I was on the circulation list for a recent email entitled “Breast cancer: 2 peaches/week 41% lower risk”.
The email opened by saying :
“Women who ate two servings of peaches per week had a 41% lower risk of breast cancer over the next 24 years according to a study from the Harvard School of Public Health in Boston, Massachusetts, USA.
“Women who ate one serving of blueberries per week had a 31% lower risk of breast cancer over the next 24 years.
“This study followed 75,929 women (part of The Nurses’ Health Study), 38- to 63-years-old at baseline, and followed them for up to 24 years.”
Here is the original paper. (Ref 1)
My first reply was
Association, not causation.
Relative risk, not absolute.
Nonsense, not science!
The more considered reply develops these further
Association, not causation
As Dr Malcolm Kendrick beautifully says “Association does not prove causation, but lack of association disproves causation”.
The way that science should work is that epidemiology/observational studies suggest association and then possible associations should be tested in a sufficiently powered, long enough, randomised controlled trial to see if there could be causation – changing the hypothesised thing alone. We have largely abandoned this step in science since, and including, the Seven Countries Study. We now see an overweight sedentary person and assume that being sedentary made them overweight. What about being overweight made them sedentary? What about a lousy high-carb-following-gov-advice diet made them both overweight and low in energy? What about a thyroid condition led to both?
If we observe association, we should look for a plausible mechanism to see if the intervention would be worth testing. If (to use another Dr Malcolm fab example) we push someone out of an airplane without a parachute we can do an n=1 to say that being pushed out of an airplane without a parachute causes death and jumping out of a plane with a parachute rarely causes death and so the parachute has a plausible mechanism in life extension.
What is the plausible mechanism with peaches and breast cancer?! I would not be surprised if women eat more peaches then men and substantially more women develop breast cancer – so where does that leave us? Is it antioxidants? Coffee and cocoa powder are massively higher in antioxidants than fruit so there could be a better intervention. Is it general nutrition? Fruit is pretty rubbish for nutrients compared to animal foods and dark green veg. I can’t even see a plausible mechanism.
Relative vs. Absolute risk
This study followed 75,929 women, 38- to 63-years-old at baseline, for up to 24 years. During this time there were 792 cases of post-menopausal breast cancer recorded. The study title did clarify that it was solely looking at post-menopausal cancer. The email I received didn’t clarify this.
That’s an incident rate during the 24 year study of 1.04%.
In any one year, the incident rate was 0.043%. Can you even get your head round such a tiny number?
So now we introduce the relative risk. The following table is extracted from Table 3 in the paper. It tells us the incidents among consumers of peaches/nectarines – don’t forget the nectarines.
The study used women who never eat peaches/nectarines as the base line. The baseline is given a risk ratio of 1.0. Relative to this group, those who had peaches up to a couple of times a month had exactly the same risk ratio – 1.0. Those who had peaches more than a couple of times a month but fewer than once a week had virtually the same risk ratio: 0.98. Those who had peaches between once and twice a week had a risk ratio of 0.87 BUT the confidence interval was 0.66-1.15, which includes the baseline number of 1.0 and thus we can’t be sure that we are not seeing the same result as at baseline and therefore we call this not significant.
The only significant result (where the confidence interval excludes 1.0) is the two or more peaches/nectarines a week:
||Up to 2/mth
||>2/mth to <1/wk
||1/wk to <2/wk
|Breast cancer cases
|Adjusted relative risk (RR)
1.0-0.59 = 0.41, which is where the 41% headline comes from.
The incidents and person years tell us the following:
We know from the overall numbers (792 incidents from 75,929 women in 24 years) that, in any one year, the incident rate was 0.043%.
This incident rate was 0.062% for never eat peaches and 0.038% for eat more than 2 peaches a week.
Are you any more able to get your head round those numbers?
No – me neither.
Now how does the 41% risk headline, with no explanation offered, look?!
Table 3 also tells us that they did not adjust for education, which is a well known marker for being better off…
If this study told us anything (apart from the fact that researchers continue to NOT understand association vs causation and relative vs absolute risk) it may have confirmed what we already know, which is that better off people enjoy better health.
Take UK regional life expectancy. The lowest for men and women occurs in Glasgow with life expectancy of 71.6 and 78 years respectively. The highest for men and women is found in Kensington and Chelsea – 85.1 for men and 89.8 for women.
Another interesting finding of the study was that there was not even an association with breast cancer and other fruits and vegetables. None. Zippo. Only peaches/nectarines and blueberries have magic breast cancer prevention plausible-mechanism-unknown properties. Peaches are posh fruits – P for posh. Passion fruit, Papaya, PawPaw, Pequi, Persimmon, Pewa, Pineapples, Pitahaya, Pitomba, Pomegranates, Pashminas (ho ho).
Q) Would you more likely find peaches in a fruit bowl in Kensington and Chelsea or in Glasgow?
Did the researchers not think – we’ve just reinforced better off = better health? And we should research health inequalities? No – the researchers want to carry on researching nonsense.
The abstract ends with these words: “These results are considered exploratory and need to be confirmed in further studies.” That’s academic speak for “we need funding, so please give us some money.” Bet the Blueberry Association has been in touch already.
Ref 1: Fung TT, Chiuve SE, Willett WC, Hankinson SE, Hu FB, and Holmes MD. Intake of specific fruits and vegetables in relation to risk of estrogen receptor-negative breast cancer among postmenopausal women. Breast Cancer Res Treat, 2013 Apr; 138(3): 925-930.
This is a short blog about a new game, as I see it…
The headlines on 6th August 2014 were that millions more people should be taking aspirin daily for a minimum of 5 years, ideally 10, heck – make that for ever…
The original article is here. The BBC reported the story as “Daily aspirin ‘cuts bowel and stomach cancer deaths.'” Of course nothing cuts deaths – we are all going to die – but let not the facts get in the way of the story.
The article is interesting in that it’s the first that I’ve seen to detail explicitly how many people might be saved and how many might be killed by taking aspirin. Yes, killed. Check out figure 1 and the researchers have estimated how many men and women they claim will be saved by taking aspirin and how many deaths they forecast “due to stroke, GI bleeding or peptic ulcer caused by aspirin.”
On balance, they say more will be saved than killed and so an aspirin a day for loads of people will kill a few here and save more there. And here’s the big point. Aspirin is as cheap as chips, cheaper than chips no doubt, so why would you not want to put every over 50 year old on aspirin (the age will no doubt get lowered) if you can save more than you kill?
Conflicts of interest
The first thing I check in any article is declarations of interest. If someone tells me walnuts are going to save lives and they and/or the study were funded by the walnut foundation, I am inclined not to take much of what I read very seriously.
In this article the disclosure states: “JC [that’s the lead author – the one who was on the TV that day]: Member of the Bayer advisory board. JB: Consultancy for Bayer Pharma. Research funding from Bayer Pharma. A stockholder and medical director in QuantuMDx, a new medical devices company which will develop point of care pharmacogenetic testing. Aspirin sensitivity is one of company’s targets. JAJ: Consultant to Astra-Zeneca, Dr Falk Pharmaceuticals, Chief investigator of AspECT trial and ChoPIN trial. PMR: Has received honoraria for talks, advisory boards and clinical trial committees from several pharmaceutical companies with an interest in antiplatelet agents including Astra-Zeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, Biotronic, Johnson & Johnson and Servier, and is on the executive committee of the ARRIVE trial. Research funding from Boehringer Ingelheim. All remaining authors have declared no conflicts of interest.”
If all the companies with an interest in antiplatelet agents (things that aim to prevent blood clotting) – Astra-Zeneca, Bayer, Boehringer Ingelheim, Sanofi-BMS, Biotronic, Johnson & Johnson and Servier etc – were seen to be behind a paper saying “give millions of people antiplatelet agents”, we would probably see through this and wonder about the drug cost and not just the cost of those ‘killed’ by stroke and stomach bleeds weighed up against those ‘saved’ from cancer.
So here’s the plan:
1) Do a paper about the benefits of the cheap, generic, everyone-has-it-in-the-medicine-cabinet, friendly, aspirin.
2) Call for millions of people to be given cheap aspirin for years and years and a humongous medication opportunity has just been created.
3) As soon as possible after the aspirin prescribing occurs, show that the expensive, branded, drug company antiplatelet agents are so superior to aspirin that to keep people on the generic, cheap aspirin would be a crime. Particularly, I suspect, having highlighted the stomach bleed/ulcer problems – these branded drugs will no doubt be better at avoiding stomach problems. Then millions of people will be switched to the patented drugs and stay on them for decades.
4) Make riches beyond wild dreams.
Watch this space…
The CTSU is the Oxford Clinical Trial Service Unit. Where this ends and the CTT (Cholesterol Treatment Trialists) Collaboration begins or where CTT ends and where Sir Professor Rory Collins and Colin Baigent and co. begin or end, I know not. One gets the impression that the web between the parties is not intended to be clear.
This is the group that promotes statins. This is the group that holds data on statin side effects, which it won’t share with doctors and patients who would like to know about these statin side effects. Pause to digest that for a second. There is clinical trial information about what the most prescribed drugs in the US and UK could do to humans and researchers refuse to share it.
It was the lead member of this group, Sir Professor Rory Collins, who recently attacked the BMJ for publishing two articles that referenced the same peer review article finding about statin side effects. Not only did Collins attack the BMJ he went entirely outside the journal’s normal process and demanded that the two articles be retracted. The first was by John Abramson, Harriet Rosenberg, Nicholas Jewell and James M Wright; the second was by Dr Aseem Malhotra.
