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Tuesday, May 17, 2016

My new book: Ever seen a fat fox ~ human obesity explored

Ever seen a fat fox ~ human obesity explored: Chapter outline

            Preface: The preface starts with two quotations from the UK Foresight          Report on obesity which clearly spells out the complexity of obesity and    as a result the need for obesity to be tackled through a multi-level and           multi-disciplinary approach which must be adequately funded by central         government and the book argues many times that this simply does not          occur. The single largest UK investment programme on obesity has a   budget only a fraction that of the annual spend of the Royal Society for the   Protection of Birds. The preface brings the reader through the overall     book plan and gives the reader some idea of what to expect by the end of     the book

            Chapter 1: Ever seen a fat fox. We share an enormous amount of our            genes with the animal kingdom but, with the exception of the hand of      man, no other species gets fat and remains fat for life. This chapter explores the uniqueness of human culture, our highly sophisticated communication system, the advent of a quasi-religious and mystical approach to modern food and the phenomenon of human ambivalence to hazards and why that differs between threats such as Ebola and obesity. It       deals with economic growth and the global nature of obesity and how obesity follows affluence. It ends with an exploration of the pursuit of happiness and how obesity prevention programmes must take account of the daily concerns of ordinary people in their ordinary lives. None of these issues bother the fox. Obesity is uniquely a human condition.

Chapter 2: Obesity and health - measurements and metrics. Today, obesity is measured across a range of values for what is termed Body Mass Index (BMI; weight in kilograms divided by the square of ones height in metres; kg/m2) and can be rapidly calculated using many Internet based tools. Few people know where this range came from and the first part of this chapter outlines the historical basis for the widespread adaptation of BMI as a quick and easy measure of fatness. However, the chapter does go on to point out that in fact BMI is a crude measure of body fat and when it is used, it must be recognised as such. A second major part of this chapter goes back in time to a 40-year-old report of the UK Royal College of Physicians, which showed that BMI is a poor mark of mortality risk in those over 50 years of age but is a strong predictor of risk among younger persons. This is an example of how an aspect of BMI is far more complex that is popularly portrayed. Finally, we turn to a very recent challenge to the exact optimal BMI to limit mortality drawing on a large body of new data from leading epidemiologists. Their argument is that the ideal weight for minimizing mortality is in fact, that of the present range defining overweight. This controversy, known today as the obesity paradox, has caused much dissention in the field of obesity epidemiology. The present books favours a conservative view pending urgent collaborative effort to resolve this issue

Chapter 3: Human obesity – old and new. This chapter is prompted by the school of thought, which argues that since obesity is an entirely recent phenomenon, its cause must also be recent and thus such recent causes must define solutions to the problem. The chapter rebuts this by going back in history to the Graeco-Roman era, through the age of renaissance to more modern times to show that whenever and wherever man became affluent, we had obesity. The chapter concludes with an examination of actuarial data from the insurance companies in the 19th century who already had linked the risk of diseases such as cancer, heart disease, liver disease and diabetes to increased body weight. The chapter gives evidence to show that obesity was come in waves with surges and lulls drawing on military based records of such data, back to prior to the US civil war or to immediate post war Denmark.

Chapter 4: The human food chain – old and new. There is a widespread belief that the diet of today is very recent in origin in terms of the foods available to us. This is challenged in this chapter. Six milestones are explored which mark the evolution of the modern diet: fire, cooking, agriculture, innovation and invention, Industrialisation and the high street. Sugar, bread, cakes, biscuits, sausages, lemonade, booze, fish and chips, hamburgers, popcorn and the like are hundreds of years old. What is new is the high street and with it the growth of large supermarkets with powerful purchasing power to drive down food prices together with the mass mechanization of agriculture, food production storage and distribution. Blaming the modern food supply is popular but not necessarily always productive. Many everyday foods do not have an international corporate provenance: fruit, vegetables, salads, meat, poultry, fish, cheese, bread, oils, yogurt and the like.

