118. Crony Capitalism. The Pharmaceutical Industry.

The use of drugs is an integral component of the conventional approach to modern medicine. Invariably a visit to your GP results in a prescription for at least one pill or potion. A similar treatment is often associated with a stay in hospital. The fundamental principle which underpins this strategy is that these medicines will be beneficial to the patient’s health. Furthermore while it is accepted that there may be side-effects, these can be tolerated if the benefits are genuinely worthwhile. The entire basis of the approach is dependent on regulatory processes that are rigorous in their assessments of the effects the drugs have on people who are treated.

Unfortunately a huge amount of evidence has emerged in recent years, which shows that there are serious deficiencies in the regulation of drugs and there are even suggestions that the process has been corrupted.

A recent book published in the US entitled “Crony Capitalism in America 2008-2012” (1) has a whole chapter devoted to the relationship between the pharmaceutical industry and the Food and drugs Administration (FDA). This has been reproduced on the Alliance for Natural Health website (2). This blog will focus on some of the key points. Although the book refers to the US many of the companies operate in the UK and it would not be in the least surprising if the relationship between the companies and the UK/EU regulatory authorities is essentially the same. Here are some of the hard realities of this business:

  1. Drug companies do not usually use natural compounds because it is impossible to patent them. As it costs somewhere around $billion to obtain approval, patenting is essential in order to recoup the costs involved.
  2. To facilitate approval process, the companies regularly hire staff with experience of working for the FDA. Many of the experts in the field who may be employed by universities and research organisations act as both advisers to the FDA and consultants to the industry.
  3. This engenders a cosy relationship between the both sides who participate in the regulation of the drugs
  4. According to a quote from the “Economist”:

Pharmaceutical companies bury clinical trials which show bad results for a drug and publish only those that show a benefit. The trials are often run on small numbers of unrepresentative patients, and the statistical analyses are massaged to give as rosy a picture as possible. Entire clinical trials are run not as trials at all, but as under-the-counter advertising campaigns designed to persuade doctors to prescribe a company’s drug.”

The “Economist” continues:

“Medical journals frequently fail to perform basic checks on the papers they print, so all sorts of sharp practice goes uncorrected. Many published studies are not written by the academics whose names they bear, but by commercial ghostwriters paid by drug firms. Doctors are bombarded with advertising encouraging them to prescribe certain drugs.”

5.       Knowledge of what is happening with respect to the progress of individual applications for approval can have major financial implications. An FDA chemist charged with criminal offences has pleaded guilty to leaking information about drug approvals or company mergers. Over a 5-year period the chemist had been involved with 25 companies and benefited to the tune of almost $4 million dollars.

6.       Once a drug has been approved it may be prescribed on a large scale, especially by official bodies such as the US government’s Medicare. Annual treatment costs for these approved drugs may be as high as $500,000 per patient. On the other hand, drugs which have not been approved are effectively banned in the US and doctors who prescribe them risk being stuck off and may even be prosecuted

7.       Although there may be compelling anecdotal evidence, including numerous case studies which indicate that naturally-occurring substances can be used successfully to treat a variety of diseases and conditions, the FDA insists that they can only be approved if the complete testing programme is implemented. Since there is no organization or company prepared to spend the money needed, there is no way that these substances will ever be approved. The position is re-inforced by the stance of the American Medical Association (AMA) which as a general rule is opposed to the use Complementary therapy but is also dependent on the pharmaceutical industry for much of its funding

8.       The use of generic drugs ought to be an effective means of reducing the costs of many drugs but this approach is to some extent stymied because the FDA insists that bioequivalence is demonstrated which adds to the costs. More significantly the FDA has a huge backlog of about 1900 applications for generics and the average time for a decision on approval is 26 months,

9.       In the US the government is very careful to avoid charging any leading pharmaceutical company with criminal misconduct. This is because conviction under the current law would mean that the government would no longer be able to purchase any products from that company. The government is too closely integrated with the drug/vaccine industry to allow that to happen. Thus, when Merck was found to have misled about its painkiller Vioxx, alleged to have caused at least 55,000 deaths (some estimates are much higher), the settlement with plaintiffs reached $4.9 billion. But Merck continued partnering with and selling to government without any interruption or even question.

This is just one example of crony capitalism in which government and industry become so interdependent on each other that there is really no effective control and the only beneficiaries are those individuals who have their “snout in the trough”. In essence the normal rules of competition are suspended and inefficiencies are rampant. It is of course the ordinary citizens who suffer because it is their taxes which are used to fund these excesses. They also miss out from the continued improvement in the quality of products coupled with a steady reduction in prices. As an example, compare the pharmaceutical industry with the mobile phone industry which advances in leaps and bounds. By contrast there is reliable evidence that there are very new drugs which actually perform significantly better than those already on the market and some which are worse, but no doubt are promoted as “wonderful”.

REFERENCES

  1. Hunter Lewis (2013) “Crony Capitalism in America 2008-2012” ISBN 978-09887627-2-7
  2. http://www.anh-usa.org/big-pharma-and-fda-a-marriage-not-made-in-heaven/

 

 

117. Statins: Email to Julian Smith MP

Good Morning Julian,

I have just posted this article on my blog at

http://vernerwheelock.com/?p=569   More details of the damaging effects of statins will be found at http://www.spacedoc.com/statin_side_effects

My primary concern is the fact that such a large number of perfectly healthy people are suffering serious ill-health even though NICE accepts that it will not improve their health in any way. I contend that this is totally unjustified and unacceptable.

The reality is that 100s of thousands (maybe even millions) of people are being damaged by statins when the vast majority  of them do not benefit in any way. There is no doubt that there is manipulation of the results conducted by the drug companies to play up the advantages and play down the undesirable side-effects of statins. (See http://vernerwheelock.com/?p=545  and http://vernerwheelock.com/?p=528)

This issue has all the hallmarks of other scandals which have come to light recently such as Rotherham, Stafford Hospital or Hillsborough. The only difference is that much larger numbers of people are involved. There is no doubt that NICE is a major part of the problem. I believe that for a start some of the parliamentary committees should conduct a detailed investigation into the role of NICE and its relationship with the drug companies. This email is a formal request to you to place this information with the Parliamentary Committees for Public Accounts, Science and Technology and Health in the hope that they will take appropriate action. Please take any other measure you think would be effective.

All the factual information is based on thoroughly reliable sources and I believe that this issue must be addressed sooner rather than later. Let us hope that this will not be another scandal that drags on and on for years because nobody in a position to act would listen !!!

A copy of this email is being sent to the Craven Herald and I will also be placing the information on my blog at http://vernerwheelock.com/

I look forward to hearing your response.

Very Best Wishes

Verner

 

116. Microchip to beat Obesity

According to The Guardian (8september 2014) Professor Sir Stephen Bloom is developing an “intelligent microchip” which will send signals to the brain that will stop the urge to eat. Bloom is head of the diabetes, endocrinology and metabolism at Imperial College London in Hammersmith Hospital. He believes that this will reduce appetite and therefore act as a means of overcoming obesity. In the interview Bloom says that obesity increases blood pressure and therefore increases the risk of having a stroke. He mentions that higher cholesterol means a person is more likely to have a heart attack, presumably also linked to obesity. Furthermore the incidence of Alzheimer’s Disease is one third higher in people who are obese. He goes on to state that most diabetes is caused by people being slightly overweight. So he concludes that if:

“….you could get rid of obesity, diabetes would fall to about a third or maybe a quarter”.

In my opinion Professor Bloom has made a number of assumptions in developing his strategy, which do not stand up to rigorous examination. As a consequence it is extremely doubtful if he can achieve his objectives.

First of all, if we consider those who are “overweight” as determined by BMI, we find that they actually have a greater life expectancy than those with a “normal” BMI, which is regarded as the ideal    (Table 1) (1). Although there is a small increase in the number of deaths due to kidney diseases and diabetes, this is more than offset by the reductions in deaths attributed to other causes.While it is true that those who are in the “obese” category have higher death rates, this only applies to those who are severely obese with a BMI >35 (2). Even then it is crucial to recognise this does not allow us to conclude that the cause is the excess weight.

TABLE 1 RELATIONSHIP BETWEEN BMI AND EXCESS DEATHS (1000s)

                                                                 BMI
Cause of death <18.5 18.5-25 25-30 >30
Coronary heart disease +3 0 -12 +6
Other   cardiovascular +8 0 -5 +36
Lung   cancer 0 0 -10 -7
Obesity   related cancer 0 0 -3 +20
All   other cancers +3 0 +3 +2
Diabetes/kidney   disease 0 0 +15 +34
Chronic   respiratory +16 0 -30 -6
Acute   respiratory/infectious +8 0 -8 -3
Injury +2 0 -32 -13
Other   causes +6 0 -52 +13
ALL +46 0 -134 +82

 

The nutrition literature is littered with examples of confusing cause and effect, which can be simply illustrated by this example. In an area of high crime it is likely that there will be frequent observations of police cars, while low crime localities will rarely have a visit from a police car. This does not mean that the police cars are the cause of the crime rate and it certainly does not follow that crime will be reduced if police cars are kept away!

