LOB-vs
Download Lectures on Biostatistics (1971).
Corrected and searchable version of Google books edition

Download review of Lectures on Biostatistics (THES, 1973).

Latest Tweets
Categories
Archives

diet

Sarah Ferguson, ex-wife of Prince Andrew, Duke of York, seems to need a lot of money. Some of her wheezes are listed in today’s Times. That’s behind a paywall, as is the version reproduced in The Australian (Murdoch connection presumably). You can read it (free) here, with more details below the article.

Duchess

Thomas Ough and David Brown

Published at 12:01AM, January 15 2015

In her seemingly endless quest to make money, Sarah, Duchess of York, has had little hesitation using her title to generate sales.

This week, though, she landed herself in trouble after appearing to use the name of Britain’s foremost scientific university to lend credibility to a promotion for her new diet system.

The duchess told NBC’s Today show during an interview to promote her “emulsifier” programme that she was aware of the dangers of obesity through her work as an ambassador for the Institute of Global Health Improvement at Imperial College London.

Last night she apologised for “any misunderstanding” after Imperial College, ranked the joint second-best university in the world, sought to distance itself from the duchess’s promotion.

A spokesman said: “The commercial activities promoted by Sarah Ferguson in the interview with Today are not connected in any way to Imperial’s staff or research activities, and the college does not endorse the suggestion of any possible link.”

The institute, which has more than 160 specialists, including clinicians, engineers, scientists and psychologists, is headed by Lord Darzi of Denham, a former Labour health minister.

The duchess told the Today presenter Matt Lauer that she had been a comfort eater since the age of 12 but the “turning point” was when she realised that she was the same weight as when pregnant with Princess Beatrice, now 25.

“I couldn’t bear looking at myself any minute longer,” she confided. “In fact, the size of my ass probably saved my life.” She said she discovered that the “emulsifier” was “a solution for behavioural change” and helped her to lose 55lbs. The $99 kit, which includes a blender, a couple of recipe books and some workout DVDs, is produced by Tristar Products, a direct marketing company for home and health items.

The duchess told the breakfast show: “I have just found out on my discoveries with Imperial College London . . . I’m an ambassador for the Institute for Global Health Innovation, and I found out that children, little children, are going to die before their parents because of obesity.”

The benefits of the kit were questioned yesterday by Ayela Spiro, a senior scientist at the British Nutrition Foundation.

She said: “In terms of the particular product, no juicer or blender on their own can enhance how much nutrition your body will absorb. Any claims made about such products such that it accelerates weight loss, boosts energy and strengthens the immune system need to be treated with caution.”

Professor David Colquhoun of University College London, said: “I find it pretty amazing that Imperial chose someone like her to be an ‘ambassador’. Imperial does have an interest in appetite suppression but hasn’t come up with any usable product yet and this research has nothing to do with blenders.

“[Her television appearance] was sheer name-dropping, something she’s quite good at. The only ‘discovery’ she seems to have made is that if you eat less you’ll lose weight. The $100 blender has nothing to do with it.”

A spokesman for the duchess said: “She is not trying to use her association with the institute to promote her personal interests. She was talking about ‘behavioural change’, which is endorsed by the institute, and her own behavioural change.”

With the article there’s an inset that gives details of other ways in which Sarah Ferguson has exploited her title to make money.

duchess business

Fergie’s latest wheeze, Duchess Discoveries is being promoted heavily on US television. It bears a close resemblance to those ghastly daytime TV advertising channels. Watch her interview on a US TV programme, "Today".

It’s partly promoting her latest diet scam, and partly a vigorous defence of her ex-husbands innocence in the face of allegations of sexual shenanigans. Of course she doesn’t know whether the allegations are true. The Queen doesn’t know (so why bother with the denial from Buckingham Palace?). And I don’t know. We know plenty about Prince Andrew’s bad behaviour, but we don’t know whether he’s had sex with minors.

Worse still is the promotional video on the “Duchess Discoveries” site itself.

I quote:

“I’m SO excited about my fusion accelerator system, accelerates weight loss, accelerates your energy, accelerates and strengthens your immune system.”

"accelerates weight loss" is certainly unproven. Mere hype

"accelerates your energy" is totally meaningless. It’s the sort of sciencey-sounding words that are loved by all quacks.

"accelerates and strengthens your immune system". Sigh. "strengthening the immune system is the perpetual mantra of just about every quack. It’s totally meaningless. Just made-up nutribollocks.

The promotional video is fraudulent nonsense. If it were based in the UK I have no doubt that it would be quickly slapped down by the Advertising Standards Authority. But in the USA the first amendment allows people to lie freely about nutrition, which is why it’s such big business.