I covered Collins’ attempt at censorship in this post (after the Dr Maryanne Demasi Catalyst bit). In writing the post I found a declaration of interest involving over £115 million by CTSU member, Colin Baigent, repeatedly mentioning Collins/CTT/CTSU. This is in fact less than half the funding that the CTSU has received from commercial organisations. The MRC (Medical Research Council) and BHF (British Heart Foundation) funding, which they declare more readily, is in addition to the eye watering sums that they get from the hands that feed them.
The documents published as part of the panel review
The BMJ’s editor, Dr Fiona Godlee, called for an independent panel to be set up to investigate Collins’ demands. The full report of the panel is here, (published 1 August 2014). The outcome was that the panel found that neither the Abramson et al paper nor the Malhotra paper should be retracted.
The far more interesting outcome was the supplementary information that was published alongside the panel’s full report, in the BMJ spirit of openness and honesty. In particular, some “not for publication” letters written by Collins. If you make such serious demands, that a world regarded journal retract two papers, you don’t get to call the shots on what remains hidden. Hence much “Supporting Documentation” has been published by the panel called upon to investigate Collins’ demands.
Letter SP17, dated 31 March 2014, has an interesting “P.S.” (direct Collins’ quotations in blue and italics for ease of reading).
“P.S. Conflicts of interest: There have been a number of comments in the BMJ and elsewhere about potential conflicts of interest in this area, so it may be helpful to provide you with some background. CTSU’s coordination of the Cholesterol Treatment Trialists’ Collaboration (CTTC) has been funded by the Medical Research Council and British Heart Foundation, without any commercial funding.”
You can read the full P.S., for it is quite long. It ends as follows:
“As we are all aware, a range of potential conflicts of interest exist and it is important that there is transparency (as, for example, with the BMJ’s advertising and sponsorship revenue from vaccine manufacturers which it inadvertently omitted to report when commenting on the MMR vaccine and autism story). With respect to CTSU, we have had a policy for more than 20 years of not accepting honoraria, consultancy or other payments directly or indirectly from industry, except for research grants and reimbursement of travel and accommodation to take part in scientific meetings (see attached)… Please could you let me have details of all conflicts of interest that have been declared by the authors of the Abramson and Malhotra papers (including the size of all payments that they have received for any statin-related work)?”
The conflicts of interest for the Abramson article were openly declared at the end of the article (as is BMJ policy) (JDA is John D. Abramson and NJ is Nicholas Jewell):
Competing interests: JDA and NJ serve as experts for plaintiffs’ attorneys in litigation involving the drug industry (including a statin). JDA has received payment for lectures from several universities, medical schools, and non-profit organisations. He was formerly executive director of health management for Wells Fargo Health Solutions.
The conflicts of interest for the Malhotra article were openly declared at the end of the article (as is BMJ policy). There were none to declare.
Competing interests: None declared.
Letter SP18, dated 14 April 2014, reiterated demands for the conflicts of interest of Abramson and Malhotra to be declared. “Please would you let me have the details of all conflicts of interest for Abramson et al and Malhotra, including the amounts of any payments that they have received for any statin-related work? This is information that should quite properly be in the public domain. In a spirit of reciprocity, I have attached the details of all grants from industry to CTSU for our research covering the past 20 years and more…” You’ll find this item – SP21 - in the supplementary information. If you open one link in this whole blog, make sure it’s this one.
This is priceless. “In a spirit of reciprocity, I have attached the details of all grants from industry to CTSU for our research covering the past 20 years and more…” Just look at that list. It doesn’t even include funding from the MRC, Cancer Research-UK or the BHF. It’s difficult keeping track of all the millions but I got to £268 million give or take a few hundred thousand. Plus, as Hannah Sutter discovered here, (point 4 especially), the MRC seems to be an indirect delivery mechanism for further pharmaceutical funding.
Who is being open and honest here?
Abramson & Malhotra declared their interests openly in their original articles, the latter having nothing to declare.
On 31 March 2014, Collins demanded “details of all conflicts of interest for Abramson et al and Malhotra” when all he needed to do was read them at the end of the articles to which he so objected. In the same letter, Collins told the BMJ “CTSU’s coordination of the Cholesterol Treatment Trialists’ Collaboration (CTTC) has been funded by the Medical Research Council and British Heart Foundation, without any commercial funding” (my emphasis).
Just two weeks later, Collins sent the BMJ “all grants from industry to CTSU for our research covering the past 20 years and more…” “In a spirit of reciprocity...” The commercial funding came to c. £268 million.
Does that seem open and honest to you?
In the most recent statin article listing Collins as an author on pubmed, scan all the way down to “funding” and the funding declaration opens with info on the China part of the study. The bit relating to Collins/CTSU etc states “the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at Oxford University also receives core funding for it from the UK Medical Research Council, the British Heart Foundation, and Cancer Research UK.” What about the £268 million?
Does that seem open and honest to you?
I thought I’d see when Collins last wrote for the BMJ and what he declared when he did so. He wrote about confidential data of all things! Sadly not on open view, but I have seen a copy of the full paper. At the end of the article we see the following:
Competing interests: None declared.
What, not even the fact that you have commercial agreements in place prohibiting the sharing of data? i.e. keeping that data confidential?
Does that seem open and honest to you?
The real scandal
I have followed this saga with interest because it has been a saga – of arrogance, accusations and demands. We must not let the Eastenders style drama detract from what the real scandal is here. The real scandal is that a research body holds data, which could provide vital information for patients and doctors about the serious adverse effects for the most widely prescribed drugs in the Western world and the body will not release the data. This blog confirms this fact. See the email from Colin Baigent to Dr Maryanne Demasi (the Catalyst Programme presenter who has also been censored) on 24 Sep 2013 10:44:01: “It is important to recognise that data from participating trials are not owned by the Collaboration [CTT], but remain the property of the trial sponsors, so we are not able to provide unlimited access to the combined database.”
I interpret this as – we receive £268 million from trial sponsors and it is not in their interests for side effect data to be shared. And if some patient loving cardiologist, with no such conflicts of interest, dares to suggest that statins have side effects (when we hold that information and won’t tell him) we’ll bypass the BMJ process and demand retraction.
My contempt for Collins, Baigent, the CTSU and the CTT – wherever the web lies – knows no bounds.
This is extracted from: “The Obesity Epidemic: What caused it? How can we stop it?”
Marjorie R. Freedman, Janet King, and Eileen Kennedy wrote an article called “Popular Diets: A Scientific Review”, where 17 studies of weight loss with different macro nutrient (carbohydrate, fat and protein) composition, were reported with the concomitant results.[i] The authors stated that “no published studies are excluded”, so I have assumed that these are the only studies between 1956 and 2001. The three authors concluded “Caloric balance (calories in vs. calories out), rather than macro nutrient composition is the major determinant of weight loss.”
Yet I analysed all the data for these 17 studies and found no relationship between low calorie intake and high weight loss (0.009 correlation coefficient), but a significant relationship between low carbohydrate intake and high weight loss (0.79 correlation coefficient) (Tables below). How can the authors have concluded as they did, unless they set out to prove an already held point of view?
“Popular Diets: A Scientific Review”[i]
||Authors & publication
||# of people
||grams lost/ day
||Rickman, JAMA (1974)
||Benoit et al, Ann Intern Med (1965)
||Yudkin & Carey, Lancet (1960)
||Fletcher, Br J Nutr (1961)
||Lewis et al, Am J Clin Nutr (1977)
||Kasper et al, Am J Clin Nutr (1973)
||Evans, Nutr Metab (1974)
||Golay et al, Int J Obes relat Metab Disord (1996)
||Young, Am J Clin Nutr, (1971)
||Golay et al, Am J Clin Nutr (1996)
||Cedarquist, J Am Diet Assoc (1952)
||Worthington & Taylor, J Am Diet Assoc (1974)
||Rabast et al, Int J Obes relat Metab Disord (1979)
||Rabast et al, Nutr Metab (1978)
||Wing et al, Int J Obes relat Metab Disord (1995)
||Alford et al, J Am Diet Assoc (1990)
||Baron et al, Am J Public Health (1986)
* 21 studies were included in tables 5a and 5b in the paper. Three had no results for weight change, so could not be included (Kekwick 1957, Bortz 1968 and Krehl 1967).
* I excluded Larosa et al (1980), as the table said that the study was for 12 weeks when, in fact, the article and the original journal revealed that the subjects followed their normal diet for two weeks at the start and two weeks at the end of the 12 week period. We cannot determine what the weight loss per day was in relation to a measured carbohydrate and calorie intake period.
* The 17 remaining studies are above. There was a material error in the article. This has been corrected in the table above, as follows: Study 8 (Golay et al) – the weight loss in table 5a is given as -8.0 kilograms over 6 weeks, which was commuted to -111 grams per day in table 5a. This is wrong and -8.0 kilograms over 6 weeks equates to -190 grams per day. However, the table appears to be wrong in more way than one and the original journal (and the text in the article) state that the weight change for the group on 37.5 grams CHO was -8.9 kilograms +/- 0.6 kilograms. I have taken the mid point of -8.9 kilograms and this equates to -212 grams per day. This is the number in the table for this appendix and the number I have used for the correlation.
