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Monday, December 15, 2014

BMI, Obesity & mortality: three grand challenges

BMI, Obesity & mortality: three grand challenges

BMI (kg/m2) is one of the most widely used anthropometric measures and is virtually the sole criterion for judging obesity, its extent and its links to disease and mortality. When something is that widely used, there is a tendency to forget about any shortcomings in its use. In this blog I look at three aspects of BMI to remind one and all that in the BMI-obesity-mortality triangle, all is not rosy.

Challenge 1. How good is obesity at predicting body fatness.

It is important to recognise that the definition of obesity is based on a correlate of body fatness but is itself not a direct measure of human fatness. One study[1] has examined the relationship between % body fat measured using the technique of bioelectrical impedance and BMI in a large (13,601) sample of US adults. Using a statistical method of evaluating true and false positives, BMI was classed as “good” for men aged less than 60 years and as “excellent” for women of that age. For those above 60, the true sensitivity was classified as “fair” for men and again “excellent” for women. The authors note: “In our results, BMI showed an unacceptable low sensitivity for detecting body fatness, with more than half of obese subjects (by body fat measurement) being labeled as normal or overweight by BMI”.   Shorter people tend to be so because of shorter legs meaning that their trunk, the heaviest part of their body, contributes disproportionately to BMI compared to taller people. Indeed data exists to show persons with short legs can have BMI values that are 5 units above what they would be for persons of average height[2].

Challenge 2. Is the BMI-mortality the curve constant for age?

Conventional wisdom states that the relationship between BMI and mortality is U-shaped. That is, there is a minimal risk where BMI ranges from 20 to 25. On either side of this optimal range of BMI, obesity rates rise. They rise slowly in the initial deviation from this range and then they rise rapidly at BMI values below 18.0 or above 30. The U-shaped nature of the BMI-mortality link is often explained by the fact that at the lower end od BMI there are many smokers who are generally thinner that the average and also have a higher risk of disease. In 1983, the Royal College of Physicians (RCP) in London issued a report on obesity[3]. The report showed that the U-Shaped nature of the curve linking BMI and mortality is identical among “never smokers” and “smokers” (20 cigarettes per day). So the sharp rose in mortality at the lower extremes of BMI is not explained by smoking but may be explained by a higher percentage individuals who are light in weight as a result of some diagnosed or non-diagnosed disease.

The U-shaped mature of the BMI-mortality link is held to be universally true for both sexes and for all ages. But that is completely incorrect. The 1983 RCP report  looked at the link between BMI and mortality across ages. The rule that a BMI range for the lowest level of mortality was 20-25 held true up to the age of 50. For the next decade, mortality rose steadily as BMI fell below 22 and it rose again steadily above a BMI of 30. In between there was no rise in mortality with changing BMI. For those aged 60 to 69 years, the same steady rise in mortality below a BMI of about 22 was again seen but there did not appear to be any rise in obesity at any BMI above that value. When averaged across all ages, the conventional wisdom applied but above the age of 50, this was not the case. Two years later, researchers in the US confirmed that finding and they identified 23 other reports in the literature, which supported the notion that BMI should be looked at differently in different age groups[4].

Challenge 3. Is a higher BMI always bad ~ the obesity paradox.

Research conducted using US data gathered across three national surveys where weight and height were directly measured showed that the lowest risk of mortality was found to be in the BMI range of 25-30[5]. Now that was a direct challenge to conventional wisdom. This was true across all age groups and both in the total population and among non-smokers. The research also showed that the risk of mortality with obesity, fell with age. Indeed, among 70 year olds being obese increased the risk of mortality by 3% and being severely overweight, the in crease was 17%. Comparable figures for those in the age range 20-59 were 20% and 83% respectively. The obesity paradox had been born. Now it is a flourishing area of research. In 2013, the same team took a look at the global literature and ended up examining data from 97 studies, involving 2.88 million people with 270,000 deaths[6]. The same pattern was found. The nadir in the BMI-mortality link was found in what is deemed to be overweight with a BMI of 25-30. The “obesity paradox” holds true if we focus specifically on the disease most associated with obesity, namely diabetes. One study drew on the US National Health Interview surveys from 1997 to 2006 studied 74,710 subjects and divided them into those with or without diabetes[7]. Each of these was divided into quintiles (fifths) of BMI. For those in the lowest quintile of BMI, mortality was about 4.5 times higher among those with diabetes compared to those without diabetes. However, at the top fifth of BMI this figure fell to 1.7. In other words, as people with diabetes got fatter, they lived longer.  When looked at subjects who never smoked, the protective pattern of increasing adiposity remained. Many similar studies are appearing, almost all of which confirm the existence of an obesity paradox. So,