We really do need to be much more critical in our thinking. It could well be that diabetes is one cause of obesity. However the most likely explanation is that there is a common cause for both. Our main concern is diabetes Type2 (T2D). This is raised blood glucose which stimulates the production of insulin by the pancreas. The insulin directs the glucose to the liver where it is converted into fat and then stored, which can ultimately result in obesity. The high levels of insulin in the body damage many of the organs, which can lead to heart disease and cancers. The obvious answer is to reduce the amount of glucose coming into the blood by cutting back on the consumption of sugar and refined carbohydrates.

There is a growing volume of evidence that this approach can overcome T2D (3,4,5). Invariably those who successfully reduce their blood glucose also find that they lose weight and the risk factors for heart disease are also lowered.

By contrast, the results for those who focus on weight loss alone are not encouraging. For example, in the Honolulu Heart Study, 6537 Japanese-American men aged 45 to 68 in 1965 and living in Hawaii, were monitored from 1973 to 1988 during which time there were 1217 deaths. The results are shown in Table 2. It is quite clear that there has been a notable increase in the death rate of those who lost weight. On the other hand, those who gained up to 4.5kg had a reduced death rate while those who gained more than that did not experience any increase in mortality rate when compared with those whose weight did not vary (6). Similar results have been observed in other investigations (7).

TABLE 2 RELATIVE DEATHS AND CHANGE IN BODY WEIGHT

  ALL-CAUSE MORTALITY  RELATIVE   RISK
Weight loss >4.5 kg 1.21
Weight loss 2.6-4.5 kg 1.29
No change 1.00
Weight gain 2.5-4.5 kg 0.83
Weight gain >4.5 kg 0.99

 

The hard reality is that T2D is not confined to those who are overweight or obese. A recent study conducted in the USA compared the death rates between those with T2D who were normal weight (BMI 18.5-25) and those who were overweight and obese (BMI>25). It was found that the death rates for those with normal weight was more than double that of those who were in the heavier categories (8). This paper also noted that overweight and obese patients with end-stage renal disease have better health outcomes than those who are lean. Furthermore, lean people with raised blood pressure and those with heart failure have worse health outcomes than their heavier counterparts.

So any strategy which focuses on weight loss per se is unlikely to be effective and may well do more harm than good. In addition, many diabetics are not overweight so weight loss is clearly not the solution.

CONCLUSION

It is virtually certain that this project is doomed to failure. There is ample evidence to demonstrate that weight loss by calorie control is very difficult to achieve and even when successful is rarely maintained. Even then, the chances are that there will not be any benefit to health. The real danger is that it diverts attention from the methods that are effective, especially making changes to food consumption patterns by limiting sugar and refined carbohydrates.

REFERENCES

  1. http://jama.jamanetwork.com/article.aspx?articleid=209359
  2. http://vernerwheelock.com/?p=132
  3. http://vernerwheelock.com/?p=226
  4. http://vernerwheelock.com/?p=405
  5. http://vernerwheelock.com/?p=422
  6. http://www.nejm.org/doi/full/10.1056/NEJM199509143331102
  7. http://vernerwheelock.com/?p=221
  8. http://jama.jamanetwork.com/article.aspx?articleid=1309174

 

 

 

 

 

115.Statins: Another Scandal in the Making

The latest edict from the National Institute for Clinical and Health Excellence (NICE) means that virtually everyone over 50 will be recommended to go on statins. NICE recognises that 77 people will have to be treated with these drugs over a 3-year period for one person to derive any benefit (1). It is crucial to understand that most of these are individuals who are perfectly healthy: the rationale for extending the scope of those being treated is prevention rather than cure. NICE also rejects claims that there are adverse side-effects when statins are used.

It really is unbelievable that NICE should be taking this stance when the benefits are so absolutely minimal. The organisation must be living in cloud cuckoo land if it considers this decision to be reasonable and logical. If people were informed there was only one chance in 77 that they would benefit I have no doubt that that the vast majority would not agree to the treatment and that is before any consideration of side-effects. In answer to a question, a spokesman justified statin use on the grounds that with blood pressure lowering drugs, only one in 104 would benefit!

A much more realistic picture was painted by a group of medical professionals led by Sir Richard Thompson, President of the Royal College of Physicians and Dr Clare Gerada, a former chair of the Royal College of GPs (2). In a letter to NICE, copied to Jeremy Hunt, they pointed out that:

  • There is  a lack of reliable evidence to demonstrate that when statins are used for primary prevention( ie. for people who have not had heart disease) there is any reduction in all-cause mortality
  • There is sound evidence that statins do cause adverse side-effects, which include muscle pain, cognitive impairment and erectile dysfunction. A study conducted in the USA with over 150,000 middle-aged women found that those on statins had a 48% increased risk of developing diabetes compared with those on a placebo
  • As 8 out of the 12 members of the NICE committee which made the recommendation on statins have financial links with the pharmaceutical companies producing the statins, there are genuine concerns about conflicts of interest
  • In a recent survey of 511 GPs conducted by the magazine Pulse, it was found that 57% oppose the plan to lower the current 10-year risk threshold for primary prevention from 20% to 10. Only 25% would support the proposals. It was also highly significant that 55% would not personally take a statin or recommend a family member to do so, based on a 10% risk.

An analysis of the results of trials to evaluate statins, shows that most of these studies have been conducted on men. Although there are fundamental differences between men and women in the way they respond to drugs, there is no convincing evidence that statins have any beneficial effect in women.

There is evidence that pressure has been applied by drug company interests to influence the results of a Cochrane Collaboration report in order to favour the use of statins (3).

It is clear that there is a very convincing prime face case that NICE is “not fit for purpose”. In particular, there is genuine concern that it is dominated by the interests of the pharmaceutical industry. Hence drugs are being recommended which have minimal benefit and therefore public money is being wasted on drugs that are ineffective. Even worse, some patients experience side effects which are not only unpleasant but can also cause serious damage to their health.

All the indications are that this is a major scandal which ought to be tackled sooner rather than later. Recent issues including Stafford Hospital, Hillsborough and Rotherham demonstrate the inertia of the authorities to take action despite numerous warning signs. There is not the slightest doubt that there is a pressing need to examine the role of NICE and its relationship with the drug industry simply because of the evidence that I have cited here. Ideally the Ministerial team at the Department of Health should act but they are probably incapable of dealing with the modern day Sir Humphreys. However these issues could well be tackled by Parliamentary Committees, which have the power to summon witnesses and cross-examine them. I would envisage that these topics would be ideal for the Public Accounts Committee, the Health Committee and the Science and Technology Committee. It would be fascinating to watch any attempt to justify the use of stains when the number to benefit is so small. Up to now these committees have been quick to jump into action once an issue has hit the headlines. However it would certainly be preferable if they did not have to wait to be prompted from outside sources.

Recently the Parliamentary Committee on Science and Technology expressed concern about the lack of transparency of the detailed results of clinical trials conducted by pharmaceutical companies to determine the effectiveness of drugs (4). In the absence of all the available original data it is not possible to make an accurate assessment of the effectiveness of any particular drug. The full implications of this have been spelled out in a recent book by Peter Gøtzsche (5). In this he describes how Pfizer had been fined $2.3 billion in the United States for promoting off label use of four drugs, while Merck had been responsible for the deaths of thousands of patients with its deceptive behaviour around a drug for arthritis.

I will be making this information available to the various Committees in the hope that this issue will be placed on their agendas. I also intend to forward this to my MP with a request that he presses for action and I hope that other readers in the UK will also pass on to their own MP.

At the very least I would expect that all information on the odds of success and the risks of adverse side-effects should be accessible to each and every patient before agreeing to treatment with any drug. If this episode is anything to go by, I suspect that most people would be very surprised at what they learn!

REFERENCES

  1. http://www.bmj.com/content/349/bmj.g4694
  2. http://www.nice.org.uk/media/877/AC/NICE_statin_letter.pdf
  3. http://vernerwheelock.com/?p=545
  4. http://www.publications.parliament.uk/pa/cm201213/cmselect/cmsctech/writev/clinicaltrials/clinicaltrials.pdf
  5. Peter Gøtzsche(2013). “Deadly Medicines and Organised Crime: How Big Pharma Has Corrupted Healthcare Radcliffe Publishing London

114. Potential Breakthrough in South Africa

There is now overwhelming evidence that the decision to advise consumers to reduce the amount of fat and saturated fat (SFA) in the diet has turned out to be one of the most disastrous mistakes in the history of public health policy. As people implemented the recommendations it was inevitable that there was a corresponding increase in the intake of sugar and carbohydrates. This was driven by the promotion of “low fat” products, many of which were formulated by replacing the fat with sugar. In addition, there has been a phenomenal growth in the sales of soft drinks, which usually have a very high content of sugar. The changes in food consumption patterns have been accompanied by increases in the incidence of obesity, although this has tailed off a bit recently in the UK. Even more seriously, diabetes is now a major problem. Here in the UK the incidence has doubled in the past 15 years and it is expected to continue increasing. Diabetes is especially worrying because it is associate with increased risk of heart disease, cancer and Alzheimer’s Disease. The NHS in England currently spends almost £1Billion on drugs to treat diabetics, while the cost of all treatment is about £10 Billion. It is reaching the point where it is becoming unsustainable.