Chapter 5: The fashion of culpable calories. According to the media, fed by many very poorly qualified experts and by some publicity-minded scientists, sugar is now the downfall of the human race and fat, once the villain, is now seen as the saviour. All of this is utter nonsense. To begin with, most of the data used in this debate relies on “associations” as observed using epidemiological data. It also relies on extreme dietary studies with rats and mice. However, when put to the acid test of human experimentation, such assertions simply melt away. Equally this chapter refutes the claim that nutritionists are forever changing their advice. Minor adjustments have been made as new data emerge but largely, such advice has remained largely unchanged in 50 years. It is the media hype and fashion that changes in a cyclical phase.

Chapter 6: The nature versus nurture debate.  Modern biology is dominated by genetics and the search for the genetic basis of many diseases including obesity. There are some established conditions where the deletion of a single gene leads to obesity but such conditions are rare. For most people who are overweight, any role of genetics will feature a multitude of genes. The most compelling case for a role of genetics in weight gain and obesity comes from the study of identical and non-identical twins. The former share an identical genome while the latter does not. Among children, both share a similar home environment. Geneticists can use twin data to ascribe the differential contribution of the genetic dimension and the home environment. A vast body of evidence shows that obesity has a heritability of about 75%. That means that in an obesity-promoting environment, similar to that which is found most developed economies, those who go on to develop obesity have a high genetic propensity to do so. In contrast, those who live in such an environment and who maintain a normal bodyweight range are genetically protected from developing obesity. This genetic control of weight might operate at any one of a multitude of possible control points.

Chapter 7: Regulating food intake - the eyes have it. If we place the focus of the regulation of food intake in the animal world, we emerge with a swathe of neural networks, metabolic pathways and candidate brain hormones. Whilst these unquestionably operate in man, we regulate food intake very differently. In general, and especially at home, we clean our plates. Thus, we know in advance exactly how much we intend to eat before we begin our meal.  And we might not wish to continue to dessert but might feel that it would be bad manners not to accept one’s host’s hospitality. Manners might also deter us from asking for second helpings. Researchers have shown that we are more likely to eat familiar foods and by and large we are the only species that express disgust at other groups dietary habits. We have religious constraints on food choice and also health constraints such as allergies. We eat at specific times of day irrespective of our state of hunger. All in all, we normally eat within cultural constraints and only veer toward animal behaviour when food supplies significantly diminish.

Chapter 8: Fitness and fatness. According to the WHO, physical inactivity is the 4th leading cause of death globally, one place ahead of obesity. Physical activity is in fact the orphan of the bodyweight and health debate. The direct medical costs of physical inactivity are estimated at $24 billion and the overall medical costs are estimated to be $ 76 billion per annum. To put that into perspective, the annual budget for the FBI is just under $9 billion, that of the CIA is about $44 billion and the Department of Homeland Security spent just $66 billion in 2011. The bottom line is that to be lean and sedentary is much worse in terms of health than being fat and fit. Physical activity helps to reduce most of the main adverse effects of obesity: high blood pressure, type 2 diabetes and adverse blood lipid profiles. Physical activity in work has been shown to fall dramatically with each new labour-saving device. The traditional US Amish communities, who shun technological inventions, take around 33,000 steps per day as opposed to the average US citizen who takes just over 7,000 steps daily. Therein lies the problem. The solution is obvious: Get moving!

Chapter 9: A miscellany of matters. For every story that evokes a “wow” factor in the media, there are many that go un-noticed, falling just outside the media radar. Equally, there are areas, which the media are beginning to pick up on with varying levels of supporting scientific evidence. This chapter looks at four such areas. Maternal nutrition from conception to two years of age (the first 1,000 days) can play a very large role in shaping adult obesity. It is an area utterly ignored by policy makers.  The Human Rat Race means that families are absorbed in a highly competitive work environment with high mortgages absorbing almost every cent. Healthy eating is high on the wish list but time and the need for family peace don’t always make healthy eating an automatic option. A third area of interest, one increasingly hitting the headlines is the human gut microflora or in modern-speak, the “microbiome”. This is an area of remarkable over-hype when its impact is extended beyond the gut to other areas of the body with quite incredible views on its power from mental health to gum disease. Finally, there is the highly appealing but nonetheless mythical notion of food addiction which scores very highly on the “sugar is evil” agenda but which is utterly lacking any scientific rigour.