* A number of ranges were taken at mid point level, as follows:
– Study 7 (Evans) – the range of weight loss was given as -76 to -119 grams per day, so I took the mid point of -97.5 grams per day;
– Study 11 (Cedarquist) – the range of weight loss was given as -78 to -150 grams per day, so I took the mid point of -114 grams per day.
* Five of the studies were directly comparable isocaloric studies i.e. the studies had parallel groups on a different carbohydrate level and the same calories per day (these are studies 6, 8, 10, 12 and 14). In every such isocaloric study in the article, the weight loss was substantially higher in the low carbohydrate group than in the higher carbohydrate group. At the highest calorie intake (Kasper et al, study 6, 1707 calories per day), the group consuming 56 grams of carbohydrate per day lost 300 grams per day vs. the 156 grams of carbohydrate per day group, which only lost 50 grams per day. This supports Kekwick and Pawan’s findings that large numbers of calories can be consumed and weight still be lost with a low carbohydrate diet composition.
Correlation between (low) calories & (high) weight loss
||Benoit et al
||Yudkin & Carey
||Lewis et al
||Kasper et al
||Golay et al
||Golay et al
||Worthington & Taylor
||Rabast et al
||Rabast et al
||Wing et al
||Alford et al
||Baron et al
N = the number of pairs of scores (17)
∑xy = sum of the products of paired scores (-6,094,862)
∑x = sum of x scores (21,373)
∑y = sum of y scores (-4,854.5)
∑x2 = sum of x scores squared (28,593,253)
∑y2 = sum of y scores squared (1,865,057)
r = 0.009
Correlation between (low) carbs & (high) weight loss
||Benoit et al
||Yudkin & Carey
||Lewis et al
||Kasper et al
||Golay et al
||Golay et al
||Worthington & Taylor
||Rabast et al
||Rabast et al
||Wing et al
||Alford et al
||Baron et al
N = the number of pairs of scores (17)
∑xy = sum of the products of paired scores (-147,786)
∑x = sum of x scores (711.5)
∑y = sum of y scores (-4,854.5)
∑x2 = sum of x scores squared (40,158.25)
∑y2 = sum of y scores squared (1,865,057.25)
r = 0.79
I reiterate, how can the authors have concluded as they did, unless they set out to prove an already held point of view?
[i] Marjorie R. Freedman, Janet King, and Eileen Kennedy, “Popular Diets: A Scientific Review”, Obesity Research, (March 2001).
On Wednesday February 12th 2014 the UK National Institute for Health and Care Excellence (it used to be the National Institute for Clinical Excellence, hence NICE) published draft guidelines on statins. The guidelines have been published today on 18th July 2014. NICE recommends lowering the threshold for giving statins to healthy people with no symptoms of heart disease to anyone deemed to have a 10% risk of developing heart disease over the next 10 years.
All shall be statinated. Resistance is futile
This risk calculation is so heavily dependent on age, by the way, that EVERYONE has a date at which they should be statinated, as Dr Malcolm Kendrick explains here playing with the American risk factor toy, which came out in November 2013.
You can play with the QRISK2 UK toy here to your heart’s content. I’ve just worked out my “must be statinated age”. I’m a non-smoker, no diabetes, no history of heart disease, no atrial fibrillation, no kidney disease, no arthritis, (very) low BP and a BMI of 20-21. I have no idea what my cholesterol and HDL is and could not care less. So I entered what the NHS considers ideal for a cholesterol/HDL ratio of 4 (Honestly – where do they get this nonsense?!)
The result? If I were aged 64 today, my risk over the next 10 years would apparently be 8.2%. Aged 65 it would be 9%. Aged 66 it would be 9.8% and aged 67 is would be 10.7%. (Look how it’s just going up by almost 1% per year). So – somewhere between my 66th and 67th birthday (thankfully a long way away!) I should be on statins.
The key priorities for implementation say that everyone up to the age of 84 should be targeted. Don’t the powers-that-be read patient leaflets? Here’s the patient leaflet for Liptor, cautioning that Lipitor may not be suitable for anyone over the age of 70. That’s because there is much evidence for low cholesterol being especially bad in the elderly – if you fancy living longer that is.
So we all have a statin use-by date – super healthy as I am, mine is 66-67.
Statin conflicts of interest
It took me less than an hour following the NICE publication of the draft guidelines in February to uncover the conflicts of interest of the panel – 8 out of 12 people having clear connections to drug companies. I blogged about it for Health Insight UK here. The Sunday Express covered the conflicts here. And an extraordinary open letter from doctors and academics to NICE and the UK Secretary of State for Health, Jeremy Hunt, raised conflicts as one of many concerns about the then proposed (now finalised) statin guidelines.
I wrote to Jeremy Hunt on 17th February 2014 about the NICE conflicts. Someone replied on 28th February, on Hunt’s behalf, to say “NICE, as an independent body, has its own procedures in place for managing conflicts of interest.” The letter suggested that I raise my concerns with Sir Andrew Dillon – Chief Executive of NICE. So I did. I wrote to him on 5th March, chased on the 7th April and finally received a reply from a communications executive dated 23rd April.
Having set out the details of the conflicts of the Guidelines Development Group in my letter, the four questions I asked were as follows. I’ve summarised the answers I got back from NICE below each question:
Q1) Please can you confirm if you knew about the conflicts of interest on this Guideline Development Group?
Q2) Do you agree that the conflicts, in this case, negate the claim of NICE to be independent and unbiased?
Q3) What action will be taken to redress the bias and conflict in this group and the publication that it produced?
Q4) What steps will be taken to restore NICE to the body it claims to be: “evidence based guidance … created by independent and unbiased advisory committees.”
NICE’s position incredibly seems to be – people just need to declare conflicts and then we carry on knowing their conflicts.
Such arrogance no doubt inspired the academics and doctors to write that open letter, on 10th June, calling upon NICE to rethink their guidelines and to refrain from making these guidelines policy until all trial data (side/adverse effects especially) are shared. The latter are withheld by ‘researchers’ funded by the statin manufacturers under commercial arrangements made with the hand that feeds them.
NICE’s response to the open letter is detailed in the previous link. Probably best summed up by an unprofessional and bizarre mix of attack and defence, but overall dismissal.
And now for bariatric surgery guidelines and conflicts
As soon as I saw the headlines on 11th July 2014, announcing that Christmas had come early for the bariatric surgery industry, I suspected that conflicts would be discoverable (and I was not alone in this, receiving a call from a surgeon friend suspecting the same).
The NICE statement was published on line early that afternoon. Fewer than five minutes later, the conflicts were apparent. Follow the link through to details of the draft guidelines and you can see a link through to the “Guideline Development Group” and this reveals that four bariatric doctors and two bariatric surgery patients formed the substantive part of the group. One of the doctors is Head of Obesity and bariatric services at University College London Hospital.
The patients are not just patients – one particularly. Check out this article on Ken Clare who works for Gravitas (bariatric surgeons and clinicians) and runs a web site and forum, funded by Gravitas?, to help people who are considering surgery or have had surgery. Alexandra Blakemore was so pleased to have had surgery, she made a youtube video about it. I have stopped attending obesity conferences because the agendas have been infiltrated by the barbaric surgery industry and their spokespeople (paid and/or given free surgery?) to promote the procedure.
This is a disgrace. There is no way that NICE can continue to claim to be independent, let alone authoritative and evidence based. A guideline group should have NO conflicts whatsoever. A guideline group should be staffed with researchers and statisticians – ideally who know nothing about the drug/intervention in question. Then the data speaks entirely for itself and no prejudice (literally to pre-judge) can enter the debate.
The Nolan Principles of Public Life
I have been an Executive Director at the Welsh Development Agency (2002-2005) and a Non Executive Director at University Wales, Institute Cardiff (2006-2012) and the Wales NHS National Delivery Group (2009-2012). In all of these roles I was bound by The Nolan Principles of Public Life (selflessness,integrity, objectivity, accountability, openness, honesty and leadership). All public roles should carry the same obligation. In my public sector work, the way that conflict of interest worked was that – if you had any connection to any item on the agenda you declared this to the clerk/meeting secretary before, or at the start of, the meeting. When this item came up you left the room. You did not even stay in the room, as your position could inhibit free exchange of views. If your conflict was such that even being a member of the board would be inappropriate (i.e. you could gain in any way from your affiliation with the body), you would not be on the board. Full stop.
At the first meeting of the guideline development group, the conflicts were recorded and ‘addressed’ as follows: “The GDG members verbally declared their DOIs (as per the DOI register) and the Chair agreed there were no conflicts of interest therefore no action was required.”
You may need to read that twice. The group members declared their conflicts and the chair agreed there were no conflicts. This is the same NICE response to the statin conflicts. Yes we were aware of the conflicts, but we saw no problem in these conflicts.
NICE seems to think that one merely needs to declare a conflict and then it no longer need be deemed a conflict. To use a topical, if disturbing, analogy, this would be like Jimmy Savile declaring that he’s a paedophile and then being allowed to play with children because his conflict was known about.