The solution is blindingly obvious. The cause has to be removed. Diabetes is caused by excessive levels of glucose in the blood. If the amount of sugar and starch, which is broken down to glucose, is restricted in the diet then it follows that there will be less available for absorption from the gut into the blood. The logic is irrefutable. This is fully supported by reliable scientific research and a huge number of personal case histories from individuals who have reduced their intake of sugar and refined carbohydrates. It should also be appreciated that most of this can be replaced by fats, especially the SFAs, which are valuable nutrients in their own right (1). For more details of current thinking on nutrition I can recommend “the Diet Delusion” (2) by Gary Taubes and “Big Fat Surprise” by Nina Teicholz (3).

The big hurdle is that the majority of those in the medical and public health professions are not prepared to accept this relatively “new” understanding and interpretation. The fundamental issue is that most of those in a position to initiate a U-turn have been active proponents of the existing policies which have failed so miserably. There are probably several reasons for this.

  • They have closed minds and simply cannot adjust their thinking. As a result they perform all sorts of contortions in rather pathetic attempts to justify the status quo
  • They choose to ignore the new information and the consequences
  • They just cannot face up to the fact that they have been wrong in the past and therefore presented patients and governments with advice that was faulty.

There are also very powerful business interests, including food, pharmaceuticals and weight loss which would be adversely affected if there was a big shift in policy.

At present there is little doubt that the reactionary forces hold the upper hand simply because virtually all politicians are not prepared to challenge the relevant “experts”. This may seem bizarre but it does appear they lack the ability and the confidence to do so.

However the hard reality is that we are largely dependent on the politicians to initiate action. This is why we need to watch developments in South Africa very carefully indeed.

The story starts with Professor Tim Noakes, Professor of Sports Medicine at the University of Cape Town (UCT). For most of his life he had followed the conventional dietary guidelines. He was also very active as he went running most days and had competed in over 70 marathons and ultramarathons. About 4 years ago he started to question the rationale behind the dietary he was following and promulgating to others. As a consequence he decided that the advice was fundamentally flawed and so he went through the painful process of changing his mind. His current position is explained in an interview (4). He explains the rationale in a lecture given in 2012 (5).

Within the last few weeks Tim Noakes was invited to address members of the South African Parliament , where he obviously made a significant impact(6). As a result there is already an initiative to implement some of the proposals suggested. This really is a very big step forward and it is to be hoped that sooner rather than later, there will be moves to re-formulate the public health policies in order to alter the national patterns of food consumption.

However it will not be plain sailing because there has been a backlash from other academics in UCT, who wrote a letter which condemning the stance taken by Noakes. It was signed by Prof Wim de Villiers Dean of Faculty of Health Sciences, Prof Bongani Mayosi, Head of Department of Medicine, and emeritus professor, cardiologist Dr Lionel Opie, and Dr Marjanne Senekal, associate professor and Head of Division of Human Nutrition.

Here is the letter in full:

“The apparent endorsement by Members of Parliament of South Africa of the latest fashionable diet, ‘Banting’ (‘SA’s Ticking Time-bomb’, Cape Times, 19 August 2014) and the message it sends out to the public about healthy eating, is cause for deep concern – not only regarding Parliament’s support for it as an evidenced-based ‘diet revolution’, but sadly, the long-term impact this may have on the health of the very people they have been elected to serve.

“Any diet for weight loss and maintenance should be safe and promote health in the long-term. Currently the long term safety and health benefits of low carbohydrate, high fat diets – such as Atkins, Paleo and South Beach, and in which Banting falls – are unproven, and in particular whether it is safe in pregnancy and childhood.

“Importantly, while the consumption of a low carbohydrate, high fat diet may lead to initial weight loss and associated health benefits – as indeed would a balanced weight loss diet – there is good reason for concern that this diet may rather result in nutritional deficiencies, increased risk for heart disease, diabetes mellitus, kidney problems, constipation, certain cancers and excessive iron stores in some individuals in the long term. Research leaves no doubt that healthy balanced eating is very important in reducing disease risk (see web page below dedicated to this debate).

“It is therefore a serious concern that Professor Timothy Noakes, a colleague respected for his research in sports science, is aggressively promoting this diet as a ‘revolution’, making outrageous unproven claims about disease prevention, and maligning the integrity and credibility of peers who criticise his diet for being evidence-deficient and not conforming to the tenets of good and responsible science. This goes against the University of Cape Town’s commitment to academic freedom as the prerequisite to fostering responsible and respectful intellectual debate and free enquiry.

” This is not the forum to debate details of diets, but to draw attention to the need for us to be pragmatic. Research in this field has proven time and again that the quest for lean and healthy bodies cannot be a quick-fix , ‘one- size-fits-all’ solution. The major challenge lies in establishing sustainable and healthy dietary and physical activity patterns to promote long term weight maintenance and health after weight loss, and includes addressing psychosocial, environmental and physiological factors.

“Our bodies need a range of nutrients sourced from a variety of food groups to survive. Diets like the Banting are, however, typically ‘one dimensional’ in focus. They promote increased intake of protein and fat containing foods at the expense of healthy carbohydrate containing foods, and focus on adherence to a limited food plan. Ignored are the other important factors impacting on health – like physical activity (the important of which we cannot emphasise enough), environmental factors, and individual health profiles.

“UCT’s Faculty of Health Sciences, a leading research institution in Africa, has a reputation for research excellence to uphold. Above all, our research must be socially responsible. We have therefore taken the unusual step of distancing ourselves from the proponents of this diet. To foster informed engagement of the issues related to the Diet debate, the Faculty has established a (page on its website) with material on this.”

And this is the reply:

For whatever reasons, the Faculty of Health Sciences of the University of Cape Town manages consistently to misrepresent my public message which is simply the following: a high carbohydrate diet is detrimental to the health of persons with insulin resistance whereas carbohydrate restriction in this group can be profoundly beneficial as it can reverse obesity and in some cases Type 2 diabetes mellitus, the two conditions that will ultimately bankrupt South African medical services unless we take appropriate preventive actions. This message first presented publicly in my book Challenging Beliefs in 2011, has never changed.

“It is also the message I presented to members of staff at Parliament a week ago.

“If that message is without scientific support, then the Faculty of Health Sciences has every right to cross the civil divide as it has now chosen; an action which, I suspect, is unprecedented in the history of the Faculty of Health Sciences and perhaps the history of the University of Cape Town. But if there is evidence for my position, then the Faculty is guilty of failing fully to inform its past and present science, medical and dietetics graduates in a manner appropriate for a Faculty that considers itself to be a world-leader.

” An outline of the scientific evidence for my position is presented in about 20 000 words in our book Real Meal Revolution. That work includes references to the most important scientific works (of an abundant literature) supporting my interpretation. For the Faculty of Health Sciences of the University of Cape Town consistently to deny that peer-reviewed evidence is a classic example of cognitive dissonance.”

CONCLUSION

In my opinion, the letter from the academics is totally unacceptable. To claim that that the ideas advocated by Noakes may:

“result in nutritional deficiencies, increased risk for heart disease, diabetes mellitus, kidney problems, constipation, certain cancers”

simply beggars belief. There is not a shred of evidence to support the statement. Similarly it is totally unjustified to accuse Noakes of

“outrageous unproven claims about disease prevention”.

If the authors of the report had bothered to examine the evidence, there is plenty. Wild unsubstantiated statements are the hallmarks of desperation.

There is a very little doubt that obesity, diabetes and related diseases have been caused by precisely the type of diet which the UCT academics support. The writers of the letter appear to be so committed to theories which have been totally discredited that are not prepared to consider any alternative. The fact is that they are advocating strategies which have been largely responsible for the current disaster in public health. They would do well to note the conclusion of Albert Einstein who defined insanity as doing the same thing over and over again and expecting a different result!

It is to be hoped that the South African politicians stick to their guns and adopt the Noakes approach to construct a completely new public health policy. This would undoubtedly produce enormous benefits for the country with huge improvements in the health of the population, which must pay off in the economy. There would also be savings in health expenditure.

Finally South Africa would establish itself as the world leader in health policy innovation, which ought to trigger similar initiatives in many other countries.

REFERENCES

  1. http://vernerwheelock.com/?p=155
  2. Gary Taubes (2007) “The Diet Delusion” Vermillion: London
  3. Nina Teicholz (2014) “The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet” Simon & Shuster New York
  4. http://www.biznews.com/health-biznews-com/2014/07/tim-noakes-makes-real-meal-critics-say-diet-dangerous/
  5. https://www.youtube.com/watch?v=5IYVIdztWWs#t=31
  6. http://www.iol.co.za/news/politics/sa-s-ticking-time-bomb-1.1737511

 

 

113. Can We Trust the Drug Companies?

The banking industry quite rightly suffers from public opprobrium because of its role in the financial crisis, manipulation of the bank rate and mis-selling of various products. By contrast the pharmaceutical industry is somewhat more highly regarded. Nevertheless recent examples of unethical behaviour indicate that the approach to business in this sector does not exactly embrace the highest principles of corporate social responsibility.

