trace of carbohydrate. Dairy products approximate to five per cent carbohydrate content. Animal foods are either entirely, or in the main, water, protein and fat. (“Food for Thought” paper above).
The logical macronutrient for Keys to have studied was therefore carbohydrate, but attention was turned to fat.
Ref 25: https://fdc.nal.usda.gov/food-details/330458/nutrients
Ref 26: https://www.zoeharcombe.com/2020/04/coconut-oil-olive-oil-butter-ldl-cholesterol/
Ref 27: https://www.zoeharcombe.com/2015/03/saturated-fat-chd-in-europe/
Ref 28: Allender S, Scarborough P, Peto V, Rayner M. European Cardiovascular Disease Statistics: British Heart Foundation Health Promotion Research Group, 2008.
Ref 29: https://www.zoeharcombe.com/2023/05/did-finland-prove-that-reducing-saturated-fat-reduces-heart-disease/
Ref 30: https://www.zoeharcombe.com/2010/11/cholesterol-heart-disease-there-is-a-relationship-but-its-not-what-you-think/
Ref 31: https://www.zoeharcombe.com/2021/06/cholesterol-mortality-world-graphs/
Ravnskov et al. The LDL Paradox: Higher LDL-Cholesterol is Associated with Greater Longevity. Annals of Epidemiology & Public Health 2020. https://meddocsonline.org/annals-of-epidemiology-and-public-health/the-LDL-paradox-higher-LDL-cholesterol-is-associated-with-greater-longevity.pdf
Ref 32: Wilkins et al. European Cardiovascular Disease Statistics 2017. European Heart Network, Brussels. 2017. https://ehnheart.org/wp-content/uploads/2023/07/CVD-Statistics.pdf
Ref 33: https://www.zoeharcombe.com/2019/02/why-cholesterol-cant-cause-heart-disease/
Ref 34: https://www.zoeharcombe.com/2019/02/statins-in-the-over-75s/
Ref 35: https://www.zoeharcombe.com/2019/02/why-cholesterol-cant-cause-heart-disease/
Ref 36: Sachdeva et al. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136,905 hospitalizations in Get With The Guidelines. American Heart Journal. January 2009.
https://tinyurl.com/4unhmr55
Ref 37: https://www.zoeharcombe.com/2025/03/polypill-statins-for-over-50s-says-founder/
Ref 38: https://www.polypill.com/Home/FAQ
Ref 39: Kannel WB, McGee D, Gordon T. A general cardiovascular risk profile: the Framingham Study. Am J Cardiol 1976.
Ref 40: Correlation coefficients range from -1 (the perfect opposite relationship) to +1 (the perfect positive relationship). A correlation coefficient of 0 indicates no relationship between two things. A score of 0.6, therefore, is quite a strong positive relationship between two things.
Ref 41: https://qrisk.org/
Ref 42: Hippisley-Cox et al. Derivation and Validation of QRISK, a New Cardiovascular Disease Risk Score for the United Kingdom: Prospective Open Cohort Study. BMJ. 2007. https://pubmed.ncbi.nlm.nih.gov/17615182/
Ref 43: https://www.zoeharcombe.com/2020/06/the-risk-of-cvd-over-the-next-10-years/

Bio

Adrian Soto-Mota, MD, PhD is a clinical researcher at the Metabolic Diseases Research Unit at The National Institute of Medical Sciences and Nutrition Salvador Zubirán (INCMNSZ). He obtained his M.D. at UNAM (2013) and specialized in Internal Medicine at (INCMNSZ). Afterward, he obtained his Ph.D. at the University of Oxford (2021) and his Professional Certificate in Data Science that same year. Currently, he also serves as an Internal Medicine Consultant at (INCMNSZ), and as a Clinical Sciences Lecturer at the Monterrey Institute of Technology and Higher Education. His research interests are Human Metabolism (focused on Ketone Metabolism), Data Analysis, and Evidence-Based Medicine. He is an active member of the American College of Physicians.

I have contacted Adrian a couple of times for help with my Monday notes – especially on statistics – and I met him very briefly once at Dr Isabella Cooper’s house in London. Hence I sent some queries about the recent paper to Adrian and Dave and Adrian kindly replied. Even more kindly he offered to do a zoom meet, so we could discuss the queries more effectively. We had such an interesting chat that I asked if Adrian would do a podcast. We recorded one a few days later (28th May 2025) and here it is for you to enjoy.