It bothers me that the most that the best that the British Nutrition Foundation could manage was to say that such claims "need to be treated with caution". They are mendacious nonsense. Why not just say so?

Follow-up

Jump to follow-up

This article has been re-posted on The Winnower, so it now has a digital object identifier: DOI: 10.15200/winn.142935.50603

The latest news: eating red meat doesn’t do any harm. But why isn’t that said clearly? Alarmism makes better news, not only for journalists but for authors and university PR people too.

I’ve already written twice about red meat.

In May 2009 Diet and health. What can you believe: or does bacon kill you? based on the WCRF report (2007).

In March 2012 How big is the risk from eating red meat now? An update.

In the first of these I argued that the evidence produced by the World Cancer Research Fund (WCRF) for a causal relationship was very thin indeed. An update by WCRF in 2010 showed a slightly smaller risk, and weakened yet further the evidence for causality, though that wasn’t reflected in their press announcement.

The 2012 update added observations from two very large cohort studies. The result was that the estimates of risk were less than half as big as in 2009. The relative risk of dying from colorectal cancer was 1.21 (95% Confidence interval 1.04–1.42) with 50 g of red or processed meat per day, whereas in the new study the relative risk for cancer was only 1.10 (1.06-1.14) for a larger ‘dose’, 85 g of red meat. Again this good news was ignored and dire warnings were issued.

This reduction in size of the effect as samples get bigger is exactly what’s expected for spurious correlations, as described by Ioannidis and others. And it seems to have come true. The estimate of the harm done by red meat has vanished entirely in the latest study.

The EPIC study

This is the European Prospective Investigation into Cancer and Nutrition, another prospective cohort study, so it isn’t randomised [read the original paper]. And it was big, 448,568 people from ten different European countries. These people were followed for a median time of 12.7 years, and during follow-up 26,344 of them died.

The thing that was different about this paper was that red meat was found to pose no detectable risk, as judged by all-cause mortality. But this wasn’t even mentioned in the headline conclusions.

Conclusions: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.

To find the result you have to dig into Table 3.

Table 3

So, by both methods of calculation, the relative risk from eating red meat is negligible (except possibly in the top group, eating more than 160 g (7 oz) per day).

There is still an association between intake of processed meat and all-cause mortality, as in previous studies, though the association of processed meat with all-cause mortality, 1.09, or 1.18 depending on assumptions, is, if anything, smaller than was observed in the 2012 study, in which the relative risk was 1.20 (Table 2).

Assumptions, confounders and corrections.

The lowest meat eaters had only 13% of current smokers, but for the biggest red meat eaters it was 40%, for males. The alcohol consumption was 8.2 g/day for the lowest meat eaters but 23.4 g/day for the highest-meat group (the correlations were a bit smaller for women and also for processed meat eaters).

These two observations necessitate huge corrections to remove the (much bigger) effects of smoking and drinking if we want find the association for meat-eating alone. The main method for doing the correction is to fit the Cox proportional hazards model. This model assumes that there are straight-line relationships between the logarithm of the risk and the amount of each of the risk factors, e.g smoking, drinking, meat-eating and other risk factors. It may also include interactions that are designed to detect whether, for example, the effect of smoking on risk is or isn’t the same for people who drink different amounts.

Usually the straight-line assumption isn’t tested, and the results will depend on which risk factors (and which interactions between them) are included in the calculations. Different assumptions will give different answers. It simply isn’t known how accurate the corrections are when trying to eliminate the big effect of smoking in order to isolate the small effect of meat-eating. And that is before we get to other sorts of correction. For example, the relative risk from processed meat in Table 3, above, was 9% or 18% (1.09, or 1.18) depending on the outcome of a calculation that was intended to increase the accuracy of food intake records ("calibration").

The Conclusions of the new study don’t even mention the new result with red meat. All they mention is the risk from processed meat.

In this population, reduction of processed meat consumption to less than 20 g/day would prevent more than 3% of all deaths. As processed meat consumption is a modifiable risk factor, health promotion activities should include specific advice on lowering processed meat consumption. 

Well, you would save that number of lives if, and only if, the processed meat was the cause of death. Too many epidemiologists, the authors pay lip service to the problem of causality in the introduction, but then go on to assume it in the conclusions. In fact the problem of causality isn’t even metnioned anywhere in either the 2012 study, or the new 2013 EPIC trial.