I have just discovered a website which provides reliable evidence on how this industry operates (1). In this blog I will refer to a number of issues which have arisen in recent years.

  • In an undercover investigation, initiated by a tip-off from a whistleblower, The Daily Telegraph discovered that pharmaceutical firms appear to have rigged the market in so-called “specials”. These are prescription drugs that are largely not covered by national NHS price regulations. Secret recordings by Telegraph reporters showed that sales representatives for drug firms offered to provide apparently falsified invoices allowing chemists to bill the NHS for sums far greater than they would spend. Hence the retailers would be able to send inflated invoices to the NHS, allowing them to pocket the difference. As a consequence it was estimated that hundreds of millions of pounds of public money has probably been wasted in recent years due to the practice (2).
  • In a Newsweek investigation, reporter Sharon Begley concludes that the framework of medical research is fundamentally flawed so that the wrong answers are being produced time and time again (3). According to John Ioannidis, who is in charge of the Prevention Research Center at Stanford University people are being hurt and dying because of false medical claims which are based faulty research.
  • In a recent blog I have described in detail how pressure was applied to the respected Cochrane Collaboration to influence the conclusions of an evaluation of statins (4). Two professors from the University of Oxford persuaded the compilers of the report to reach a conclusion favourable to statins, based on data produced by pharmaceutical companies, which was not open to independent scrutiny. Other evaluations have concluded that there is no net benefit from statins when used for primary prevention. Despite this NICE has made recommendations which effectively mean that everyone over 50 will be offered statins. Even NICE accepts that 77 people will have to treated in order that one will benefit! In the USA alone the expenditure on statins is more than $20 billion per year, much of which is probably unnecessary.
  • There are many examples of “breakthroughs” which turn out to worthless when subjected to further examination. Various studies which concluded that popular antidepressants work by altering brain chemistry have now been contradicted. A study done in 1996 which concluded that estrogen therapy reduces older women’s risk of Alzheimer’s was overturned in 2004.
  • Richard Smith, a former editor of the British Medical Journal (BMJ) is convinced that fraudulent research regularly appears in the 30,000 scientific journals currently published throughout the world. Furthermore even when fabricated or falsified research is discovered, journals rarely publish a retraction. Dr Smith is critical of the failure of scientific institutions, including universities, to discipline dodgy researchers even when alerted to problems by journals. Most cases are not publicised. Few countries have measures in place to ensure research is carried out ethically. In practice such incidents are simply not recognised, covered up altogether or the guilty researcher is urged to retrain, move to another institution or retire from research (5).
  • Ben Goldacre trained as a medical doctor and is the author of the “Bad Science” column in The Guardian. In his book “Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients,” he describes how he ended up prescribing the antidepressant reboxetine to his patients based on insufficient data. Despite the fact that there is overwhelming research which shows that the drug is ineffective, it was still approved in the U.K. In order to get approval of the drug in Europe, the manufacturer had simply kept quiet about its negative data. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had shown a positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. Goldacre had no idea they existed. It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients’ worth of data was left unpublished, and this showed that patients on reboxetine did worse than those on other drugs. He goes on to describe how drug companies hide data about medication risks that affect children, how they attempt to intimidate the employers of researchers who produce results they don’t like, and how they routinely withhold safety data in various other ways that do harm to patients (5).The fundamental problem is that the regulatory bodies, which we would reasonably expect to stamp out such practices have failed us. Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. There is good evidence to demonstrate that the results of research funded by drug companies are highly likely to favour the manufacturer. On the other hand if the results are not favourable then there is absolutely no obligation to make these public. Consequently doctors and patients, only ever see a distorted picture of true effects of any particular drug. In view of the fact that the drug companies are the main source of information to the medical profession this is the picture which becomes widely disseminated. This is reinforced by the fact that the same messages are promulgated through the scientific journals. Although these are usually regarded as objective the reality is that are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by a single drug company (6).

REFERENCES

  1. http://www.wanttoknow.info/pharmaceuticalcorruptionmediaarticles-0-20
  2. http://www.telegraph.co.uk/health/healthnews/10133557/Pharmaceutical-scandal
  3. http://www.thedailybeast.com/newsweek/2011/01/23/why-almost-everything-you-hear-about-medicine-is-wrong.html
  4. http://vernerwheelock.com/?p=545
  5. http://www.theguardian.com/society/2006/may/03/health.medicineandhealth
  6. http://healthland.time.com/2012/09/24/a-doctors-dilemma-when-crucial-new-drug-data-is-hidden/

 

 

 

112. Diabetes can be Cured: Change the Diet and Ditch the Drugs

As a society we seem to have been conditioned to expect that treatment with drugs and other medical procedures are the answer to every form of ill-health. Many of us feel short-changed if we come away from a visit to the GP without a subscription for one or more medicines. However the hard reality is that the NHS expenditure on drugs continues to increase. During 2013-2014 there were 45.1 million items prescribed for diabetes, with a net ingredient cost of £803.1million (1). This represents an increase of 66.5% in the number of items and 56.3% in the net ingredient cost since 2005-2006. In England it is estimated that 6% of the population has diabetes and the total cost is currently about £10billion, which is 10% of the NHS budget (2). It is estimated that by 2025 there will be 5 million people with diabetes in England (3). Those with diabetes have a reduced life expectancy and an increased risk of retinopathy, stroke, kidney failure, heart disease and amputation of limbs.

A man diagnosed with diabetes at age 40 will lose almost 12 years of life and 19 Quality Adjusted Life Years (QALYs) compared with a person without diabetes. A woman of the same age will lose about 14 years of life and 22 QALYs (4).

Unfortunately at present there is little success in controlling the disease. In the light of the current projections, it would seem that there is little confidence that there will be any improvement in the immediate future. Screening for diabetes does not seem to be effective. In a large study conducted in the East of England it was found that screening of patients with increased risk of diabetes was not associated with any reduction in all-cause, cardiovascular, or diabetes-related mortality over a 10-year period (5). There are also serious questions about the effectiveness of treatments of diabetes to lower the blood glucose. In a meta-analysis of data from 13 randomized controlled trials there was no benefit from intensive glucose lowering in terms of all-cause mortality or deaths from cardiovascular disease. in adults with diabetes (6). Furthermore, an increase in all-cause mortality of 19% cannot be ruled out. Only one study showed a protective effect on myocardial infarction but this was counterbalanced by an increase in total mortality. The authors pointed out that drugs for the treatment of diabetes are being approved on the basis of their effectiveness in lowering blood glucose, despite the fact that there is no evidence based on clinically relevant criteria.

The fundamental problem is that the key to overcoming any disease is to identify the root cause and take appropriate steps to eliminate it. In practice, this is rarely done and most of us blithely accept that even though we continue doing whatever caused the disease, it can be overcome by treatment with drugs. The reality is that the best that be achieved with drugs is some alleviation of the symptoms. Even if a “cure” is achieved, the likelihood is that the disease will recur unless the cause is removed. This is very aptly illustrated by the experience of David Servan-Schreiber, who was clinical professor of psychiatry at the University of Pittsburgh School of Medicine (7,8). At the age of 31 he was diagnosed with a brain cancer. A tumour was successfully removed by surgery. He persistently asked the cancer specialists what advice they could give him to prevent the development of another tumour. Much to his surprise they had absolutely no suggestions to offer and even worse they seemed to have no interest. This encouraged him to do his own investigations and in his book (7) he describes what he found out. Much of this related to his lifestyle. As a consequence he made a series of changes, including a complete transformation to his diet. With brain cancer the life expectancy is 2-3 years but Servan-Schreiber managed to survive for another 20 years. Had he just accepted the advice of the medical profession, it is highly unlikely he would have lived for so long.

I cannot over-emphasise the crucial importance of this episode. There must be literally millions of people here in the UK who would benefit from advice on how to avoid diseases and how cures could be achieved by making changes to lifestyle.

Type 2 diabetes (T2D) is responsible for the increased incidence referred to above. There is ample evidence that it can be controlled, possibly even cured completely by making changes to the diet. The condition is directly due to the increased level of glucose in the blood. As a result the pancreas has to produce insulin to keep prevent excess glucose in the body. Excess insulin damages many of the organs, which can eventually lead to a range of diseases. If there is excessive glucose over a prolonged period the pancreas is unable to cope and the glucose becomes rampant, causing all sorts of damage. The solution is obvious. Reduce the amount of glucose which enters the body by altering the diet. Sugar is one of the main culprits, so it should be avoided like the plague. In addition starch is broken down to produce glucose. This means that foods such as refined flour, rice or pasta should be limited because the starch is released quickly giving rise to big increases in the blood glucose.

Essentially this means a diet which is low in carbohydrates (LC). The big problem is that the official advice is to increase carbohydrates. There is a strong possibility that those diagnosed with T2D will be advised to replace fat with carbohydrates. This is fundamentally wrong! The recommendation to reduce fat and especially saturated fat (SFA) does not stand up to rigorous examination. In fact, many of the individual SFAs are important nutrients (9). So what we should be doing is limiting the carbohydrates and consuming plenty of fats. Obviously avoid the trans fats which may be present in manufactured products and are being eliminated by the industry anyway. Despite the marketing claims that polyunsaturates (PUFAs) are good for you because they ”lower cholesterol” I certainly do not recommend them (see 9).