Introduction

Lean Mass Hyper Responder (LMHR) was the term developed by Dave Feldman to describe lean, fit, metabolically healthy people, who exhibit striking increases in cholesterol when adopting a ketogenic diet. The term LMHR seems to have first been proposed by Dave in a blog post in July 2017 (Ref 1).

I took a detailed look at the LMHR research following a recent paper published in the first week of April 2025 (Ref 2). The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial.” Professor Adrian Soto-Mota was the lead author. Co-authors of interest included Dave Feldman and Dr Nick Norwitz. Professor Matthew Budoff was the senior author presiding over the research.

While reviewing the latest paper and previous LMHR research, a number of observations and queries arose. Points 3 to 7 were critiques from a rapid response pre-print paper (Ref 3); the other points were mine.

1) The “cut points” that define the LMHR have changed over time. Originally, they were LDL-C of 200 mg/dL (5.2 mmol/l) or higher; HDL-C of 80 mg/dL (2.1 mmol/l) or higher; and triglyceride levels of 70 mg/dL (0.79 mmol/l) or lower (Ref 4). In the recent paper, the “cut points” were LDL-C of 190 mg/dL or higher (not 200); HDL-C of 60 mg/dL or higher (not 80); and triglyceride levels of 80 mg/dL or lower (not 70).

2) Participants were recruited for this research via a web survey seeking people meeting the LMHR profile. The paper by Norwitz et al (November 2021) separated respondents to this web survey into 100 LMHRs and 448 non-LMHRs (Ref 5). At the time of that paper, the original cut points applied. Under the revised cut points, on average, the non-LMHRs would be LMHRs. From male/female numbers, we also know that the 100 in the recent paper were not the same as the 100 in the November 2021 paper. How 100 people were chosen at different stages of the LMHR research was not clear.

3) The pre-registered primary outcome (percent change in non-calcified plaque volume (NCPV)) was not presented as a value in the paper.

4) Having since been informed about the percent change in non-calcified plaque volume (NCPV), it’s comparatively high. The percent atheroma volume (PAV) is also high.

5) The main finding from the paper about ApoB (and LDL-C) not being associated with plaque progression cannot be made (this note explains why that was claimed).

6) The main finding from the paper title “Plaque begets plaque” is not new or explanatory.

7) The research should have been called the KETO-CTA Study not the KETO-CTA Trial.

8) A paper published by Budoff et al in June 2024 compared 80 people from the KETO-CTA trial with matched people from the Miami Heart Study (Ref 6). At least 10 of the 80 KETO-CTA trial participants had LDL-C levels below 200 mg/dL. Most of these were visibly below 190 mg/dL. The lowest LDL-C level seemed to be around 120 mg/dL.

9) The association between LDL-C and percent change in non-calcified plaque volume (NCPV) was not examined/presented.

10) Has the research question been answered? The research question for the LMHR team was... some lean, fit, metabolically healthy people experience striking increases in cholesterol (total cholesterol and LDL-Cholesterol) when they adopt a ketogenic diet. Other markers are good (often excellent) – does the rise in cholesterol matter?

Questions in the podcast (with approximate time stamp)

03.45 How did you (Adrian) get involved in the LMHR research?

06.00 What are Lean Mass Hyper Responders? Is that the best description of them?

10.50 Why does LDL-C go up in some people on a keto diet? What’s the Lipid energy model?

19.05 How rare are they (LMHRs)? How difficult was it to find 100?

24.00 This led to the point that the LMHR ‘lipid triad’ of high LDL-C but high HDL-C and low triglycerides has been assumed to define a healthy person and it might not.

Did the added eligibility criteria (not smoking, BP, hbA1c etc) define a healthy person?

30.10 The recent paper was criticised for not sticking to the variables set out in the clinical trial registration and study design and methodology papers. (LDL-C and mean changes in non-calcified plaque volume (NCPV)). Was there a reason for this?

41.20 On the ApoB vs LDL-C – was that something you discussed as a research team or was that something you led on as the main author of the last paper?

44.00 What were the main findings of the recent study? (Below are the four points that Adrian shared in the pre-zoom, as they were succinctly presented).

i) LMHRs are highly heterogeneous; (the lipid triad does not define a healthy person)

ii) The best plaque predictor is plaque.

iii) Diet doesn’t seem to predict plaque.

iv) The previous three points remind us that CVD research needs to look beyond lipids.