So is the risk of processed meat still real? Of course I can’t answer that. All that can be said is that it’s quite small, and as sample sizes get bigger, estimates of the risk are getting smaller. It wouldn’t be surprising if the risk from processed meat were eventually found not to exist, just as has happened for red (unprocessed) meat

The Japanese study

Last year there was another cohort study, with 51,683 Japanese. The results were even more (non-) dramatic [Nagao et al, 2012] than in the EPIC trial. This is how they summarise the results for the relative risks (with 95% confidence intervals).

"…for the highest versus lowest quintiles of meat consumption (77.6 versus 10.4 g/day) among men were 0.66 (0.45 — 0.97) for ischemic heart disease, 1.10 (0.84 — 1.43) for stroke and 1.00 (0.84 — 1.20) for total cardiovascular disease. The corresponding HRs (59.9 versus 7.5 g/day) among women were 1.22 (0.81 — 1.83), 0.91 (0.70 — 1.19) and 1.07 (0.90 — 1.28). The associations were similar when the consumptions of red meat, poultry, processed meat and liver were examined separately.

CONCLUSION: Moderate meat consumption, up to about 100 g/day, was not associated with increased mortality from ischemic heart disease, stroke or total cardiovascular disease among either gender."

In this study, the more meat (red or processed) you eat, the lower your risk of ischaemic heart disease (with the possible exception of overweight women). The risk of dying from any cardiovascular disease was unrelated to the amount of meat eaten (relative risk 1.0) whether processed meat or not.

Of course it’s possible that things which risky for Japanese people differ from those that are risky for Europeans. It’s also possible that even processed meat isn’t bad for you.

The carnitine study

The latest meat study to hit the headlines didn’t actually look at the effects of meat at all, though you wouldn’t guess that from the pictures of sausages in the headlines (not just in newspapers, but also in NHS Choices). The paper [reprint] was about carnitine, a substance that occurs particularly in beef, with lower amounts in pork and bacon, and in many other foods. The paper showed that bacteria in the gut can convert carnitine to a potentially toxic substance, trimethylamine oxide (TMAO). That harms blood vessels (at least in mice). But to show an effect in human subjects they were given an amount of carnitine equivalent to over 1 lb of steak, hardly normal, even in the USA.

The summary of the paper says it is an attempt to explain "the well-established link between high levels of red meat consumption and CVD [cardiovascular disease] risk". As we have just seen, it seems likely that this risk is far from being “well-established”. There is little or no such risk to explain.

It would be useful to have a diagnostic marker for heart disease, but this paper doesn’t show that carnitine or TMAO) is useful for that. It might also be noted that the authors have a maze of financial interests.

Competing financial interests Z.W. and B.S.L. are named as co-inventors on pending patents held by the Cleveland Clinic relating to cardiovascular diagnostics and have the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics from Liposciences. W.H.W.T. received research grant support from Abbott Laboratories and served as a consultant for Medtronic and St. Jude Medical. S.L.H. and J.D.S. are named as co-inventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics patents. S.L.H. has been paid as a consultant or speaker by the following companies: Cleveland Heart Lab., Esperion, Liposciences, Merck & Co. and Pfizer. He has received research funds from Abbott, Cleveland Heart Lab., Esperion and Liposciences and has the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics from Abbott Laboratories, Cleveland Heart Lab., Frantz Biomarkers, Liposciences and Siemens.

The practical significance of this work was summed up the dietitian par excellence, Catherine Collins, on the BBC’s Inside Health programme.

Listen to Catherine Collins on carnitine.

She points out that the paper didn’t mean that we should change what we already think is a sensible diet.

At most, it suggests that it’s not a good idea to eat 1 lb steaks very day.

And the paper does suggest that it’s not sensible to take the carnitine supplements that are pushed by every gym. According to NIH

"twenty years of research finds no consistent evidence that carnitine supplements can improve exercise or physical performance in healthy subjects".

Carnitine supplements are a scam. And they could be dangerous.

Follow-up

Another blog on this topic, one from Cancer Research UK also fails to discuss the problem of causality. Neither does it go into the nature (and fallibility) of the corrections for counfounders like smoking and alcohol,. Nevertheless that, and an earlier post on Food and cancer: why media reports are often misleading, are a good deal more realistic than most newspaper reports.

There is no topic more widely discussed than what one should eat in order to stay healthy. And there are few topics where there evidence is so lacking in quality. This post isn’t about quackery, but about something much more important. it is about the real science (if it merits that description) behind dietary advice.  I’m not an expert in nutrition, but I do know a bit about the nature of evidence. I’m continually astonished by the weakness of the evidence for some things that have become received truths, and nowhere is that more true than in nutrition.

The BMJ used my review of Gary Taube’s book, The Diet Delusion, to start off their new Round Table feature [full text link to BMJ].