There is now a very convincing case that diets which are low in carbohydrates and high in fat (LCHF) can overcome many of the common chronic diseases. With respect to T2D, there is growing body of scientific research showing that this type of diet is extremely effective in lowering blood glucose and effectively curing T2D provided the LC intake is maintained (10). There are also numerous case studies of individuals who have successfully overcome T2D by making these changes to their diets 11,12).

CONCLUSION

First of all it is essential that all those diagnosed with T2D should be advised to make changes to their diets so that they are LCHF. It is an absolute disgrace that at present they will probably advised to eat more carbohydrates. In any event, the use of drugs should only be used as a last resort or better still not used at all, as there is a lack of evidence that they will be effective.

Even more important is that the official dietary guidelines must be revamped. It is a matter of great concern that we are still being advised to reduce the fat/SFA.

It just does not make sense to carry on as we are at present. The incidence of the disease is getting worse and the costs are increasing. It is becoming unsustainable. We have the answers, all that is needed is that we apply our existing knowledge and the benefits would be enormous.

REFERENCES

  1. http://www.hscic.gov.uk/catalogue/PUB14681/pres-diab-eng-200506-201314-rep.pdf
  2. http://www.diabetes.org.uk/Documents/About%20Us/Statistics/Diabetes-key-stats-guidelines-April2014.pdf
  3. http://www.diabetes.org.uk/Documents/Reports/State-of-the-Nation-2012.pdf      
  4. http://jama.jamanetwork.com/article.aspx?articleid=197439
  5. Rebecca K Simmons et al (2012) http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61422-6/fulltext
  6. Remy Boussageon et al (2011) http://www.bmj.com/content/343/bmj.d4169.pdf%2Bhtml
  7. D Servan-Schreiber(2011) “Anticancer: a new way of life” Penguin Health ISBN 978-0-718-15684-8
  8.  http://vernerwheelock.com/?p=279
  9. http://vernerwheelock.com/?p=153
  10.    http://vernerwheelock.com/?p=226
  11.  http://vernerwheelock.com/?p=229
  12.   http://vernerwheelock.com/?p=405

 

 

 

111. The Institute of Economic Affairs (IEA) Report on Obesity

The IEA has just published a report which concludes that:

“The rise in obesity has been primarily caused by a decline in physical activity at home and in the workplace, not an increase in sugar, fat or calorie consumption” (1).

The report relies mainly on official statistics but is also heavily dependent on the conventional view that obesity is the result of consuming more calories than are expended. Despite the fact that this concept is the basis of official policies in the UK and in many other countries and organisations there are compelling reasons why it is fundamentally flawed. In this blog I will explain why it is not calories per se but sugar/refined carbohydrates, which is the fundamental cause of obesity. In addition I will assess the quality of the information presented on how the consumption of sugar has changed over the past 30-40 years.

The author Christopher Snowdon concludes that the evidence shows that in Britain the per capita consumption of sugar, salt, fat and calories has been falling for decades. In particular, sugar consumption has fallen by 16 per cent since 1992 while calorie consumption has fallen by 21 per cent since 1974.

QUALITY OF THE DATA

The main sources of information are the National Food Survey (NFS) up to 2000, when it was replaced by the Family Food survey. Because these 2 surveys each have different basis, it is not possible to obtain a continuous tracking of the changes. It was not until 1993 that obesity statistics were commenced. Although there has been a steady increase in the incidence of obesity in adults since then the pattern in children is rather different. The information was first collected in 1995 and then there was a peak about 2004 and the decline in recent years has reduced the incidence in 2012 to almost the same level as in 1993.

Although the NFS has limitations it is probably fair to conclude that it does provide a reasonably reliable indicator of trends. This certainly applies to total calories which declined from 2210 in 1980 to 1750 in 2000. The NFS also showed declines in total fat from 106g in1980 to74 in 2000. The corresponding values for total carbohydrate, which of course includes sugar were 264 and 218. The author of the IEA report presents a graph which shows that “sugar” has declined between 1992 and 2012. Presumably the data for the period up to 2000 is from the NFS. I have gone back to the original, which makes it clear that the calculations for the intake of nutrients does not include information on soft drinks and alcoholic drinks and confectionery. All of these contain sugar and if an accurate assessment of the trend is to be determined it is essential that allowance is made for the contribution from these sources. I have also been in touch with the team which is responsible for the food statistics, which has confirmed that there is no reliable information available on the intake of sugars prior to 2000

The difficulties of estimating the intake of sugar are exacerbated by the fact that it is present as an ingredient of many different processed foods, because it is inexpensive and makes foods attractive to the palate. Many of the “low fat” variations of foods are actually formulated by removing the fat and replacing it with sugar. Yoghurts are a typical example. In order to calculate the total intake for the population it is necessary to know the volume of sales and the exact nutrient composition of each particular food. It is a huge and difficult task to do this properly. In Australia the bureau of Statistics simply decided to abandon attempts to produce a reliable value because it was too difficult (and expensive!). Although the UK attempts to deal with this problem, the complexity of the food market and the rapid rate of change mean that it is virtually impossible to obtain reliable information

To sum up, in all probability there has been a substantial drop in the consumption of calories and possibly also in fat. However when it comes to sugar, reliable information is hard to obtain but we can be confident that there is absolutely no credible evidence that there has been a decline in the consumption of sugar. In the light of the substantial increase in the amounts of soft drinks sold, coupled with the growth of sugar-containing processed foods, there are strong indications that total sugar consumption has increased steadily in the period up to 2000.

In recent years, some people are actively cutting down on their sugar consumption, which could mean that for a sector of the population sugar consumption could continue to increase even though the amount for the population as a whole remained constant.

Finally we have to place this in the context of what we know about nutrition. Although many still hold to the view that obesity is caused by consuming more calories than are expended, this has been subject to severe criticism. An excellent example is the work of Zoe Harcombe in her book  “The Oesity Epidemic”(2). For example it has been shown that weight loss by calorie reduction simply does not work (3).Invariably this involves a reduction in fat, which can actually result in an increase in the amount of carbohydrates consumed. Furthermore there is convincing evidence that it is sugar and the refined carbohydrates which are the fundamental cause of obesity (4).In particular, there are compelling studies showing that it is the composition of the diet, which is crucial for obesity to occur. Specifically diets which are high in sugar/refined carbohydrates predispose not only to obesity but also to diabetes, heart disease, various cancers and Alzheimer’s Disease. Conversely, there is now a body of knowledge which demonstrates that diets which are low in carbohydrates and high in fat (LCHF) can be beneficial with respect to a range of diseases/conditions(5). These include heart disease, blood pressure, cancers, body weight and overcoming Type 2 Diabetes.

It follows from this that the crucial issue is the intake of sugar and refined carbohydrates. As I have explained above the Information on sugar is not reliable. The case presented by Christopher Snowdon does not stand up to scrutiny. There is no “English Paradox”. In any event, it is not obesity per se that should be a matter of concern with respect to public health. Much more critical is the growing incidence of diabetes, which has doubled in the past 15 years or so (4). There is absolutely no doubt that this is caused by excessive consumption of sugar and refined carbohydrates.

This report has rather uncanny parallels with what has been happening in Australia, where 2 academics from the University of Sydney have claimed that there is an “Australian Paradox “(6). This was based on a conclusion that the consumption of sugar had declined over the same period that obesity had been increasing. This was disputed by an economist Rory Robertson, who showed convincingly that there was no credible data to demonstrate how the consumption of sugar had changed over the relevant period. He concluded that:

All in all, we are left with a clear sense that there is no “Australian Paradox”, just an idiosyncratic and unreasonable assessment – and avoidance – of the available sugar data by those who coined the phrase” (7).

Because of this he forced the university to set up an inquiry into the activities of the academics with respect to manipulation of the data. The results of the inquiry have recently been announced. Although Christopher Snowdon has claimed that the academics were exonerated, the reality is that the findings were somewhat unequivocal.

Although the adjudicator dismissed the allegations about “research misconduct” it was clear that he was not impressed by the quality of the original “Australian Paradox” paper. He concluded that the paper was not tightly written and contained a number of arithmetic errors. He expressed the view that important new findings would usually be published in a high-impact, rigorously peer-reviewed journal. Subsequently the results would be considered in special edition publications of conference journal format. Clearly this had not been done as the original was published in what was regarded as a ‘soft’ journal, where the quality controls are less stringent. As a consequence it was recommended that a new one be prepared which specifically addresses the key factual issues raised in the inquiry. Furthermore this paper should be written in a constructive manner which respects the issues relating to the quality and reliability of data, raised by Rory Robertson (8).

However, from a close reading of the report it is obvious that there really has been no attempt to deal with many of the serious allegations made by Rory and that effectively it is a rather poor attempt at a “whitewash” (9). A further detailed submission has been prepared by Rory and it is to be hoped that ultimately the issue will be addressed properly (10).