The NICE approach to conflict is an utter disgrace and the Department of Health needs to intervene urgently to establish a medical advisory body that is genuinely independent and evidence-based. Not one that is staffing guideline development groups with conflicted majorities and then publishing the views of these drug/surgery representatives as policy for practitioners to be ordered to adhere to.
p.s. Thank you to The Independent on Sunday for giving me the opportunity to give my view on the bariatric surgery guidelines and conflicts…
On 10 June 2014 there were global headlines about a ‘condition’ called pre-diabetes. From the Mail telling us that “A third of adults have ‘borderline’ diabetes – but most don’t know: Rising tide of obesity means number who have ‘pre-diabetes‘ has trebled since 2006″ to the Huffington Post proclaiming “Most People In England Have Borderline Diabetes, New Study Reveals“. One third was never most people when I did proportions, but anyway.
Here is the summary of the study and findings from a journal web site and here is the original (full) article.
A quick review of the article should have made the media far more challenging, instead of just taking the press release headlines:
1) The study used data already gathered for Health Survey England (HSE), which started in 1991. The number of adults involved in the HSE, from whom blood samples were taken, was 7,455 in 2003; 6,347 in 2006 and 1,951 in 2009. I can’t find the numbers for 2011, but they are likely to be small if the trajectory continues. There are over 40 million adults in England. Using 2009 as a guide, projections on this concept of ‘pre-diabetes’ have been made based on 0.0048% of the population. I can’t get my head around such numbers.
2) People were diagnosed with pre-diabetes if they had glycated haemoglobin (an indicator of blood sugar levels) between 5.7% and 6.4%. This is the US guideline for ‘pre-diabetes’. The UK guideline is 6.0-6.4%. This would have over-predicted the idea of having a pre-condition.
3) The introduction to the full article in the BMJ is worth a read. The introduction notes that England set up a scheme to offer people aged between 40 and 74 a health check to try to pick up blood glucose concerns (and other things). Then it admits that “the scheme is controversial since randomised trial evidence does not show that health checks reduce morbidity or mortality.” i.e. these health checks made no difference to health or death. The article then notes the concern about “the extent to which medicine is extending the boundaries of illness through new definitions of disorders, with a consequent risk of treating more people than necessary.” I couldn’t have put it better myself. That should have been the headline.
The issues with the headlines on pre-diabetes aren’t, however, the main focus of this post. This post is about the fact that normal is being redefined as abnormal to the point that normal is no more. The whole concept of pre-diabetes is just one example and it’s by no means the first distortion in the diabetes world…
Aside from this created condition of pre-diabetes, the definition of diabetes itself has been manipulated. There’s a useful diagram here (scroll about half way down), which has a clear illustration of the game being played.
The curve in this graph is known as a “normal distribution”. This means that, when we plot the population, people are normally (typically) distributed as this curve indicates – most people are in the middle and fewer people at both ends. The peak of the hump indicates the average (mean and mode in this case if you like stats). The average fasting blood glucose level is 100 mg/dL (this is the US measurement – UK would be 5.6 mmol/L). Don’t worry about the mgs and the mmols – we’ll just call them US and UK measures from now on. So 100 (US)/5.6 (UK) is the true average of the population. There are very few people with a fasting blood glucose level of 50 (US) and about the same number of few people with a fasting blood level of 150 (US) – most people fall within the 60-140 range (US) (3.3-7.7 UK).
Then see what has happened. Diagnosis of diabetes used to occur at a fasting blood glucose level of 140 (US) 7.8 (UK). This is a number on that normal distribution curve and so is an entirely normal reading for a section of the population. Normal was redefined as high. But then it got worse. Back in 1997, high was re-re-defined as 126 (US) and another large segment of entirely normal people became abnormal.
The UK uses the same benchmark to diagnose diabetes. This states that diabetes is diagnosed at a fasting blood glucose level above 6.9 UK (126 US). If you look at what the UK thinks is normal, it is arguably worse than the US graph. The UK has defined normal fasting blood glucose levels as 4.0-5.9 (72-106 US). The true centre of the norm from the graph is 100. The range which captures most people is thus 80-120 – not 72-106.
Normal is not normal. The medical world has overruled the human population and decreed that normal is not normal. Normal is now high and people shall be treated accordingly. Now that we have pre-diabetes on top, joy of joys, we can start medicating people even sooner than our re-re-defined norm would otherwise let us drug them. (Or we can give them ‘base your meals on starchy foods’ dietary advice and speed up their pathway to type 2 diabetes.)
This doesn’t just happen in the world of diabetes. Cholesterol is perhaps the most successful and horrific redefining of normal that the medical world has ever got away with. Here is a graph of a normal distribution for cholesterol in the UK. The most common reading is 5.5-5.9. The normal distribution in this case is not as symmetrical as the diabetes curve. This one is what we call a “skewed distribution”. There are four groups below the most common group and eight groups above. This graph tells us that a cholesterol reading of 3.5-3.9 is normal, if uncommon and a cholesterol reading of 9.5-9.9 is also normal, if uncommon. Can you imagine the reaction of your doctor if your cholesterol reading were 9.5?! And yet it is absolutely normal that a section of the population will have this as their normal reading.
Just as happened with diabetes, normal is not allowed to remain normal. The medical profession has redefined cholesterol to be high at the absurdly low number of 5. You can see from the graph that only a small proportion of the population would have a cholesterol level below 5 in normal circumstances. Indeed, if you look at government data measuring people against this made-up target – the Health Survey for England for example (summary of key findings) - we have the crazy situation (page 22) where it is noted that 80% of men and women in many age groups have cholesterol levels above the government target of 5.0 mmol/L. That’s not because 80% of people have ‘high cholesterol’, but because normal has been redefined as high so people cannot be normal any more.
You know why this happens. Normal people have no value whatsoever to the pharmaceutical industry. But redefine ‘normal’ as high and suddenly healthy people can be medicated. This is how Lipitor was able to earn $125 billion for Pfizer during its patent. And who sets the targets?
In America, they are set by the National Cholesterol Education Programme (NCEP). The 2004 NCEP financial disclosure report reveals that ALL members of the 2004 guideline participants had received payments and/or grant funds from some, many or most of the following organisations: Abbott, Astra Zeneca, Bayer, BMS-Sanofi, Bristol-Myers Squibb, Esperion, Fournier, Glaxo SmithKline, Kos, Lipid Sciences, Merck, Novartis, Pfizer, Procter & Gamble, Reliant, Sankyo, Takeda, Tularik, Wyeth. (For full details of conflicts see point 3 on this post.)
In the UK they are set by the National Institute of Clinical Excellence (NICE). Here are their conflicts - 8 out of 12 of the NICE panel members have conflicts of interest with the statinators.
Blood pressure is the same. Here is a journal article with a couple of very interesting graphs – open up figure 1 and figure 2. Figure 1 is the higher number when you have your blood pressure reading (the 140 in 140/90 kind of thing). This shows that the normal blood pressure range for the general population is anywhere from 90 to 240 as the top number, with 130 being the most common reading (mode) and the average (mean) being around 140.
Figure 2 is the lower number (the 90 in the 140/90) and this ranges from 50 to 130. The most common is around 85 and the average is around 90. So the true average blood pressure (BP) in the normal population is approximately 140/90. You may be aware that 140/90 is the definition of high BP. Yet again, normal has become high and now everyone who is deemed high shall be medicated, when they are in fact normal.
Height and foot size
In the Western Journal of Medicine, (May 2002) Thomas Samaras and Harold Elrick posed the question “Height, body size and longevity – is smaller better for the human body?” The study took 100,000 males from 6 different ethnic populations – in the same city (California) to try to normalise other factors. The table had the following height orders (tallest first): African Americans; White Americans; Hispanics; Asian Indians; Chinese and Japanese (the first two groups were recorded as of equal average height – 70 inches).
The death rates for all causes and coronary heart disease (CHD) were presented in the study. A clear pattern was immediately obvious. I calculated the correlation coefficients as 0.85 for height and CHD and 0.9 for height and all causes of death (1 is a perfect relationship – scores of 0.85 and 0.9 are very strong relationships).
What if we concluded that height were a cause of CHD (and all causes of death) and that we should therefore redefine the average height to declare the actual average of 69.7 inches (for all American men) to be abnormal? What if we made up a new target 10% lower than the actual average and decreed that normal height should be 63 inches? We could then administer drugs to stop growth hormones from doing their job. I trust that this analogy disturbs you and yet…
The Chinese practice of foot binding – an artificial intervention in the normal development of the human body, to achieve an artificial ‘norm’ – was thankfully outlawed in the early twentieth century, but trying to reduce many other genuine human norms – from diabetes to BP – has now become common practice and big business.
Last week something quite extraordinary happened in the UK medical world. The National Institute of Health and Clinical Excellence (NICE) describes itself as follows: “We provide independent, authoritative and evidence-based guidance on the most effective ways to prevent, diagnose and treat disease and ill health, reducing inequalities and variation.”
Overnight on June 10th 2014, an open letter was sent to NICE and the Health Secretary, Jeremy Hunt, and a press release was issued by a group of doctors and academics. The letter essentially said to NICE – you are not independent and you are not evidence based and we call on you to withdraw the latest guidelines on statins until the drug company funded ‘researchers’ conducting trials and withholding vital data are forced to share that data.
This is the letter that was sent. This is the press release .
The points made by the doctors and academics
To summarise the six subheadings in the letter, the authors questioned:
1) Whether five million more healthy individuals should be medicated.
2) How could vastly conflicting information on side effects be explained (we’ll come back to this one).
3) How can it be right that the Cholesterol Treatment Trialists (CTT) Collaboration have commercial agreements with drug companies, which seem to exempt them from sharing what doesn’t suit their paymasters.