The published version had some big cuts so I publish the original version here.  Taubes was kind enough to send me a copy of the book after I’d mentioned his wonderful New York Times piece in my previous excursion into the murky world of diet and health, Diet and health. What can you believe: or does bacon kill you?

diet delusion cover

The biggest omission in the BMJ version was Taubes’ own ten point summary of his conclusions (on page 454).

"“As I emerge from this research, though, certain conclusions seem inescapable to me, based on existing knowledge

  1. Dietary fat, whether saturated or not, is not a cause of obesity, heart disease, or any other chronic disease of civilization
  2. The problem is the carbohydrates in the diet, their effect on insulin secretion, and thus the hormonal regulation of homeostasis – the entire harmonic ensemble of the human body.  The more easily digestible and refined the carbohydrates, the greater the effect on our health, weight, and well-being.
  3. Sugars – sucrose and high-fructose corn syrup specifically – are particularly harmful, probably because the combination of fructose and glucose simultaneously elevates insulin levels while overloading the liver with carbohydrates.
  4. Through their direct effect on insulin and blood sugar, refined carbohydrates, starches, and sugars are the dietary cause of coronary heart disease and diabetes.  They are the most likely dietary causes of cancer, Alzheimer’s disease, and the other chronic diseases of civilization.
  5. Obesity is a disorder of excess fat accumulation, not overeating, and not sedentary behaviour.
  6. Consuming excess calories does not cause us to grow fatter, any more than it causes a child to grow taller.  Expending more energy than we consume does not lead to long-term weight loss; it leads to hunger.
  7. Fattening and obesity are caused by an imbalance – a disequilibrium – in the hormonal regulation of adipose tissue and fat metabolism.  Fat synthesis and storage exceed the mobilization of fat from the adipose tissue and its subsequent oxidation.  We become leaner when the hormonal regulation of the fat tissue reverses this balance.
  8. Insulin is the primary regulator of fat storage.  When insulin levels are elevated – either chronically or after a meal – we accumulate fat in our fat tissue.  When insulin levels fall, we release fat from our fat tissue and use it for fuel. 
  9. By stimulating insulin secretion, carbohydrates make us fat and ultimately cause obesity.  The fewer carbohydrates we consume, the leaner we will be.
  10. By driving fat accumulation, carbohydrates also increase hunger and decrease the amount of energy we expend in metabolism and physical activity.”

It is on these bases that Taubes suggests that the increase in obesity is, in part, a consequence of the recommendation of a  low fat, and hence high sugar diet.

The Diet Delusion [ pp 601]

(published in the USA as Good Calories, Bad Calories)

Gary Taubes 2008

There is no topic more widely discussed than what one should eat in order to stay healthy. And there are few topics where the evidence is so lacking in quality. It is also a topic that is besieged by gurus, cranks and supplement hucksters.

You need to beware of misleading titles.  Dietitians are good.  Nutritionists are sometimes  good.  But titles like ‘nutritional therapist’ and ‘nutritional medicine’ are usually warning signs of alternative therapists and/or pill salespeople.

Gary Taubes is a journalist, but he is quite an exceptional journalist.  His account of the importance of randomisation for the establishment of causality is one of the best ever and it was published not in an academic journal, but in the New York Times [1].  His book, The Diet Delusion, is in the same mould.  It is more complete and more scholarly than most professional scientists could manage.  Not only does it cover the literature right back to Samuel Johnson, but it is also particularly good at unravelling what one might call the politics of science.  And by politics I don’t mean the vast lobbying industry that has built up with the aim of selling you unnecessary supplements, but the politics of academia.

Obesity sounds simple.  If you are fat it is because you eat too much or exercise too little, right?  Well no, it’s not as simple as that.  For a start, it has been shown time and time again that low fat diets, and exercise, have small and temporary effects on weight.  The problem with diet and health revolves round causality.  The law of conservation of energy is an inevitable truth, but says nothing about causality.  It could imply that you get fat because you eat too much, or equally the causal arrow could point the other way and “we eat more, move less and have less energy to expend because we are metabolically or hormonally driven to get fat”.  The assumption that positive caloric balance is the cause of weight gain has predominated since the 1970s and “this simple misconception has led to a century of misguided obesity research”.

At the heart of the problem is the paucity of randomised trials, which are the only way to establish causality.   Those that there are have usually shown that diet does not matter as much as we are told.  Taubes concludes

“It does little good to continue basing public health recommendations and dietary advice on association studies (the Framingham Heart study and the Nurses Health Study are prominent examples) that are incapable of reliably establishing cause and effect.”