CONCLUSION

So it is evident that this report by IEA does not make any useful contribution to our understanding of the causes of obesity and should be ignored. The fact remains that sugar and refined carbohydrates lie at the root of many of the public health problems not only in the UK but right across the globe.

REFERENCES

  1. http://www.iea.org.uk/sites/default/files/in-the-media/files/Briefing_The%20Fat%20Lie.pdf
  2. Zoe Harcombe (2010) “The Obesity Epidemic” Columbus
  3. http://vernerwheelock.com/?p=221
  4. http://vernerwheelock.com/?p=158
  5. http://www.nutritionjrnl.com/article/S0899-9007(14)00332-3/fulltext
  6. http://vernerwheelock.com/?p=510
  7. http://www.australianparadox.com/pdf/DitchingSugar27032012.pdf
  8. http://vernerwheelock.com/?p=513
  9. http://vernerwheelock.com/?p=517
  10. http://www.australianparadox.com/pdf/RR-response-to-inquiry-report.pdf

 

 

 

 

110. The Tragedy of the Advice to Reduce Fat

There is now very convincing evidence that the recommendations to reduce the intake of fat and especially of saturated fat (SFA) have turned out to be one of the most notable failures in the field of public health policy.

As Nina Teicholz (1) and others have shown, the recommendations can be traced back to Ancel Keys, a researcher at Missouri, who was the lead investigator in the Seven Countries Study.This concluded that that there was a direct correlation between the amount of fat/SFA in the diet of different populations, the level of cholesterol in the blood (TC) and the death rate due to heart disease. It is crucial to emphasise that a correlation does not demonstrate “cause and effect”. This is a fundamental error which has been repeated time and time again in the area of human nutrition. Let me explain with a simple example. If there are numerous police cars observed in a location which has high crime, this does not mean that the crime is caused by the police cars. Reducing the number of police cars will certainly not reduce the crime level. Unfortunately there are many conclusions about nutrition which are reached using this kind of irrational logic. However Keys was even worse than this because he manipulated his data. He actually had data from 22 countries but he used information from just 6 countries, which allowed him to demonstrate that the more fat (and SFA) consumed in a country, the higher the death rate attributed to heart disease. He conveniently omitted:

  • Countries where people eat a lot of fat but have little heart disease, such as Holland and Norway
  • Countries where fat consumption is low but the rate of heart disease is high, such as Chile.

If he had included all his data, then any semblance of a correlation disappeared….the points were all over the place.

For a comprehensive critique of the Seven Countries Study, I can recommend “The Obesity Epidemic” by Zoe Harcombe (2).

Clearly Keys was a very influential in the USA in the sixties and seventies. As a result his views prevailed with the politicians and anyone else who mattered. It is important to appreciate that many distinguished scientists who were opposed to Keys were subjected to a campaign of vilification. John Yudkin, the British nutritionist argued that sugar not fat was the critical factor and was portrayed as a figure of ridicule (3). Keys described Yudkin’s arguments in heart disease “tendentious” and his evidence “flimsy indeed”. Once the policy was in place, it became virtually impossible to criticise it. For example the outstanding nutritionist, David Kritchevsky encountered hysterical opposition which he described to Nina Teicholz as follows:

 

“People would spit on us! It’s hard to imagine now, the heat of the passion. It was just like we had desecrated the American flag. They were so angry that we were going against the suggestions of the American Heart Association and the National Institutes of Health.”

So for the past 30 years or so the advice to lower the fat/SFA has been promoted very powerfully by the public health authorities, supported by the food and pharmaceutical industries. As a result there has been a shift in food consumption with some of the fat being replaced by sugar and other carbohydrates. Although the driving force for the new recommendations was in the USA, the impact has been felt across the globe, primarily because the position adopted by the World Health Organisation (WHO) which was determined largely by the Americans. Unfortunately many other countries took the lead in formulating nutrition policies from the WHO. There is now widespread acceptance that the increase in the consumption of carbohydrate-foods, especially sugar, is the main factor contributing to the so-called “obesity crisis” (4).

It is absolutely essential that we learn from this episode and try to avoid making the same mistakes again. Regrettably we seem to be incapable of doing so as I will demonstrate by considering another current issue, namely salt.

SALT

The official recommendations in the UK are that the population average for adults should be 6g salt per day which translates into 7g/day for men and 5g/day for women (5). The justification is that it will help to lower blood pressure (BP). However it important to note that the reductions which can be achieved by lowering the salt intake are relatively small compared with the levels which are recorded for those suffering from hypertension. It is also assumed that any reduction in BP will result in a corresponding reduction in the risk of heart disease. Furthermore the approach taken by the UK advisory committee has been subject to serious criticism by the Institute of Medicine in the USA (6). On the other hand there are some concerns that there may be dangers in reducing the salt intake to levels that many constitute a danger to health. A recent paper (the PURE study) in the New England Journal of Medicine (6) has collected data on sodium and potassium excretion (to assess the amount consumed) for over 100,000 people in 17 different countries. It was found that those consuming between 7.5 and 15 g salt/day had the lowest risk of death and cardiovascular events. Those with less and those with more had higher values. Clearly we have to be careful about the interpretation of these results. But this study certainly flags up potential dangers. In particular, there is a real possibility that people in the UK who attempt to follow the official advice may finish up with an inadequate intake of salt. If the results of the above study apply to the UK it would mean that current intakes are about right.

Despite this there are some individuals who take a very strong line about salt reduction. At a recent conference Norm Campbell and Graham MacGregor are reported to have stated that:

“Any “controversy” over whether dietary salt is a cause of heart disease and stroke is the result of weak research methodology or commercial interference…”

According to Dr Malcolm Kendrick this can be translated to:

“If you do not believe that excess salt consumption is a cause of heart disease and stroke you are a flawed and misdirected scientist (weak research methodology), or you are corrupt (commercial interference). No other explanation is, of course, possible. You are either an idiot, or corrupt, and therefore – by definition – should be ignored. Or perhaps stoned to death for being an unbeliever.” (8).

The fact that Campbell and MacGregor are also beneficiaries of financial support from various commercial concerns is conveniently not mentioned.

When asked to comment on the PURE study referred to above this is the reaction from Campbell and MacGregor:

“When a member of the audience pointed to the PURE analysis showing that most of the world eats much higher levels of sodium than those recommended by most international organizations, MacGregor and Campbell leaped on this as an example of a study that had radically failed to measure salt in an appropriate fashion, even devising a new “formula” to estimate salt intake because even spot urine testing had been inadequate. “Please let [PURE principal investigator Dr] Salim Yusuf [McMaster University, Hamilton, ON] know that he should stop using spot urine analysis,” MacGregor said curtly.”(9).

Malcolm Kendrick sums it up very nicely

“.. the main point here is the fact that we have more bully boy tactics going on. Two ‘grand fromages’ take the stage to beat the opposition into pulp”.

We know that salt (sodium) is an essential nutrient and that a certain amount must be included in the diet. Very large amounts may be damaging to health. We simply do not know accurately the optimum range of intakes. It may well be that for a substantial proportion of the population, there is no need to alter the intake. Under these circumstances, in my view, it is totally irresponsible to advocate a change. Before any official advice is recommended we have to be certain that there will be an improvement in health as a result. Even more important there must be no possibility that of harm to those who follow the advice.

The parallels with Ancel Keys are much too close for comfort. There is a total failure to try to deal with the actual evidence and the name of the game is to use anything to win your case and denigrate those with the temerity to have a contrary view. It is obvious that there is not a cast iron case for reducing salt. There is a distinct possibility that lowering current intakes may well have a damaging effect. Rather ironically those most at risk would be the people who take the advice seriously and try to comply with the recommendations. We really must learn from the mistakes of the past. The lesson is that we have to have a very convincing rationale before advising how the diet should be changed.

REFERENCES

  1. Nina Teicholz. (2014)“The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet” Simon & Shuster New York
  2. Zoe Harcombe (2010) “The Obesity Epidemic” Columbus p 87
  3. Gary Taubes (2007) “The Diet Delusion” Vermillion: London p120
  4. http://vernerwheelock.com/?p=158
  5. http://www.sacn.gov.uk/pdfs/sacn_salt_final.pdf
  6. http://vernerwheelock.com/?p=293
  7. http://www.nejm.org/doi/full/10.1056/NEJMoa1311889
  8. http://drmalcolmkendrick.org/2014/06/22/calling-all-physicians-the-salt-debate-must-stop/
  9. 9.       http://www.medscape.com/viewarticle/826970?src=emailthis

 

 

 

109. Cochrane Collaboration Evaluates Statins for Primary Prevention of Heart Disease

The Cochrane Collaboration has established a unique reputation for the publication of reports on a variety of topics in the medical field. This is an area where there are very powerful vested interests and the quality of much of the research is questionable. Therefore the contribution of the Collaboration has proved to be extremely valuable with respect to decisions on treatment and policy formulation.