Chapter 10: Obesity; the fears and the phobias. This chapter examines the phenomenon of eating disorders – anorexia nervosa, bulimia and binge eating disorders. It looks at the prevalence and the outcomes of such disorders and their treatment and management. These conditions largely affect teenage females and several case histories are examined including the experience of Lady Diana and other celebrities. It also looks at the very widespread stigmatisation of fatness, which sees fat people as lazy, sloppy, unreliable, dishonest, untrustworthy and selfish, among many negative attributes. These views are held even by children and amongst fat children and all streams of health care workers also hold them. This stigmatisation leads to disadvantage in employment, promotion and job security. The first step in combating fat stigmatisation is to recognise the problem and to look beyond body shape into the minds and hearts of the overweight and obese. Compassion, care and understanding must lie at the heart of any move to reduce fatness stigmatisation.

Chapter 11: Obesity – politics, players and ploys. Many groups holding disparate views shape obesity-focused food and nutrition policies. These groups include non-governmental organisations (NGOs), which are frequently single-issue NGOs, international agencies such as the World Health Organisation, the scientific community where quite differing views frequently exist, the food industry, the media, leading scientific journals and politicians. This chapter explores the acquisition of different viewpoints by these players and examines how they use data to foster their own viewpoints. Few come out smelling of roses but the most worrying of these shortcomings is the repeated published reports of the failure of the WHO to adhere to the highest level of scientific rigour in formulating what become globally, powerful opinions.



Chapter 12: Weight management – the personal perspective. Losing weight is easy. Keeping it off isn’t. In fact the 5-year relapse rate for weight re-gain is about 90%. Thus the present chapter opens with advice on considerations that must be taken into account before someone makes a commitment to weight loss. Should they pursue a weight loss goal, this chapter looks at three books written by leading US academics. The first (Mindless eating) focuses on the food environment and shows how visual cues can give us feedback as to when to start and to stop eating. The second (The step diet) outlines how physical activity can contribute to weight loss and particularly the management of weight loss. The third (The volumetric diet) explains how we can reduce caloric intake using low energy dense dishes. All three books build on high quality peer reviewed research.

Chapter 13: Weight management – the national perspective. The Nuffield Council on Bioethics is an independent think tank on ethics in the biological sciences and this chapter draws on one of its publications: Public Health – Ethical issues. A key recommendation of this publication is that public health intervention should follow a series of intervention steps, which is referred to as the intervention ladder. As we rise up the ladder, we need increasing evidence at two levels. Firstly, we need evidence that the intervention is likely to work. Secondly we need to set in place a series of measures to ensure that the intervention, once implemented, is successful or otherwise. A tax on fizzy drinks might be proposed albeit on weak enough evidence. But how would we measure success: a reduction in the % of consumers of fizzy drinks? : A concomitant reduction in caloric intake or weight intake? This chapter explores all levels of intervention and then focuses on governmental investment, particularly, financial investment.

Chapter 14: The way forward. From time to time, the prestigious journal, The Lancet, publishes a series of invited papers on a topic, with the direct intention to inform policy makers. The most recent series of 5 excellent papers is characterised by the absence of the word “budget”. In this writers view, until governments set out sizable budgets to finance independent obesity and physical activity agencies, which are independent of government, not part-owned by a multitude of single issue NGOs and which are allowed to take a long term view, we might as well whistle Dixie at the problem. Today’s largely NGO driven national policy issues are regulatory: Ban, abolish, license, restrict, tax and so on. Such top-down initiatives may be needed but must be coordinated properly and must be evidence based. What is largely missing from the agenda is the bottom up approach. Where comprehensive multi-stakeholder initiatives to reduce particularly childhood obesity have been tried, they have been found to be successful but only with one key word dominating this policy approach: investment. Without investment and without coordination, it is hard to see serious inroads into this huge problem being made.


Sunday, April 24, 2016

Diet, genes and Harvard conservatism

{My new book "Ever seen a fat fox ~ Human obesity explored" which has a chapter and section on diet and genes is due out mid May}
The Harvard School of Public Health has a recent web article on genes and obesity bearing the somewhat negative title: “Genes are not destiny” [1]. From my standpoint, this review is in fact defensive of a School where genomics appears to be low on their nutrition research agenda. This brief review of the Harvard position is written by a blogger who works both in public health nutrition but also in molecular nutrition.