4) Why is NICE relying upon trials funded by drug companies when evidence shows (unsurprisingly) that these will find in favour of their drug. The open letter included the conclusion of the one major non-industry funded trial on statins (ALLHAT-LLP). This lone independent study found “No benefit was demonstrated in ALLHAT-LLT, the largest clinical event trial of pravastatin published to date.”
The open letter made two final damning points – the first reminding NICE that it is not considering all data because data is being withheld – and the collective view of GPs on this:
5) A recent meeting of the General Practitioners Committee (GPC), which represents GPs, passed a resolution requesting that NICE refrain from issuing its statin recommendations until there is complete disclosure of all clinical trial data.
The second, bringing into question the claimed independence of NICE:
6) We have serious concerns that 8 out of 12 people on the NICE statin guidelines committee have ties to the drug companies (I shared the conflicts here soon after the guidelines were issued). We have serious concerns about NICE’s reliance upon the CTT/Clinical Trials Service Unit (CTSU) drug company funded trials. e.g. the REVEAL study for which the CTSU received £96 million in funding from Merck Sharp & Dohme.
It is difficult to describe just how extraordinary this turn of events has been in the world of the statin/cholesterol debate. I highly recommend reading the letter and press release in full (there’s some classic Dr Malcolm Kendrick humour in the press release) if you’re interested in the world of health/drugs and doctors. This has been a seminal moment in the doctor/guidelines relationship.
There was some more humour in Dr Malcolm’s appearance on BBC breakfast when statin side effects were being discussed: “Statins will add 15 years to your life – they won’t make you live 15 years longer; they’ll just make you feel 15 years older!”
Statin side effects
You may be aware from this post that there is a debate going on about the true extent of statin side effects. This has become a much discussed issue after Professor Rory Collins demanded that the BMJ remove two articles, which referenced a peer reviewed paper that estimated the side effects of statins to be approximately 20%. Dr David Newman has rightly called this “An assault on science“. I’m in possession of a document showing that the true extent of the pharma funding for the CTSU is £250 MILLION. This is not just an assault on science, it’s an absolute disgrace that a Sir/Professor/Lord-high-executioner can make demands in this way from the worst position of conflict I have ever seen.
The open letter to NICE/Jeremy Hunt presents some inexplicable data. Under subheading 2 (conflicting levels of adverse events), the letter notes that the LIPID trial reported total adverse effects [side effects] as 3.2% for pravastatin and 2.7% for the placebo. The METEOR trial reported total adverse effects as 83.3% rosuvastatin and 80.4% for the placebo. There were six other trials listed (falling between 2.7% and 80.4% in side effect rates) and yet the placebo and statin adverse effects were almost identical every time. This raises two questions, which the open letter has invited NICE to explain:
i) How can there be a thirty fold difference in side effects from statins (80% over 2.7%)?
ii) How can the placebo be virtually the same as the statin in every trial – whether or not the statin results in 2.7% side effects or 80%?
I can’t explain this. Jerome Burne can’t either. Here’s my best guess – the data has been manipulated to ensure whatever side effects were reported in the statin victims, the placebo arm looks the same. I’m open to other suggestions.
This part of the letter alone also makes a mockery of Collins’ claim that you’ll see side effects in barely 1 in 100 cases. If we average the eight trials, side effects in the statin takers were 19.8%. Oh look – just like the 20% in the Zhang et al paper, referenced by Dr Aseem Malhotra and Dr John Abramson.
The NICE reply
The NICE response was almost as extraordinary as the open letter. The NICE response was posted on the same day that the letter was issued (10th June). I appreciate that they would have had advance notice before the open letter was issued, but they still don’t appear to have devoted much time to a considered response.
The NICE response opened by quoting its own Professor Mark Baker, Director of the Centre for Clinical Practice at NICE: “Cardiovascular disease maims and kills people through coronary heart disease, peripheral arterial disease and stroke. Together, these kill 1 in 3 of us. Our proposals are intended to prevent many lives being destroyed.”
I heard Mark Baker saying that exact comment on Sky news interviews and almost fell off the sofa. That’s emotive, scare-mongering worthy of a Hollywood trailer – not a public health body trying to be taken seriously.
Here are the facts on your chance of dying from heart disease. You would have needed to know 3,030 men (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. You would have needed to know 12,500 women (under the age of 65) for 1 of them to have been likely to die from heart disease during 2009. (Double these odds if you like, to capture the broader concept of cardiovascular disease rather than heart disease. I’d still need over 6,000 female friends under 65 to be attending one of their funerals from CVD).
We have to die of something. Arguably we all die of heart disease because death is confirmed when the heart stops beating. Cancer is just about the only other major thing that claims a place on death certificates. So yes, one in three of us have the likelihood that cardiovascular disease will be on our death certificate. The chance of that happening is so massively related to age that we should worry way more about birthdays than we do anything else.
The second astonishing approach taken by NICE was to present no defence whatsoever of the “8 out of 12 statin committee members prefer drug money” allegation. Paragraph four opens with “The independent committee of experts found…”. Paragraph five opens with “NICE guidance is developed by independent expert committees…”
Dear NICE – simply repeating that you’re independent does not make you so.
NICE has this to say: “They [independent expert committees] review all of the available evidence …” Yes – but what are you doing about the unavailable evidence? The evidence deliberately being withheld? If the CTT/CTSU have commercial arrangements, which ‘exempt’ them from sharing inconvenient data, why do you, NICE, not reject every study that they publish until they do fully disclose serious adverse effects and other information that they refuse to share.
The open letter recommends that the Cochrane group (the group set up to be genuinely free from big pharma) be allowed to scrutinize the CTT/CTSU data. It is just incomprehensible that NICE don’t seem bothered that they have 8 out of 12 fat cats dealing with biased pharma controlled data.
Mark Baker’s other ‘fall on the floor’ comment was along the lines of “because the price of statins has fallen [they’re off patent now], we can afford to give them to more people”. Smarties are fairly cheap – it doesn’t mean that we should hand them out to everyone. What happened to first do no harm? What happened to leaving healthy people alone? What happened to truly understanding the side effects of a drug before assuming them to be as safe (or as harmful) as Smarties?
This rationale for statins also illustrates the naivety (or even more sinister conflict) of NICE. There were similarly naive (or conflicted) comments on newspaper websites: “statins don’t cost as much now – so why not dish them out?” Apart from the harm, here’s why…
As the open letter explains in subheading 6, people like Dr Malcolm Kendrick and Dr Aseem Malhotra, who work with true independence in the statin world of reward, are aware of where statins are going next. When a drug as lucrative as statins ($125 BILLION for Lipitor alone) is approaching the end of its patent, you can bet that the replacement is being worked on in haste. And it is. And it will come in the form of PCSK9 inhibitors. And the chair of the NICE guidelines panel just so happens to be the lead UK investigator for the Pfizer RN-316 (anti-PCSK9 antibody) programme and the site investigator AMG-145 (anti-PCSK9 antibody) Osler lipids follow-on study. Oh and guidelines panel member Michael Khan just happens to be on the advisory board for Amgen for PCSK9 and he’s doing a clinical trial for Amgen on PCSK9. Oh and Emma McGowan is also doing a PCSK9 clinical trial. Oh and Dr Alan Rees (Mr Heart UK) is advising Sanofi AND Aegerion AND Amgen on PCSK9 and getting honorarium payments, speaker fees – no payment details shared. Mr Heart UK is also principal investigator on two PCSK9 trials. It’s all here – Appendix B - runs for 20 pages.
So – is the NICE panel naive to not realise the PCSK9 game being played or corrupt?
We are currently in that vital window for drug companies where they have a unique opportunity to expand a market in preparation for the next drug-of-riches-beyond-wild-dreams. This is what is happening right now. If only five million more adults (in the UK alone – more in US, Australia, NZ, Europe etc) could be put on these ‘cheap’, off-patent statins, when ‘son of statins’ (as Dr Malcolm calls PCSK9 inhibitors) are introduced, doctors will be deemed reckless if they do not move all their statin patients to the ‘new and improved’ medication. The ‘new and improved’ medication that will be able to return even more than statins Mark I having just expanded the client base. If you’re interested in learning more about PCSK9 inhibitors, you may enjoy this and this and this.
Where are we now
We end the week commencing 9th June 2014 with NICE badly wounded. They would not take a cheap swipe in their response at …”the American doctor, who co-signed the letter…” if they were not hurting.
I wrote to Health Secretary, Jeremy Hunt, on 17th February 2014 about the NICE conflicts of interest and he left it to NICE to reply. It will be interesting to see if the Health Secretary replies to this open letter, or if the NICE immediate response is all that we will get.
The February “extend the use of statin” guidelines from NICE have been out to consultation since then and final recommendations are due to be published next month. It will be interesting to see what final position NICE adopts. We may then have the unprecedented situation where GPs are openly rejecting guidelines issued by their advisory body.
The comments sections under media articles and even the BMJ rapid responses alongside Fiona Godlee’s editorial are littered with stories from individuals sharing their own statin experiences. The diabetes statin lawsuit continues in the US – women seem to be particularly badly affected – as the open letter to NICE detailed. The Collins “Assault on Science” has at least opened up awareness of statin side effects and angry people are sharing their unpleasant and disabling experiences.