We can bury our hand in the sand and pretend that these challenges don’t exist or we can get together and try to design studies, which will help unravel these anomalies.

[1] Romero-Corral A et al (2008) Int J Obes 32, 959-966
[2] Garn S et al (1986) Am J Clin Nutr 44, 996-7
[3] Royal College of Physicians (1983) J Roy Coll Phys Lond 17, 3-58
[4] Anres R et al (1985) Ann Inter Med 103, 1030-3
[5] Flegal KM et al (2005) JAMA 293, 1861-1867
[6] Flegal KM et al (2013) JAMA 309, 71-82
[7] Jackson CL et al (2013) J Gen Intern Med 29, 25-33

Wednesday, November 26, 2014

Obesity ~ The McKinsey economic perspective

The McKinsey Global Institute produces a series of discussion papers funded solely by the McKinsey partners and very recently, they released a report entitled “Overcoming obesity: an initial economic analysis”. The report is divided into two main sections, one dealing with the economic burden of obesity and one dealing with the possible interventions to mitigate the economic costs of obesity. For anyone interested in the subject, I strongly advise accessing the PDF, which is available free[1].

The first point they note is that obesity does not appear to be correlated with a country’s wealth. Malaysia, Thailand and China have a much lower GDP per head of population than Hong Kong, Japan and South Korea and yet they have the same rates of obesity (5-15%). Equally, Japan, South Korea and Hong Kong have one-third the obesity rates found in Saudi Arabia, the US and UK (30-35%) and yet they share the same GDP/head/year. Developing countries have obesity rates that are just 25% that of developed nations but their rate of annual increase in obesity levels are much higher that developed countries (+90% v. +17%).

The report examines 14 major global problems which are largely man made or are amplified by human decisions. Top of the list is smoking with an annual cost of US$2.1 trillion. Armed violence, war and terrorism share joint first place with tobacco and in third place comes obesity with an annual cost which is just marginally less at US$2.0 trillion. The first two each occupy 2.9% of global GDP while obesity occupies 2.8%. Taking the UK as an example, the report shows that obesity costs the taxpayer a staggering stg £10 billion annually, which is 5% of the total National Health Service (NHS) costs. But they do express this figure differently with shocking effects. This stg £10 billion on obesity equals the combined costs of the UK police force, fire services, law courts and prisons!!!

In terms of tackling obesity, the report rightly argues at the outset of this section that: “Obesity is the result of a multitude of factors, and therefore no single solution is likely to be effective in tackling it. A range of interventions that encourage and empower individuals to make the required behavioural changes will be necessary. These interventions need to be systematic, not only aiming for an immediate impact on the net energy balance but also making sure that change is sustained”. Music to my ears! However, it is clear that despite the moanings and groanings of ministers about the terror of obesity, investment in prevention is abysmal. The report estimates that we would need a global investment of US$ 5 billion, which is just 0.25% of the global cost of obesity. The same percentage figure for road traffic accidents is 5 times that of obesity.

The report identified a total of 74 possible interventions, which they reduced into 18 groups and the list is as follows: Active transport; Health Care Payors; Healthy meals; High calorie food and drink availability; Labelling; Media restrictions; Parental education; Pharmaceuticals; Portion control; Price promotions; Public health campaigns; Reformulation; School curriculum; Subsidies, taxes and prices; Surgery; Urban environment; Weight-management programmes; Workplace wellness. The study examined over 500 research studies and they used the Level of Evidence System of the Oxford Centre for Evidence-Based Medicine. They have some caveats about their analysis and point out that this is the first in a series of reports on this topic. They word this reservation very nicely: “The conclusions we draw on an integrated response to obesity should be viewed as the equivalent of a 16th-century map of the world; some islands may be missing and the shapes of continents somewhat skewed, but it is directionally correct.”