In recent years the Collaboration has produced two reports which focus on the use of statins for the primary prevention of heart disease. In the first one it was concluded that caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk (1). However in the second on e published 2 years later, the conclusion was that the totality of evidence now supports the benefits of statins for primary prevention(2). In this blog I will attempt to discover why and how there has been such a radical shift in position.

At the outset I should emphasise, that I consider the critical information to assess the value of these drugs is all-cause mortality. First of all, there can be no argument about the validity of the “diagnosis”. Secondly, this is what most patients will wish to know. It not much comfort if a reduction in the risks of death from heart disease is counterbalanced by an increased risk of dying from another disease. It is also important to have reliable information on adverse side-effects. Many patients are likely to question the value of an extra few months on this earth if the quality of life is made miserable by the drugs.

The first report which was released in January 2013 included research up to September 2007. This was based on 14 trials (with 16 trial arms) involving 34,272 participants. The mean age of the participants was 57 years (age range 28-50), 65.0% were male. However data on all-cause mortality was only provided in 8 trials. Furthermore in 2 trials which accounted for over one quarter of the participants were stopped prematurely.

The report noted that all but one of the trials had some form of pharmaceutical industry sponsorship. Research has shown that the results of trials sponsored by the pharmaceutical industry- are more likely than non-industry-sponsored trials to report results and conclusions that favour drug over placebo because of biased reporting and/or interpretation of trial results (3). As a consequence:

“In primary prevention where world-wide the numbers of patients eligible for treatment are massive, there might be motivations to use composite outcomes and early stopping to get results that clearly support intervention.”

The authors concluded that the review:

highlights the shortcomings in the published trials of statins for primary prevention. Selective reporting and inclusion of people with cardiovascular disease in many of the trials included in previous reviews of their role in primary prevention make the evidence impossible to disentangle without individual patient data. In people at high risk of cardiovascular events due to their risk factor profile (i.e. 20+% 10-year risk), it is likely that the benefits of statins are greater than potential short term harms although long-term effects (over decades) remain unknown. Caution should be taken in prescribing statins for primary prevention among people at low cardiovascular risk.”

As soon as the report was published, there was an objection from Rory Collins and Colin Baigent of the Cholesterol Treatment Trialists’ (CTT) Collaboration at the University of Oxford. Their concern was the report had stated that the CTT collaborators had not published information about the proportional and absolute benefits of statin therapy among people with no prior history of vascular disease. They referred specifically to a paper published in The Lancet in 2010.They also objected to a statement in the press release announcing the release of the report which was as follows:

Given that low cholesterol has been shown to increase the risk of death from other causes, statins may do more harm than good in some patients”.

In reply the lead author Shah Ebrahim pointed out that the CTT Lancet paper of 2010 was not available at the time the review was completed. However he insisted that the estimate of the effects of lowering LDL cholesterol with respect to major vascular events, contained in the review, was similar to that of the CTT. He also re-iterated his surprise that the CTT did not provide more information on other outcomes among participants taking statins for primary prevention. He drew attention that others have raised the issue of all-cause mortality in primary prevention trials (4) and that there are particular concerns about increased risk of diabetes in people who take statins (5).

With respect to the press release, the point was accepted and a correction was issued.

Now we come to the second report which was published in January 2013 (2). This included research which was published up to the beginning of January 2012 and was based on 18 trials (with 19 trail arms) with 56,934 participants. The mean age was 57 years and 60.3% were men.

Thirteen trials with 48,060 participants recruited reported on total mortality. In the statin group 1077 out of 24,408 people died (4.4%) whereas in the control group there were 1223 deaths out of 23,652 (5.1%). This translates into an Numbers Needed to Treat (NNT) of 96 which means that 96 people have to be treated for 5 years for one to benefit. Furthermore it is crucial to appreciate that this means 96 people have to be treated for 5 years for one to benefit.

There was a reduction in various end-points related to cardiovascular disease (CVD) which were associated with falls in total cholesterol (TC) and LDL cholesterol in trials which reported these outcomes. The review concluded that adverse side-effects were not excessive although not all trials reported these fully. . Patients’ perception of quality of life was reported in only one trial and this showed limited benefit.

It is also interesting to note that in this report it was stated that:

“there was low risk of bias ….though all trials were either fully or partially funded by pharmaceutical companies”

What is especially noteworthy is that this review makes detailed reference to the work of the CTT.

In particular:

  • The CTT Collaboration has published analyses focusing on the comparison between high and low doses of statins which demonstrate that more intensive treatment lowers LDL cholesterol more, resulting in greater benefits with no excess risk of non-vascular mortality (6).
  • Strong evidence of the absence of any adverse effects on cancer risk is also confirmed by a further CTT Collaboration report (7).
  • The Cochrane estimates of the effects on all-cause mortality are in agreement with those of the CTT (8). Although it does accept that there is an increased risk of myopathy and rhabdomyolysis in those treated with statins especially in those treated with high (9). These benefits equate to an NNT of 167 for people with a <5% five year risk for heart disease and 67 for those with a 5-10% risk. This means that for those with the lower risk 167 people have to be treated for 5 years for one to benefit and 67 for those with the higher risk

The final conclusion is that benefits of statins outweigh any serious adverse effects. Hence earlier claims that statins provide no overall benefit in primary prevention in terms of all-cause mortality can no longer be substantiated.

This represents an about turn in the space of 2 years. Here are a few comments which I believe are worth addressing if you are mystified by this complete reversal in the position reached by the Cochrane authors.

It is evident that the research from the CTT has been highly influential with the authors when coming to their final conclusion. I just wonder if they were aware of the criticisms of the work of the CTT by Dr David Newman (10). He points out that the CTT does not compare those who were on statins with the corresponding controls. Instead they selected those individuals in which the statin treatment reduced the LDL Cholesterol 1 mmol/L or 40 points in US terms. As Dr Newman describes it:

“…they shifted the data so that their numbers corresponded precisely to patients whose cholesterol responded perfectly.”

He continues:

 “Patients whose cholesterol drops 40 points are different than others, and not just because their body had an ideal response to the drug. They may also be taking the drug more regularly, and more motivated. Or they may be exercising more, or eating right, and more health conscious than other patients. So it should be no surprise that this analysis comes up with different numbers than a simple comparison of statins versus placebo pills. Ultimately, then, this new information tells us little or nothing about the benefits someone might expect if they take a statin. Instead it tells us the average benefits among those who had a 40-point drop in LDL.”

Furthermore the LDL Cholesterol drop cannot be predicted because the effect of the statins is unknown. This means that the conclusions of this analysis have absolutely no relevance to patients and doctors who have to decide if statins should be prescribed.

Here is a final quote from Dr Newman:

“Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However the authors’ conclusions imply that they answered a different, much bigger question. And that is not a true story.”

It seems to me that this is a very valid criticism because the CTT studies do not include those who were on statins but failed to lower their LDL Cholesterol. I am not aware that anyone has answered Dr Newman’s critique. Incidentally this would explain why the CTT does not agree with other analyses which find that the use of statins as a preventive measure does not reduce all-cause mortality.

The CTT data on side- effects are entirely dependent on the results which were obtained from trials. Serious doubts have been raised. Rather ironically the second Cochrane report accepted that the reporting of adverse events in these trials is generally poor, with failure to provide details of severity and type of adverse events or to report on health-related quality of life. It then went on to conclude rather complacently:

“However, it seems unlikely that any major life-threatening hazards associated with statin use exist”.

Recently Sir Richard Thompson , President of the Royal College of Physicians and colleagues wrote to NICE expressing concern about the proposal to extend the use of statins to those with a low risk of developing CVD (11). The letter commented specifically on side-effects as follows:

“I am in no doubt, both personally and from the reported experience of my patients, that statin side-effects are consistently under-reported. This occurs two ways; firstly, doctors airily dismiss symptoms reported by patients (“statins could not possibly cause that!”), and secondly it is unusual for well-recognised side-effects such as rhabdomyolysis or even non-specific muscle pains to be yellow-carded. In my view the potential severity of muscle symptoms justifies extreme caution”

The argument was supported by information on the number of adverse side-effects in various stain trials, which is shown here in Table 1.

Table 1 Adverse side-effects reported in various statin trial

Trial, Name of statin Side-effects, statin treatment,% Side-effects,control,%
AFCAPS/TEXCAPS Losartan 13.6 13.8
4S simvastatin 6.0 6.0
CARDS atorvastatin 25.0 24.0
METEOR rosuvastatin 83.3 80.4
LIPID Pravastatin 3.2 2.7
JUPITER Rosuvastatin 25.0,discontinuation,

15.0,serious side-effects

25.0, discontinuation,

!5.5, serious side-effects

WOSCOPS Pravastatin 7.8 7.0

Note: The values shown refer to “total adverse effects” unless otherwise indicated

What is quite remarkable about these figures is the similarity between those for the group treated and those for the controls. Furthermore the variation is huge. In one the values are as low as 3% but in another it is over 80%. The reality is that the companies have little interest in collecting data on side-effects. The information shown above clearly demonstrates the information on side-effects obtained in clinical trials simply lack credibility.