53.20 It has been argued that the people studied are at the 99th percentile of LDL-C, ApoB, low carb intake etc. There could be a relationship between two variables across the whole spectrum that might not be found if we just look at those at one extreme.

01.02.00 Have we answered the research question? Do we think people who go on a keto diet and their LDL-C goes up by more than 50% have anything to worry about?

01.07.42 What future research is planned or has been started already?

01.13.30 Is there anything we haven't covered?

The 10 points - discussion and video

Executive summary

* An unusual and clever study has been published using healthcare data from Wales.

* Wales introduced a shingles vaccine policy that had an absolute cut-off date. People born before 2 September 1933 were not eligible for a shingles vaccine; people born after this date were eligible. The vaccine roll out started on 1 September 2013 when the oldest eligible people would have been 80.

* The researchers compared eligible people with ineligible people using the latter as a control group in effect. They claimed that those eligible for the vaccine had a reduced incidence of dementia diagnosis in the 7-year follow-up (absolute risk reduction of 3.5 percentage points and a relative risk reduction of 20.0%).

* The control group is not those who weren’t eligible but those who were eligible and didn’t attend. This was not mentioned let alone adjusted for.

* There were other issues:

Executive summary

* A systematic review (look at all studies) and meta-analysis (pool them together) has been published. It examined statins + ezetimibe (a drug that inhibits cholesterol absorption from the intestine) with statins alone. The authors had substantial drug industry conflicts.

* Unusually (i.e., not best practice) the study pooled randomised controlled trials (RCTs) with population studies.

* It claimed that statins + ezetimibe lowered cholesterol more than just statins. That's not surprising.

Bio

Dr Gary Fettke is a retired Tasmanian Orthopaedic Surgeon and a vocal proponent of nutrition being a major component of prevention and management of modern disease.

He is a staunch advocate for reducing ultra-processed food in the diet and recommends a nutrient rich ketogenic or LCHF lifestyle. Gary calls this Low Carb Healthy Fat, rather than Low Carb High Fat.

In 2014, Gary was targeted by the processed food industry for his public opinion on the perils of excessive sugar consumption and for showing the potential to put patients with Type 2 diabetes into remission. This culminated in him being ‘silenced’ by the AHPRA Medical Board (Australian Health Practitioner Regulation Agency). Gary and Belinda fought this outcome, at great emotional and financial cost. Their resilience prevailed and 2018 saw a clearance of those charges with a full apology from the Medical Board.

Gary has a broad understanding of the vested interests shaping dietary and health guidelines, and particularly those affecting the animal-based food sector.
He is active on social media across a variety of platforms. The Public Health and AHPRA narrative have been politicised for decades. The capacity to debate and question policy has been taken away from the primary health providers trying to individualise patient care.

Gary has remained a vocal, independent voice seeking transparency and a truthful narrative around health, nutrition, and in particular preventative management across a variety of health spectrums. He continues to support the rights of free speech as ‘Science evolves by being challenged. Not by being followed.’

Show notes

Andy and I have known Gary since we first met at a conference in Cape Town in 2015. We have since become friends with him and Belinda. Because we zoom as a four quite often, I knew this chat might go anywhere and it did. Gary is a big thinker and is fascinating on many topics. In this hour and a bit, we covered…

- How we met and what we’ve got up to as a four since.

- Finding our tribe.

- How Gary got into the health arena.

- What Gary’s dietary guidelines would be.

- Belinda’s work on the conflicts behind the guidelines (from cereal companies to Seventh Day Adventists).

- Why can’t people see that the guidelines are unhealthy? And, therefore, realise that public health is not about making us healthy?

- Who the dietary guidelines are really for and how that opened the door to Low Carb Healthy Fat for diabetes in Australia (and who has been behind that achievement).

- What happened in Australia during Covid?

- Why weren’t possible treatments considered?

- Why can’t doctors see/admit the legacy that has been left from the Covid interventions?

- If you were given the role that Trump plans for RFK in Australia, what would you do?

Here is the video of our discussion

Executive summary

* Lean Mass Hyper Responder (LMHR) was the term developed by Dave Feldman to describe lean, fit, metabolically healthy people, who exhibit striking increases in cholesterol when adopting a ketogenic diet.

* Last week we looked at the latest paper from the LMHR research team. The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial.”