If the 16 responses that are amenable to economic quantification were to be enacted in the UK, they would expect that this would halt rising obesity and indeed reverse the obesity prevalence by 20% within 5 to 10 years. They rank the impact of each response in a cost effective way using the standard expression of Disability Adjusted Life Years (DALY). The top three are (1) Portion control with a DALY value of 2,126, (2) Reformulation with a DALY value of 1,709 and (3) High calorie food/beverage availability with a DALY value of 1,137. Interestingly, they also examine how these rankings are linked to media coverage using UK data. It makes interesting reading. Portion control with a DALY value of 2,126 had just 182 media coverage while a 10% tax on high sugar high fat products with a DALY value of just 203 had over 930 press citations.

Thus far in the McKinsey obesity journey, the map tells us where we get most bang for our buck but most importantly, it tells us that ALL areas need to be simultaneously acted on to have any benefit. The day will come when flesh has to be put on some of these responses and here I have a problem. The top ranked solution is portion control and in reading the report there is discussion of how companies are going to move in this direction: Do they all do it together or will there be “leaders”? Now, this morning, I had porridge for breakfast and I determined how much porridge to put in my bowl and how much and what type) milk and sugar I’d put on the cooked porridge. For lunch I had home made soup and bread and I determined the size of soup bowl, the quantity of soup to consume, the number of slices of bread and the amount and type of spreadable fat to use on the bread. This evening, I’ll dine with my youngest daughter and my eldest granddaughter in an Italian restaurant and while I’ll have no control, more or less on portion size, I myself will decide on how much to eat and how much to leave. Regulating the portion size of snack bars is easy. Regulating the portion sizes majority of the foods we eat at home is an entirely different challenge. We need somehow to create an environment where large portion sizes are anti social. Taxes have played a huge role in tackling smoking but this was associated with an aggressive and well funded public health single-issue campaign against smoking. New data suggests that the anti-social aspect of smoking was every bit as powerful as taxes[2]. Taxes will be lees effective in directing food choice but energy intake can be reduced by adopting new social norms to serving sizes and eating behaviour in general. How to achieve this is the massive challenge. Smaller plates? Let’s put a tax on plate size!!!!!! Well done McKinsey.

[2] Kevin Callison and Robert Kaestner, Do higher tobacco taxes reduce adult smoking? New evidence of the
effect of recent cigarette tax increases in adult smoking, NBER working paper number 18326, August 2012.

Wednesday, November 5, 2014

Sugar: Bad science ~ Great headlines

 Just three weeks ago, the headlines of a popular British newspaper carried the banner headline on its front page linking fruit juice consumption with elevated blood pressure. It was based on a study reported in the generally well-regarded scientific journal Appetite and was conducted by researchers in Australia[1]. The sample was small, just 146 subjects and their diets were analysed using a food frequency questionnaire. The authors created three groups according to their intake of fruit juice: “Rarely”, with fruit juice intake ranging from 0 to less than 3 times per month, “Occasionally” ranging from once per week to 5-6 times per week and “Daily” corresponding to once per day to more than 3 times per day. They examined blood pressure using two techniques that measure central blood pressure and brachial blood pressure. The authors found no statistically significant effect of fruit juice consumption on brachial blood pressure but they did find a statistically significant effect of fruit juice intake on central blood pressure (systolic only). The authors in their discussion note that this is the first study to examine the link between fruit juice consumption and hypertension and it should be noted that they do associate fruit juice intake with fructose intake. They go on to say: ”These findings are important as there is a common perception that fruit juice is healthy” and they continue, thus: “Thus, frequent fruit juice consumption may be contributing to excessive sugar intake, typical of the Western population, exacerbating the prevalence of hypertension.”