The letter also referred to the fact that independent researchers do not have access to raw data and noted that:

“…the data driving NICE guidance on statins comes almost entirely from pharmaceutical company funded studies. Furthermore, these data are not available for review by independent researchers, only those who work for the Oxford Cholesterol Treatment Trialists Collaboration (CTT).

The CTT has commercial agreements with pharmaceutical companies which apparently means that they cannot release data to any other researchers who request to see it. Which, in turn, means that the latest reviews of the data by NICE and also by the Cochrane group are totally reliant on the CTT 20121 meta-analysis analysis of this concealed data?”

It is highly relevant that in the recent BMJ controversy it has emerged that the CTT at Oxford University has had funding from drug companies of about £268million as Zoe Harcombe has revealed (12).

There have to be very strong suspicions that the Cochrane authors have allowed themselves to be bullied into submission by the actions of Rory Collins and Colin Baigent. It is evident from the information I have presented here that they have ignored key considerations, which ought to have had an impact in reaching their conclusions. Perhaps they should have studied another Cochrane publication entitled “Eminence v Evidence” (13) which makes some extremely pertinent comments.

This is a great pity because if ever there was a need for a body which can conduct an authoritative evaluation of the evidence it is now. It is to be hoped that the powers that be in Cochrane will take these points on board. Above all its contributors must stand up to bully boy tactics of the very powerful vested interests. Many will be familiar with the fact that Rory Collins tried the same tactic with the BMJ. To her great credit Fiona Godlee , the editor-in-chief was not intimidated by Collins and effectively took appropriate action which put him in his place. Cochrane could well to learn some lessons from this.

Finally, even if the conclusions of the second Cochrane report are genuine, let us consider this from the perspective of those who will be prescribed statins in accordance with the latest NICE guidelines. These mean that those with a 10% risk of developing CVD will be advised to go on statins. Effectively this means everyone over 50, because no matter how fit and healthy a person is, when the time comes there must be at least a 1 in 10 chance that the cause of death will be heart disease. Cochrane states that 67 people will have to be treated for 5 years for one person to benefit. Although according to Mark Baker of NICE, 77 will have to be treated for 3 years. Whatever the figure the chances are very small. Cochrane comments:

These NNTs are well within the range considered worthwhile in primary prevention

Well I have got news for the authors and for the medical professions as a whole if this is statement is an accurate reflection of its opinion. It is certainly not acceptable to me and I strongly suspect to the vast majority of patients. In my experience most people believe that if they are prescribed a drug it will effective for them personally. They might be prepared to accept that there may be less that 100% certainty, possibly as low as 20%, which is an NNT of 5! It is crucial that we are concerned here with prevention. I recognize that it is rather different for a person with a serious illness, who will clutch at anything that may be effective. But prevention is a new ball game and in my opinion, there would be very few who would agree to statins if they were aware that there was only a 1 in 67 chance that it would do them any good.

For anyone who is concerned that their risk of CVD is high and they wish to lower them, what should they do? Here are some suggestions:

  • If you smoke cigarettes, stop immediately
  • Take regular exercise, If you can walk at least 1 mile per day, this will certainly imlrove your life expectancy
  • Make adjustments to your diet. There is now very convincing evidence that restricting the intake of sugar and refined carbohydrates will reduce the risks not only of CVD but also of diabetes, cancer, Alzheimer’s Disease as well as lowering blood pressure and achieving weight loss

There is absolutely no doubt any benefits derived from statin treatment will be insignificant when compared those which can be achieved by implementing the measures outlined above. Furthermore, any side-effects will be minimal compared to those experienced by people on statins.

So whatever way you look at it, the case for statins just does not stack up. The truth is that the fundamental objective is the profitability of the drug companies and improving public health simply does not feature. In fact, if statins were only used to treat patients suffering from CVD, this could be a critical step towards good health. It would definitely release funds which could be better in spent in other ways, such as employing more nurses.

It is a matter of great regret that this particular Cochrane team did not follow the example of the one led by Tom Jefferson, which considered neuraminida inhibitors including Tamiflu (14). The background has been explained in an article in The Guardian by Ben Goldacre (15). An earlier Cochrane report had concluded that these ‘flu drugs do reduce the rate of complications of conditions such as pneumonia. However a paediatrician in Japan pointed out that the Cochrane report was based on the results of 2 published trials of which only one showed a positive response. In fact there were another 8 trials, for which the results had never seen the light of day and all of these had been negative!! As a direct result of this Tom Jefferson realised that in the 2008 report they had made a mistake in relying on the published data. So he decided to see if he could get hold of the information. There was a long battle with Roche, which by this time controlled the data, before the company eventually sent documents containing excerpts, which did not provide adequate information to assess the benefits and the adverse side-effects. It was also not possible to consider the details of the trial procedures, which is essential if the quality of the data is to be evaluated.

Consideration of the work of various regulatory agencies such as the FDA in the USA and EMEA in the EU indicated that there were serious flaws in the procedures. As Cochrane had not been provided with the detailed information it needed to do its review properly, it decide to exclude all this data from the analysis. Effectively it was unable to reach a conclusion and explained the position in a further review published in December 2009. This was followed by a long period of prevarication by Roche, including claims that some of the Cochrane researchers had made untrue statements about the drug and the company and allegations questioning their independence. Finally under pressure from the BMJ which supported the Cochrane investigators, Roche agreed to release all the data but it had taken 5 years for this to happen.

When this information was evaluated, the review was finally published in April 2014. Because the team now had the clinical study reports (CSRs) from the manufacturers it was able to compare the information with that which had been submitted to the regulatory authorities. Rather significantly it was decided not to use results which appeared in scientific journals because in previous versions of this review unresolved discrepancies in the data presented were identified in published trial reports. Substantial publication bias was also uncovered.

Based on these assessments of the regulatory documents (in excess of 160,000 pages), it was concluded that there were substantial problems with the design, conduct, reporting and availability of information from many of the trials. As a consequence, there were doubts about the reliability of the results. The review was based on 20 trials with zanamir (Relenza, from GSK) and 26 trials with oseltamir (Tamiflu fom Roche). It was found that:

both drugs shorten the duration of symptoms of influenza-like illness (unconfirmed influenza or ‘the flu’) by less than a day. Oseltamivir did not affect the number of hospitalisations, based on the data from all the people enrolled in treatment trials of oseltamivir. Zanamivir trials did not record this outcome. The effects on pneumonia and other complications of influenza, such as bronchitis, middle ear infection (otitis media) and sinusitis, were unreliably reported, as shown by the case report form in the trial documents. Some forms showed limitations in the diagnostic criteria for pneumonia. Regulatory comments noted problems with missing follow-up diary cards from participants. In children with asthma there was no clear effect on the time to first alleviation of symptoms.

Prophylaxis trials showed that oseltamivir and zanamivir reduced the risk of symptomatic influenza in individuals and households. There was no evidence of an effect on asymptomatic influenza or on non-influenza, influenza-like illness, but trial conduct problems prevent any definitive conclusion.

Oseltamivir use was associated with nausea, vomiting, headaches, renal and psychiatric events; these last three were when it was used to prevent influenza (prophylaxis). Its effect on the heart is unclear: it may reduce cardiac symptoms, but may induce serious heart rhythm problems. In adult treatment trials of zanamivir there was no increased risk of reported adverse events. The evidence on the possible harms associated with the treatment of children with zanamivir was sparse.”

This is not exactly impressive. Roche put out a press release contesting these findings but did not provide any reasons. When the benefits are balanced against the side-effects, it is difficult to justify their use. It was certainly a huge waste of money by the government to spend £500 million to stockpile supplies of this drug. But that is what happens when all the relevant data to make an informed decision is not available.

When this episode is compared with the performance of the team dealing with statins, a sad state of affairs emerges. In contrast to Tom Jefferson, the statin team seems to have just submitted to the power and influence of the industry and its supporters. There has been a total failure to insist on getting access to the primary data. As the Tamiflu review clearly demonstrates  when the original reports become available for assessment, the perspective is completely different. In the light of this, there have to be very strong suspicions that if and when the relevant statin data is released generally, we will find that the benefit/adverse side-effects ratio is very much worse than we have been led to believe.

Commenting on the Tamiflu review, Dr David Tovey, Editor-in-Chief of The Cochrane Library said:

“We now have the most robust, comprehensive review on neuraminidase inhibitors that exists. Initially thought to reduce hospitalisations and serious complications from influenza, the review highlights that [NIs are] not proven to do this, and it also seems to lead to harmful effects that were not fully reported in the original publications. This shows the importance of ensuring that trial data are transparent and accessible” (17).

Let’s hope that one day he will be able to say the same about statins.

REFERENCES

  1.  http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004816.pub4/full
  2. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004816.pub5/full
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  11. http://drmalcolmkendrick.org/2014/06/27/another-backlash-begins/
  12. http://www.zoeharcombe.com/2014/08/ctsu-funding-from-drug-companies/
  13. http://www.cochrane.org/news/blog/eminence-vs-evidence
  14. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD008965.pub4/full
  15. http://www.theguardian.com/business/2014/apr/10/tamiflu-saga-drug-trials-big-pharma
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  17. http://www.cochrane.org/features/tamiflu-and-relenza-getting-full-evidence-picture