Meanwhile the drug companies are really not bothered. Even if Collins is forced to declare the full extent of side effects and release raw data, so that people like me can have some fun with it, it will be too late. The only question now is – how many people will be on “son of statins” – the millions who are on statins now or five million more? It would be like you or me winning £109 million or £115 million on the lottery – would it really matter?
This is extracted from: “The Obesity Epidemic: What caused it? How can we stop it?”
During June and July of 2009 I approached the British Dietetic Association (BDA), Dietitians in Obesity Management (DOM), the National Health Service (NHS), the National Institute for Clinical Excellence (NICE), the Department of Health (DoH), the National Obesity Forum (NOF) and the Association for the Study of Obesity (ASO) to ask all of these expert organisations for proof of the 3,500 formula (also known as the calorie theory).
British Dietetic Association (BDA)
On 10 June, I sent the following query to the BDA: “I am doing some research on obesity and I would be most grateful if you could help me. Please can you explain where the ‘One pound of fat contains 3,500 calories…’ comes from?”
I received a prompt and pleasant reply, “Unfortunately we do not hold information on the topic that you have requested.” It was suggested that I contact a dietitian. I happened to be with several dietitians at an obesity conference later that month, so I asked fellow delegates and no one knew where the 3,500 formula came from. No one knew where the ‘eatwell’ plate proportions came from. One dietitian said to me “You’ve made us think how much we were just ‘told’ during our training, with no explanation. A group of us over there don’t even know where the five-a-day comes from.” (This may help)
So, after the conference, on 29 June, I sent the following email to the NHS: “I am an obesity researcher and I am trying to find out the rationale behind the statement: “One pound of fat contains 3,500 calories, so to lose 1lb a week you need a deficit of 500 calories a day”. This specific reference is a verbatim quotation from the British Dietetic Association’s Weight Loss Leaflet Want to Lose Weight and keep it off? The BDA reply was ‘we do not hold information on the topic.’ As this formula is the foundation of all current weight loss advice, it is critical to be able to prove it. Please can you let me know where this formula comes from and the evidence for it?”
On 30 June I received another prompt reply: “Unfortunately our Lifestyles team do not hold this information and are unable to assist you with your enquiry. I would suggest you contact the Department of Health to see if they can help.”
On 1 July I forwarded the email exchange with the NHS to the Department of Health. I had to chase on 6 July and then got a response saying they would get back to me within 20 working days. Meanwhile, I had also written to NICE (1 July) and they responded on 2 July saying they would get back to me within a maximum of 20 working days.
National Obesity Forum (NOF)
On 2 July I sent the same email to the NOF and the ASO and received a very prompt email back from the NOF (two hours later) suggesting that I contact the ASO. I thanked the NOF for this, but pointed out that their own web site quoted the 3,500 formula verbatim and also had the following classic example: “one less (sic) 50 calorie plain biscuit per day could help you lose 5lbs (2.3kg) in a year – and one extra biscuit means you could gain that in a year!” I have heard nothing back from the NOF since. I sent Dr. David Haslam, NOF chair, an email on 6 July attaching An Essay on Obesity, which I had written, for his interest and comment. On 10 July I also sent Dr. Haslam the exchange I had had with the ASO, so that information could be shared.
Association for the Study of Obesity (ASO)
The ASO response was the most helpful by far, but it still completely failed to prove the 3,500 formula. My query was circulated to board members and two kindly replied:
One reply was: ”Basic biology tells us that 1kg pure fat, converted to energy = 9000 kcal, 1lb pure fat = 0.453 kg = 4077 kcal. The approximation to 3500 kcal is made on the basis that ‘adipose tissue’ is not 100% fat (some water and some lean tissue). Hence to lose 1lb pure fat = 4077 kcal deficit, or 1lb fat tissue in the body = approx 3500kcal deficit. This equates to 500kcal per day to lose 1lb in a week. This has been supported by numerous studies using whole body calorimetry.” There were no sources put forward, for these “numerous studies”. I asked on 21 July and again on 11 August for “even one obesity study that proves this formula” and have received nothing back.
You can make 1lb = 2,843 calories or 3,752 calories without much effort. (This error could have a weight impact of a two stone loss or a six stone gain each year if any of this nonsense were true.)
The ASO member uses the word “approximation”, as do many references to the calorie formula, so there may be some acknowledgement of the number of variables. However, the diet advice that follows takes no account of this word “approximation”. If we take just one variation – the difference between 3,555 and 3,500 equates to five to six pounds a year. The NOF cautions that eating, or not eating, one biscuit a day could cause a person to gain, or lose, five pounds in a year. Well, the formula being inaccurate can also do this without any biscuit involvement at all. In fact, if 3,555 is correct and not 3,500 (notwithstanding the fact that there is no proof for either formula), this would have made a difference of 172 pounds over the past 30 years (the obesity epidemic period). Fortunately the error would be ‘in our favour’ so we should have all been able to eat nearly 11,000 biscuits and get away with it, or be over 12 stone lighter.
The second reply from the ASO was ‘evidence’ from NICE and a web link to the full NICE document Management of obesity: Full Guidance, December 2006. The specific proof offered was one study (Table 15.14) of 12 subjects, given a deficit of 600 calories a day, where the outcome was “a change of approximately -5 kg (95% CI -5.86kg to -4.75kg, range -0.40 kg to -7.80 kg) compared with usual care at 12 months. Median weight change across all studies was approximately -4.6 kg (range -0.60 kg to -7.20 kg) for a 600 kcal deficit diet or low-fat diet and +0.60 kg (range +2.40 kg to -1.30kg) for usual care”.
So, let me understand this, the people on the 600 calorie-a-day deficit (the NICE recommendation) were 5 kilograms (11 pounds) lighter than those not doing this “at 12 months.” Applying the basic maths formula, these 12 people should each have lost 600*365/3,500 = 62.57 pounds of fat. Not an ounce (of fat) more or less. AND, there should have been no range of results – everyone should have lost exactly the same (that’s what happens with a mathematical formula). The least anyone lost (let’s put it all into pounds) was 0.8 pounds and the most anyone lost was 17.2 pounds. Even the highest weight loss was 45 pounds lower than it should have been. This is also all about fat – we haven’t even started looking at muscle or water loss. This is also a study of 12 people. There are 1.1 billion overweight people in the world and we can’t prove a formula using 12 of them.
There were 15 other studies in Table 15.14, 10 of which had data for where a calorie deficit had been created over a specified period of time. This enabled me to analyse what the weight loss should have been (using the 3,500 formula) and what the average weight loss actually was (from the study data). Again, in every single study, there was a wide range of results (which means that the formula failed per se). In all of the other ten studies, the actual weight loss was multiples away from what the weight loss should have been. The smallest gap between actual weight loss and ‘should have happened’ weight loss (according to the formula) was 28.7 pounds (we continue to ignore water to try to give the formula a chance). At the other extreme, the biggest difference between the fat that should have been lost and the fat that was lost was 143.9 pounds.
Department of Health (DoH)
I was still digesting the immense implications of all this when the DoH reply arrived, on the 21 July, saying “The Department is unaware of the rationale behind the weight formula you refer to.” Pause for a second – the UK government Department of Health, has no idea where their founding piece of diet advice comes from. They kindly suggested another lead, (Dietitians in Obesity Management UK (DOM UK) – a specialist group of the British Dietetic Association), which I followed up on 24 July.
National Institute of Clinical Excellence (NICE)
I chased NICE on 27 July, as the 20 working days were ‘up’ in my calendar. I appeared to have been passed between NHS and NICE during July and a helpful woman called me back to say she had found the right department to deal with the query. A couple of days later, the reply came “Whilst our guidance does contain reference to studies involving 500 calorie deficit diets we do not hold any information about the rationale behind the statement ‘one pound of fat contains 3,500 calories, so to lose 1lb a week you need a deficit of 500 calories a day’.” That is to say – although we are an evidence based organisation, we have no evidence.
Dieticians in Obesity Management (DOM)
On 10 August I received a response from DOM UK: “I have asked our members and this answer was returned. It’s a mathematical equation, 1gram of fat is 9kcal, therefore 1kg fat equals 9000kcal. There are some losses but 1 lb of fat is approximately 4500kcal divide that by 7 days and its (sic) approximately 643kcal hence the deficit.” I went back to DOM UK, on the 10 August, to request an answer to the second part of the calorie theory – if that is how 600 calories is derived (and I have never before seen the 3,500 become 4,500), how can we then say with such confidence that each and every time this deficit is created one pound will be lost.
On the 18 August, I received a reply from one of the DOM UK Committee members: “My understanding is that it comes from the thermodynamics of nutrition, whereby one lb of fat is equivalent to 7000kcals, so to lose 1 lb of fat weight per week you would need an energy deficit of 7000kcals per week, or 500kcals a day. In or around that, depending on whether or not you use metric system and your clinical judgement, some people use a deficit of 600kcals a day and others 500kcals a day. There is good evidence that this level of deficit produces weight differences of approx 5kg at 1 year.”
This time the 3,500 deficit ‘needed’ has doubled to ‘7,000’ calories. Or, to put it another way, one pound of fat has become 7,000 calories. You can start to see what I have experienced as a researcher – how widely this formula is used as fact and yet how little it is understood and how few people know how to use their own ‘fact’.
So, in the example from Dietitians in Obesity Management, key proponents of the calorie formula, one year of a 600 calorie a day deficit will produce a weight loss of approximately 11 pounds – not the 62.5 pounds of fat alone that should be yielded.