Now lets pause here for a minute, because this is quite a sensational claim. The authors have not examined total sugar intake in their study so they themselves cannot imply that higher fruit juice intake is associated with higher sugar intake. What about sugar from the sugar bowl, from jams and preserves, biscuits and cakes and of course soft drinks? In the absence of data on total sugar intake, the authors can conclude nothing whatsoever. The authors never mention this fact when they consider the limitations of the study. Rather, they regret that they were not able to statistically control for “total energy intake or total calories” (the same thing by the way). But they were able to control for weight height and other potentially confounding factors. Why could they not control for energy intake? To fail to report total energy intake and the fraction of that intake contributed by total sugar and added sugar is unfathomable in terms of scientific rigour. It renders this paper utterly useless and it casts a shadow on the editorial process of the journal where it was published. But it made great headlines and no doubt the Daily Mail story was carried around the world to warm the cockles of the beating hearts of the “sugar is toxic” school of thought.

Now contrast that paper with one published about the same time by a consortium led by David Jenkins a Canadian based world leader in the field of diet and health[2]. This group conducted a systematic review and meta analysis of studies, which have measured actual fructose intake and followed the subjects up for many years to monitor the development of hypertension. They identified 3,749 scientific papers with the words “fructose” and “hypertension” in the titles and immediately scrapped 3,723 because they were animal studies, cell studies, case studies, reviews rather that actual studies and so on. Of the 26 articles remaining, 25 were omitted because they had inadequate end-points (14), were a non-prospective (follow-up) cohort (7) or did not disclose total fructose intake (3). Theses omissions were all based upon strict rules that are internationally regarded as the “must follow” rules of systematic reviews. That left them with just three studies. However, these were very big studies, which involved 223,230 subjects who were perfectly healthy when recruited at baseline. They were followed up for an average of 11 years and 58,162 went on to develop clinical hypertension.  The subjects were categorized in to (fifths) quintiles of fructose intake. The authors found absolutely no evidence that the greater the quantity of fructose consumed from the lowest to the highest fifth was in any way associated with hypertension. The statistical models included all known confounding factors.

It should be noted that all three of the above papers were in the literature for the Australian group to go and find but apparently, they did not. The “sugar is toxic” die-hards will remember their study. But the scientific world will remain far more impressed by the Jenkins systematic review.

[1] Pase, MP et al (2014) Appetite 84, 68-72
[2] Jayalath VH et al (2014) J Amer Coll Nutrition, 33, 328-339

Saturday, October 4, 2014

Sugar, the brain and self control

Brian Wansink of the University of Cornell, in his excellent book “Mindless Eating – Why we eat more than we think[1]” describes many experiments from his laboratory where food intake is found to be quite often “mindless”, that is, the consumption of food occurs without any real thought as to the reasons for either starting or stopping eating.  Here is a simple example. Bright MBA students are offered a chance to watch the Super Bowl in a bar where soft drinks are free and where the students can go and collect as many chicken wings as they like as often as they like and enjoy the game with their friends. The bones get chucked into a bowl on the table. They are absorbed in the game and so they don’t notice that for half the tables, the bowls of chicken bones are emptied regularly throughout the evening. For the other half, the bowls fill up with chicken bones. Those in the latter group whose bowls were not refreshed ate just under 30% less chicken wings than those who had their bowls refreshed. The latter were into mindless eating but for those whose bowls piled up with chicken bones, they had a visual cue to halt mindless eating. Many, many other marvellous examples are to be found in this excellent book, which everyone in food and health should read.

The opposite to mindless eating brings us into the sphere of self control which seeks to override impulses and habits and it represents a conscious and thus effortful form of self-regulation involving the prefrontal cortex, that part of the human brain that utterly distinguishes us from all other species including our nearest primate relatives.