I think it can certainly be argued that the problem of causality has been greatly underestimated. We are warned constantly of the dangers of processed meat, on the basis of very unconvincing evidence [2].

This is one reason why we still know so little about the causes of obesity, diabetes and heart disease.  For Taubes, a major villain was the US nutritionist  Ancel Keys (1904 – 2004).  His
forceful advocacy of the low-fat hypothesis in the early 1970s, was, says Taubes, based on ignoring the many studies that did not agree with the idea.  It seems that the sort of citation
bias, recently described systematically by Greenberg [3], resulted in great exaggeration of the strength of the evidence.    

It is quite possible that there was rather more to be said for the Atkins diet than was apparent at the time.  The fact that Atkins was not a university scientist, that his views were extreme and that he was so obviously out to make a lot of money from it, gave him all the appearance of being yet another profiteering diet guru. He was dismissed by the medical establishment as a quack.  Taubes points out that conflict of interest cuts both ways.  Atkins’ sternest critics at Harvard were funded by General Foods, Coca-Cola and the sugar industry. It adds up to a sorry story of a conflict of vested interests and scientific vanity.

Taubes’ final judgement is harsh.  He quotes Robert Merton’s description [4] of what science is, or should be.

“The organization of science operates as a system of institutionalized vigilance, involving competitive cooperation”
In such a system, scientists are at the ready to pick apart .and assess each new claim to knowledge. This unending exchange of critical appraisal, of praise and punishment, is developed in science to a degree that makes the monitoring of children’s behavior by their parents seem little more than child’s play".

He then comments

“The institutionalized vigilance, “this unending exchange of critical judgment”, is nowhere to be found in the study of nutrition, chronic disease, and obesity, and it hasn’t been for decades.”

It took Taubes five years to write this book, and he has nothing to sell apart from his ideas.  No wonder it is so much better than a scientist can produce.  Such is the corruption of science by the cult of managerialism that no university would allow you to spend five years on a book [5].  I find all ten points in his summary convincing.  But his most important conclusion is that you cannot have any certainty without randomised trials. 

The business of nutrition is greatly at fault for not having put more effort into organising randomised trials.  Until they are done, we’ll never really know, and we shouldn’t pretend that we do.

1.   Taubes G. Do we really know what makes us healthy? New York Times 2007 Sep 16.[full text link]  [pdf file]

2.   Colquhoun, D. (3 May 2009) Diet and health. What can you believe: or does bacon kill you?.

3.  Greenberg, S.A.. 2009  How citation distortions create unfounded authority: analysis of a citation network.   BMJ ;339:b2680 [pdf file].

4.   Merton, R. K. Behavior Patterns of Scientists . Leonardo, Vol.3 1970; 3(2):213-220. From Jstor [or pdf file]

5.   Lawrence PA. The mismeasurement of science. Curr Biol 2007; 17(15):R583-R585.PM:17686424 [pdf file]  [commentary]

If length had allowed, there should certainly have been a reference here to Robert Lustig of UCSF. He is an academic nutritionist who supports the main thesis of Taubes’ book. See, for example, his 2005 review, Childhood obesity: behavioral aberration or biochemical drive? Reinterpreting the First Law of Thermodynamics [full
text link
]. Lustig’s slide show, The Trouble with Fructose is available in the NIH web site.

There are a couple of other articles by Taubes that are well worth reading. The Scientist and the Stairmaster Why most of us believe that exercise makes us thinner—and why we’re wrong. Gary Taubes, in New York Magazine, and We can’t work it out, in the Guardian.

You can see Taubes in action on YouTube, for example in “on Cholesterol and Science Practices“, and “on Carbohydrates and Degenerative Diseases“. There is also a video of Taubes on medical grand rounds at Dartmouth-Hitchcock Medical Center in June 2009. You can see Robert Lustig on YouTube too: “Sugar: The Bitter Truth“.

Follow-up

22 December.2009,  Unlike the serious questions dealt with in the Diet Delusion, this concerns merely another bit of the ubiquitous nutribollocks that crops up in the media,  While writing this I was listening to the excellent early evening news programme, PM, run by Eddie Mair, when a diet-related topic came up,  it was nonsense about how a cocktail made with vodka, cointreau, acai juice and pomegranate juice would not give you a hangover.  I suppose it was meant as christmas fun but  whenever I hear the words ‘antioxidant‘ or ‘superfood; I feel an email coming on.  It seems that Eddie Mair liked the fact that the email contained the words ‘quack’ and ‘codswallop’  because the next thing I knew I was asked to give an interview on next day’s programme.  The mp3 is here.

Recent Comments