* In last week’s note, we reviewed how the definition of LMHRs had changed over time and characteristics of the 100 participants involved in the research along the way. We also noted the aim and primary outcome of the KETO-CTA Trial, as documented in the February 2023 clinical trial registration and the June 2024 study design and methodology paper.

* This week we look at the results from the KETO-CTA trial and five critiques that have been made in a rapid response pre-print paper. These five themes reflected much debate on social media.

* The main results were that plaque progression:

i) was not associated with baseline ApoB; change in ApoB; or total LDL-C exposure.

ii) was associated with all baseline plaque metrics (coronary artery calcium, NCPV, total plaque score, and percent atheroma volume).

* The key factor of interest in LMHRs from the outset has been the level of LDL-Cholesterol. The recent paper did not report this measure; it focused instead on ApoB and a new outcome of interest – LDL-C exposure. Why?

* The five critiques can be summarised as:

1) The pre-registered primary outcome was not presented as a value in the paper.

2) Having since been informed about the percent change in non-calcified plaque volume (NCPV), it’s comparatively high. The percent atheroma volume (PAV) is also high.

3) The main finding from the paper about ApoB (and LDL-C) not being associated with plaque progression cannot be made.

4) The main finding from the paper title “Plaque begets plaque” is not new or explanatory.

5) The research should have been called KETO-CTA study not KETO-CTA Trial.

This note goes through each of these critiques and the authors’ responses, to try to assess if they were valid.

* I close by reiterating the research question for the LMHR team and trying to evaluate whether it has been answered.

Introduction

Last week we looked at the latest paper from the Lean Mass Hyper Responder research team. The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial” (Ref 1). The lead author was Professor Adrian Soto-Mota. The senior author was Professor Matthew Budoff. Other authors of interest include Dave Feldman and Dr Nick Norwitz.

This week we are looking at the results from the latest paper and the reaction to those results. This is my 735th Monday note. It’s the first where I have spent as long reading threads on X (twitter) as I have reading academic literature. The debate about this research is being played out on social media.

In an interview about the research and the paper, the senior investigator, Professor Budoff, said “I presented the initial data at the World Congress of Insulin Resistance & CVD. The presentation was filmed and that YouTube video had over a million views, where I probably have hit maybe 100 views on any other video I've ever made” (Ref 2).

The paper attracted a lot of attention because it sought a lot of attention. There are pros and cons of this. More people check X than read academic publications. Social media can extend the reach of research but social media can also be a ‘cesspit’, for want of a better word. Some of the critiques were well made and valuable. Some were nasty and vitriolic. There was no need for the latter and I did feel for the team for the abuse that they received from some people.

Executive summary

* Lean Mass Hyper Responder (LMHR) was the term developed by Dave Feldman to describe lean, fit, metabolically healthy people, who exhibit striking increases in cholesterol when adopting a ketogenic diet.

* This week's note looks at the recent (April 2025) paper from the LMHR research team. The paper was called “Plaque begets plaque, ApoB does not: Longitudinal data from the KETO-CTA Trial.”

* I have written previously about LMHRs and the Lipid Energy Model – the hypothesis for why this phenomenon happens.

* While researching the debate around the latest paper, I went back to some previous work by the LMHR team.

1) The “cut points” that define the LMHR have changed over time. Originally, they were LDL-C of 200 mg/dL (5.2 mmol/l) or higher; HDL-C of 80 mg/dL (2.1 mmol/l) or higher; and triglyceride levels of 70 mg/dL (0.79 mmol/l) or lower. In the recent paper, the “cut points” were LDL-C of 190 mg/dL or higher (not 200); HDL-C of 60 mg/dL or higher (not 80); and triglyceride levels of 80 mg/dL or lower (not 70).

2) Participants were recruited for this research via a web survey seeking people meeting the LMHR profile. The paper by Norwitz et al (November 2021) separated respondents to this web survey into 100 LMHRs and 448 non-LMHRs. At the time of that paper, the original cut points applied. Under the revised cut points, on average, the non-LMHRs would be LMHRs. From male/female numbers, we also know that the 100 in the recent paper were not the same as the 100 in the November 2021 paper. How 100 people were chosen at different stages of the LMHR research was not clear.

* The eligibility criteria define a rare and specific person. The LMHR profile may have other defining characteristics that could impact coronary artery disease and which haven’t been addressed (exercise, stress/personality type, alcohol, supplements etc).

* The research has generated much debate on X. Next week's post will review the results and the reaction.