In some respects, this mindless and mindful eating pattern ties in with the theory of decision making proposed by the Nobel laureate in economics, Daniel Kahneman in his book “Thinking fast and slow”[2]. He identifies two distinct systems in the brain for decision-making. System 1 “operates automatically and quickly, with little or no effort and no sense of voluntary control” (Mindless eating?). System 2 “allocates attention to the effortful mental activities that demand it. The operations of System 2 are often associated with the subjective experience of agency, choice and concentration” (Self control or mindful eating?). Kahneman sees System 1 as the default where most decisions are made and system 2 then operates to support System 1. It’s fascinating, relevant but let’s turn to nutrition.

The brain occupies about 2% of our body weight and for an adult, the brain accounts for 20% of total caloric intake. It is a majorly expensive organ in terms of energy just as super-computers are also massive energy consumers. Under normal circumstances, the brain only uses glucose as a fuel and it will slightly deviate from this after a fast of a day or so. Now when we are sitting around with friends having a coffee and chatting about life and loves and whatever, the amount of glucose by the brain is at its lowest, ticking over liked a car in park or neutral. Now give the subjects a mental task, which requires a serious usage System 2 decision-making and the brain, starts to consume significant amounts of glucose. Now some time after completing this demanding mental task, give the subjects what is known as “the marshmallow choice”. You can take a marshmallow now or you can hold on and restrain yourself and then have two marshmallows later, “smaller and sooner” as opposed to “larger but later”. How does the mental task influence self-control?

Lets turn to some experiments with human volunteers[3].  Participants were asked to watch a 6-minute video. One group watched it without any interference in a relaxed manner. In the second group, certain stimuli appeared on the screen and this required an extra mental effort to follow the video. For the first group, blood glucose levels didn’t change. For the second group, their blood glucose levels fell. Numerous other studies support this. Now lets go one step further and have two limbs to the experiment. Participants were first exposed to a thought-suppression task such as suppressing frightening thoughts of a white bear. Another group were not given any thought-suppressing tasks (control). The theory here is that by forcing the brain to use System 2 (worrying about a white bear), glucose would be used by the brain in significant quantities. Half the subjects were given a glucose drink and the other half relaxed reading magazines (the groups were separate). Now all subjects were given a task, which was quite frustrating and actually impossible to achieve. Those who were given the thought-suppressing tasks imagining a white bear gave up quicker than the control group. Their self- control was cut short by the prior use of glucose by the brain. However, the glucose drink obliterated this effect. The glucose drink replenished the brain’s glucose supply and now they fared as well as those that did not have any thought-suppressing exercises. Again, the literature abounds with such examples. In summary, forcing subjects to focus on some mental task uses up blood glucose and subsequent self-control falls. However, drinking glucose reverses this.

There is a final twist in the tail from a recent paper in the Proceedings of the National Academy of Sciences[4]. Subjects were classified according to their beliefs that will power is either a limited trait and easily depleted (limited resource belief) or that will power is plentiful and not easily depleted (non-limited resource belief). The subjects then consumed a drink, half of the drinks contained sugar and half an artificial sweetener. The subjects were then given a demanding task such as deleting the letter “e” from a text but with rules about which ones to drop out and which ones to leave in. This required a lot of glucose consuming brain concentration. Then they were given a standard psychological test  (The Stroop test), which measures self-control. Among those who believed that will power was plentiful, the sugar drink had no effect. Among those who believed that will power was a limiting and easily depleted, the glucose drink did the trick. They performed better in the self-control test than those given the drink with the artificial sweetener.

All in all, these data tell us that cognitive and mental capacity can be readily influenced by exhaustive mental tasks. This causes a decline in the brain’s supply of glucose. The net effect of that deficiency is to reduce self-control. Apparently, among those who believe that self-control is weak and limited, a sugary drink will restore mental performance. So, the next time you hear some guru bashing sugar, remember that glucose alone is the fuel of the brain and that that fuel is precious for every day decision making.

[1] “Mindless Eating – Why we eat more than we think” by Brian Wansink and published by Hat House, London. Available on Amazon
[2] “Thinking fast and slow” by Daniel Kahneman, published by Penguin and available on Amazon
[3] Gailliot MT & Baumeister RF (2007) Personality and Social Psychology Review,11, 303-7
[4] Job V et al (2013) PNAS, 110, 14,837-42