When I pointed this out and suggested “I really think we need to fundamentally review the basis of current diet advice and stop saying ‘to lose 1lb of fat you need to create a deficit of 3500 calories’”, the final reply I got was “I guess a key to all of this is that weight loss doesn’t appear to be linear, any more than weight gain is.”
At last, an admission that the formula has no basis of fact.
The organisations approached have been helpful and accessible, but none is able to explain where the 3,500 comes from, let alone to provide evidence of its validity.
I have a simple and reasonable request. I would like proof of this formula – that it holds exactly every single time – or I would like it to be banished from all dietary advice worldwide.
Any proof needs to source the origin of the formula. Then the proof needs to hold in all cases. There needs to be overwhelming, irrefutable and consistent evidence that each and every time a deficit of 3,500 calories is created, one pound of fat is lost.
Since, we already have overwhelming evidence that such proof cannot be provided, it is not enough that we quietly stop using this formula – it is too widely assumed to be true for us to just sweep it under the carpet. We need to issue a public statement saying that it does not hold and should not be used again. We need to tell people that they will not lose one pound of fat for every deficit of 3,500 calories that they create. We need to tell people that there is no formula when it comes to weight loss and we have been wrong in giving people the hope that starvation will lead to the loss of 104 pounds each and every year, in fat alone.
You Magazine, Mail on Sunday (18 & 25/5/14), featured a new book by Ian Marber and Dr Laura Corr, with recipes by Dr Sarah Schenker, called “Eat your way to lower cholesterol: Recipes to reduce cholesterol by up to 20% in under 3 months”.
My first thought, upon seeing the title, was – why would anyone want to lower cholesterol? Sadly, this will be the last thought of most people browsing amazon or a book shop. Everyone nowadays wants to lower their cholesterol – that’s how successful the cholesterol lowering industry has been at demonising this life vital substance in the name of money.
Lowering cholesterol – General consensus vs. evidence
Stop 100 people in Queen Street, Cardiff, and 99 will tell you that cholesterol is bad and the lower one’s cholesterol level the better. Now may be a useful time to remind people of the true relationship between cholesterol and deaths. Scroll down the blog post until you see four graphs showing the following:
– The higher the cholesterol, the lower the deaths from CVD (cardiovascular disease) for men;
– The higher the cholesterol, the lower the deaths from CVD (cardiovascular disease) for women;
– The higher the cholesterol, the lower the deaths from any cause for men;
– The higher the cholesterol, the lower the deaths from any cause for women.
This is pure (not-played-with) data from the World Health Organisation for 192 countries. That’s just about as good as data gets and it shows the exact opposite of what we’re being told.
This is raw data – what about studies?
The Honolulu Study (Ref 1) was a 20 year study of cholesterol levels and mortality in 3,572 Japanese American men. The study concluded that “Only the group with low cholesterol concentration at both examinations had a significant association with mortality”. The authors added “We have been unable to explain our results”. (I.e. we were expecting lower cholesterol to equal lower mortality, not the other way round).
Framingham (the longest and probably best known population study ever) similarly concluded: “There is a direct association between falling cholesterollevels over the first 14 years and mortality over the following18 years (11% overall and 14% CVD death rate increase per 1mg/dL per year drop in cholesterol levels).” (Ref 2) Dr Malcolm Kendrick did a clever calculation on this finding and translated this into – a reduction in cholesterol from 5 to 4 mmol/L would increase your risk of dying by 400%.
Elaine Meilahn reported in Circulation (2005) “In 1990, an NIH (National Institutes of Health) conference concluded from a meta-analysis of 19 studies that men and, to a lesser extent, women with a total serum cholesterol level below 4.2 mmol/L exhibited about a 10% to 20% excess total mortality compared with those with a cholesterol level between 4.2 and 5.2 mmol/L.” (Ref 3)
Still want a book claiming to lower your cholesterol?
Lowering cholesterol through diet – how?
The 18/5/2014 You Magazine article has a box-out called “six superfoods” to boost heart health“. Notice how lowering cholesterol has already become interchangeable with heart health? Before you reach the end of this article you will see that there is no evidence whatsoever for that claim… quite the opposite in fact.
The six superfoods are claimed to be fibre; healthy oils (described as those high in unsaturated fat of course); soya; nuts; oats and ‘smart foods’. Smart foods are defined as margarine-like spreads and other fortified foods that claim to “actively lower you cholesterol” (those yoghurt/drink/one-a-day kind of things).
The only two of these six that I would describe as foods are nuts and oats. Fibre is a component part of carbohydrate (not all carbohydrates contain fibre, but no pure fat/protein contains fibre). ‘Smart foods’ are a category of processed gunge. Oils are nutritionally pointless and they’re a cooking ingredient/dressing, not a food. Soya is a whole different ballgame – see “The Whole Soy Story” by Dr Kaayla Daniel for the Whole Sorry Story on this one.
Which reminds me – please tell me that this book comes with the most obvious possible warning for any female wanting to conceive? Soya alone is a plant oestrogen – think ‘the pill’. It takes a lot of cholesterol to make a healthy baby and lowering cholesterol is the last thing that a would-be-mum wants to do. I’m not sure of the impact on male sperm either – almost certainly not good.
Replacing cholesterol more like
The key thing that this strange list of foods and non-foods have in common is (phyto)sterols. Sterols are added to margarines and other substances that have cholesterol lowering claims. You don’t need to consume these fake and expensive products. If you’re daft enough to want to lower your cholesterol you can buy sterol tablets from a health food shop and save yourself the harm and expense of ingesting spreads or ‘shots’.
Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations found in vegetable oils. They are absorbed only in trace amounts, but they inhibit the absorption of intestinal cholesterol (Ref 4) – human cholesterol in effect. We have known this for 60 years. The ability of phytosterols to inhibit the absorption of cholesterol was first shown in 1953 (Ref 5). (Fibre per se has a similar effect – it reduces the body’s absorption of cholesterol.)
Foods with phytosterols are competing with the cholesterol made by the human body and replacing it to an extent. Not entirely, or we’d drop dead. Blood cholesterol levels will fall, but how is this a good thing? Our bodies make cholesterol. I don’t know about you but I trust mine to make the cholesterol that it needs (so long as I don’t abuse it with statins). If my body needed plant cholesterol – surely it would make plant cholesterol? Do you know the true health impact of replacing your own cholesterol with plant cholesterol? Nope – me neither. And nor does Unilever I suspect.
The European Food Safety Authority responded to a request from Unilever PLC to be able to make cholesterol lowering claims on their plant sterol fortified products (Ref 6). The review body concluded that “plant sterols have been shown to lower/reduce blood cholesterol“. They also stated “However, there are no human intervention studies demonstrating that plant sterols reduce the risk of coronary heart disease.”
You may like to read that again (and You Magazine may like to retract their “boost heart health” claim). Plant sterols lower cholesterol (tick) but there is no evidence that plant sterols reduce the risk of heart disease. Can this mean that lowering cholesterol per se does not reduce the risk of heart disease? It sure does. However, there’s an even more important question to ask.
Is this even safe?
The area of most interest to us is phytosterol consumption and cardiovascular disease – as this is the area where health claims are made. There are a few studies of phytosterol intake and cardiovascular disease:
Rajaratnam et al studied the association of phytosterols and coronary artery disease (CAD) in postmenopausal women (Ref 7). They concluded that women with elevated ratios of sterols to cholesterol [i.e. plant cholesterol to human cholesterol] have enhanced risk for CAD. “Thus, enhanced absorption and reduced synthesis of cholesterol may be related to coronary atherosclerosis.” (My emphasis on enhanced risk).
Sudhop et al reviewed plant sterols as a potential risk factor for coronary heart disease (CHD) (Ref 8) and confirmed a strong influence of plant sterols. They concluded: “These findings support the hypothesis that plant sterols might be an additional risk factor for CHD.” (My emphasis on risk factor).
Assmann et al’s 2006 article concluded: “Elevations in sitosterol concentrations [one type of sterol] and the sitosterol/cholesterol ratio appear to be associated with an increased occurrence of major coronary events in men at high global risk of coronary heart disease.” (Ref 9) (My emphasis on increased occurrence of major coronary events).
Silbernagel et al studied 1,257 individuals in the Ludwigshafen Risk and Cardiovascular health (LURIC) study (Ref 10). They found that high absorption of phytosterols alongside low synthesis of cholesterol predicted increased all-cause and cardiovascular mortality in LURIC participants. (Naughty me again emphasising the finding that sterols replacing human cholesterol predicted dying.)
It has become so well known that ‘lowering cholesterol is a good thing’ that we are forgetting to challenge the entire and immense industry that has followed from this (drugs and spreads). Lowering cholesterol is a bad thing and replacing cholesterol with plant sterols is a very bad thing. These bad things are made even worse if the human being tampered with is of child bearing age/has parent-like aspirations. It’s also very bad for any human who wants to live longer. But, what the heck, so long as the cholesterol lowering industry is worth billions – who cares?!
1) Schatz, Masaki, Yano, Chen, Rodriguez and Curb, “Cholesterol and all-cause mortality in elderly people from the Honolulu heart programme”, The Lancet, (August 2001).
2) Anderson, Castelli and Levy, “Cholesterol and Mortality: 30 years of follow-up from the Framingham Study”, Journal of the American Medical Association (JAMA), (1987).
3) Elaine Meilahn, “Low serum cholesterol: Hazardous to health?” Circulation, (2005).
4) Ostlund, R. E., Jr. (2002) Phytosterols in human nutrition. Annu Rev Nutr. Vol.22 pp.533-49.
5) Pollak, O. J. (1953) Reduction of Blood Cholesterol in Man. Circulation. Vol.7(5), pp.702-706.
6) Bresson, J.-L. (2008) Scientific Opinion of the Panel on Dietetic Products Nutrition and Allergies on a request from Unilever PLC/NV on Plant Sterols and lower/reduced blood cholesterol, reduced the risk of (coronary) heart disease. The EFSA Journal. Vol.781 pp.1-12.
7) Rajaratnam, R. A., Gylling, H., and Miettinen, T. A. (2000) Independent association of serum squalene and noncholesterol sterols with coronary artery disease in postmenopausal women. J Am Coll Cardiol. Vol.35(5), pp.1185-91.
8) Sudhop, T., Gottwald, B. M., and von Bergmann, K. (2002) Serum plant sterols as a potential risk factor for coronary heart disease. Metabolism. Vol.51(12), pp.1519-21.
9) Assmann, G., Cullen, P., Erbey, J., Ramey, D. R., Kannenberg, F., and Schulte, H. (2006) Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study. Nutr Metab Cardiovasc Dis. Vol.16(1), pp.13-21.
10) Silbernagel, G., Fauler, G., Hoffmann, M. M., Lutjohann, D., Winkelmann, B. R., Boehm, B. O., and Marz, W. (2010) The associations of cholesterol metabolism and plasma plant sterols with all-cause and cardiovascular mortality. J Lipid Res. Vol.51(8), pp.2384-93.
Two very serious things happened last week – one in Australia and the other in the UK, although both are about information on line, so they have global impact…
Catalyst – Australia
Last October, two programmes aired on ABC television under the “Catalyst” banner (Catalyst is like Horizon – a science/investigation kind of programme). The first programme was called “Heart of the Matter Part 1 – Dietary Villains” and it aired on 24th October 2013. A transcript and copy has been preserved by someone on line. You can currently see it here, but I’m not sure for how long. The transcript of the programme is also available on this link. In essence – this programme challenged the widely held view that saturated fat causes heart disease.
The second programme aired on 31st October 2013 and, again, it can currently be seen here (video and transcript). This programme was called “Heart of the Matter Part 2 – Cholesterol drug war.”
Those who stand to gain from the diet-heart-cholesterol hypothesis did not want these programmes aired. There were calls for the second programme to be cancelled, after the first programme had been shown. The person making these demands, professor Emily Banks, admitted that she “didn’t have a lot of detail” about the cholesterol programme, but wanted it pulled anyway.
Both programmes aired. Catalyst is the only science show on Primetime Australian TV and it pulled in approximately 1.5 million viewers. That’s approximately half the number of people who take statins in Australia, by the way.
Barely had the closing credits run before the pro-statin brigade swung into action. A formal complaint was lodged with the body that reviews “Audience and consumer affairs” and a few months later, the findings were published in a 49 page document. In between airing and publication, Catalyst – producers and presenter (Maryanne Demasi) – were pretty much paralysed from doing further work by the demands placed upon them by the investigation.
You can read the full report. You may like to wait for a Dr Malcolm Kendrick blog – due any time now – where he summarises all the complaints made against the two programmes and those rejected and upheld. Nothing was upheld against the first programme on dietary fat and yet this has been pulled. For the second programme on cholesterol, I lost count of the judgements that recorded “no breach” of any of the codes – 16 I think. There was 1 breach upheld – and 1 alone. This is on P46 of the 49 page report.
The investigation concluded that in one part of one programme the presentation favoured an anti-statin view more than a pro-statin view. The report did not recommend that the programme be removed from the ABC web site and condemned to the scrap heap. You can see the recommended remedy on p4 of the report “We suggest it would be appropriate for additional material to be made available on the special ‘Heart of the Matter’ program website.” And that’s about it. Yet this programme has also been pulled – ABC have caved in to the pressure placed upon them by statinators. The intention of those who promote statins was no doubt to ensure that a programme like this is never aired, touched or conceived of again. They didn’t want this one to air. Tragically, they have almost certainly achieved their aim.
I tweeted the irony of the judgement – that the pro-statin bias prevails 365 days a year and yet 1 hour of a TV programme, where one small part was slightly less than balanced towards both pro and anti-statin views, is silenced – for bias! This isn’t about statins. It’s about censorship.
UK – BMJ
In the UK, in the same week, same drug, we also experienced censorship. Only this time, thanks to the robustness of BMJ editor-in-chief Fiona Godlee, we experienced only a small censorship – for now anyway.
On 15th May, Fiona Godlee published this editorial in the BMJ Godlee noted that, in October 2013, the BMJ “published an article by John Abramson and colleagues that questioned the evidence behind new proposals to extend the routine use of statins to people at low risk of cardiovascular disease. Abramson and colleagues set out to reanalyse data from the Cholesterol Treatment Trialists’ (CTT) Collaboration. Their contention was that the benefits of statins in low risk people were less than has been claimed and the risks greater.”
Godlee continued, “In their conclusion and in a summary box they said that side effects of statins occur in 18-20% of people. This figure was repeated in another article published in the same week in The BMJ by Dr Aseem Malhotra. The BMJ and the authors of both these articles have now been made aware that this figure is incorrect, and corrections have been published withdrawing these statements. The corrections explain that although the 18-20% figure was based on statements in the referenced observational study by Zhang and colleagues—which said that “the rate of reported statin-related events to statins was nearly 18%”. The BMJ articles did not reflect necessary caveats and did not take sufficient account of the uncontrolled nature of Zhang and colleagues’ data.”
Godlee had been alerted to ‘the error’ by Rory Collins, head of the Cholesterol Treatment Trialists (CTT) Collaboration, whose data were reanalysed by Abramson and colleagues. Godlee says in her editorial that Collins visited her at The BMJ in early December and then took the matter up in the UK media towards the end of March 2014.
The Guardian article references Collins as follows: “The Oxford academic said the side-effect claims were misleading and particularly damaging because they eroded public confidence. “We have really good data from over 100,000 people that show that the statins are very well tolerated. There are only one or two well-documented [problematic] side effects.” Myopathy, or muscle weakness, occurred in one in 10,000 people, he said, and there was a small increase in diabetes.”
The challenges that the Guardian should have made:
The Guardian should have ascertained how independent/conflicted their source was. These are the two pertinent questions:
1) How much, Professor Collins, have you/your department/your charity/your family – whatever outlets you have – received directly and/or indirectly from the pharmaceutical industry during your lifetime?
2) You head the CTT. Why will the CTT not release Serious Adverse Effect data (and raw data generally) from clinical trials so that researchers, doctors and patients can fully understand the side effects of statins? How can you claim that statin side effects are negligible when you won’t share the data?
The Guardian should have done their own (simple) research into statin side effects. Here are two pertinent questions:
1) If side effects are as rare as you say, why does the patient leaflet for Lipitor – the most lucrative statin, indeed the most lucrative drug ever in the history of mankind, state the following:
“Common side effects (may affect up to 1 in 10 people) include:
• inflammation of the nasal passages, pain in the throat, nose bleed
• allergic reactions
• increases in blood sugar levels (if you have diabetes continue careful monitoring of your blood sugar levels), increase in blood creatine kinase
• nausea, constipation, wind, indigestion, diarrhoea
• joint pain, muscle pain and back pain
• blood test results that show your liver function can become abnormal“
2) If diabetes is to be dismissed so lightly, why is the diabetes statins lawsuit gathering pace in the US? (Google diabetes statins lawsuit) and why is “increases in blood sugar levels” listed as one of the common side effects in the patient warning leaflet?
The web of funding around Collins, CTT, CTSU (Clinical Trial Service Unit) has proved astoundingly difficult to get to the bottom of. I had a bit of a breakthrough recently and came across a declaration of interest for Colin Baigent – CTT secretariat and close senior colleague of Collins. Check page five for current and recent grants. The following have been awarded to Colin Baigent and Rory Collins, (with other names mentioned alongside):
|Merck & Schering
||£39 MILLION (2002-2011)
||£52 MILLION (2005-2013)
|British Heart Foundation
||£9 MILLION (2005-2013) (Where does the BHF get that kind of money?) & then another grant from the BHF for £2.7 MILLION (2004-2013) & then a couple more for several hundreds of thousands of pounds.
|Medical Research Council
||£13.8 MILLION (2008-2013) (Check the most recent appointees to the MRC - a Senior Vice President of Pfizer and Executive Vice President of Astra Zeneca).
||A mere £965,000
|John Wyeth Ltd
That’s £116 MILLION before you get into the small change.
ABC has caved in, despite no judgement requiring them to do so. Godlee has asked a third party to review both articles to see if the current revisions are sufficient, or to decide if the two articles should be pulled. Collins wants both articles to be retracted. As Godlee points out: Malhotra’s article is primarily about saturated fat – it merely references the Zhang article, which Collins is not happy about and the Abramson article is primarily about the fact that the CTT data failed to show that statins reduced the overall risk of death in people with a <20% 10 year risk of cardiovascular disease. This is an important fact, which is important to be openly available.
I have no doubt that Collins would like these two articles deleted from the records forever. For him it may be about the statins that have funded him/his department/wherever to the tune of over one hundred million pounds. For the rest of us it’s about censorship.