The overview (hardly a review) begins by pointing out that obesity conditions linked to a single gene defect such as the Prader-Willi Syndrome are utterly rare. Equally, common ordinary everyday obesity is linked to so many genes that looking for one is like looking for a needle in a haystack. However, needles can be found in haystacks and we now know that high blood pressure is dramatically reduced in individuals marginally deficient in the B-vitamin, riboflavin, when given dietary riboflavin supplements but this applies only to those carrying a single variant of a gene we all have, the natural variant of the folic acid-related FTHFR. That variant isn’t rare. One in 10 of us carry it[2]. So lets not throw the baby out with the bath water as they say.

  Equally, the web article goes on to make the case that modern gene analysis technology allows us to explore how multiple sets of genes might explain common obesity. The more such complex sets of genes explain obesity, the fewer people we find with such a unique blend of genes and even at its best, this technology can explain only a few percentage points of the obesity problem. So far I am in full agreement with the Harvard team and I remain somewhat in agreement when they write:

“So if our genes have stayed largely the same, what has changed over the past 40 years of rising obesity rates? Our environment: the physical, social, political, and economic surroundings that influence how much we eat and how active we are. Environmental changes that make it easier for people to overeat, and harder for people to get enough physical activity, have played a key role in triggering the recent surge of overweight and obesity.”

Its here I start to divert from the Harvard dons’ views. According to the US Center for Disease Control[3], about 1 in 3 adults is classically obese while the same figure for children (2-19 years) is 1 in 6 (35% and 17% respectively).  The figure rises if we consider overweight but obesity is the sharp end of the problem in the Harvard analysis. Now if 1 in 3 US citizens are obese, then 2 out of 3 are not. They share as stated above, the same “environment: the physical, social, political, and economic surroundings that influence how much we eat and how active we are”.

So why isn’t everyone obese? Why some, not others. The answer is of course genes and we’ve known this for years. The Harvard review pays simple lip service to twin studies, the extensive literature on which tell us that obesity is about 70% heritable (only 20% in non-identical twins who do not share an exact genome as identical twins do).  In their simple reference to twin studies, the Harvard Dons reveal a deep prejudice when they write:
“The strong correlation for BMI between monozygotic twins and its attenuation with lesser degrees of shared genes suggest a strong genetic influence on BMI. However, this conclusion is based on the assumption that identical and fraternal twins have the same degree of shared environment-and it’s an assumption that may not hold in practice.”

The literature is peppered with outstanding scientific papers, old and new, which this overview sweepingly ignores. They completely fail to refer to the studies of twins raised apart for periods of almost 50 years in radically different environments and still showing an obesity heritability of >70%. They completely fail to refer to metabolic studies where identical twins were subject to 1000 additional calories per day[4] or a reduction in caloric balance through bouts of intense cycling[5]. Take for example the former. Some twin pairs showed a dramatic gain in weight with the extra calories while others didn’t. Different genomes predispose more or less to obesity. However, whatever one identical twin did, the other followed exactly. With weight loss experiments the same conclusions held.

In summary, we do know of some instances where a very common single gene variant can determine dietary responsiveness to a complex phenotype such as high blood pressure. We do know that identical twins show a 70% heritability of obesity (this exceeds the heritability of height, alcoholism and depression for example) and we know that identical twins raised apart for very long periods also show a very high obesity heritability[6]. Metabolic studies also explain variation in obesity heritability both between and within identical twin pairs. So, the case for optimism is huge and not so futuristic, as the Harvard dons would suggest.
One of the main flaws in the diet-obesity-gene link is the constant belief that it is to reductionist biology that we must turn to understand this problem. Metabolic pathways of fat and carbohydrate metabolism including fat cell, liver cell and muscle cell biology dominate. For me, the future is the genetics of food choice. Why are some people sensitive to the external cues to food intake – its sight, smell, ambiance, availability, time of day, etc? Why are some apparently more self restrained, less sensitive to genetic cues? Applying advanced neurobiological techniques to study neurobiological determinants and responses to food cues are the start.  I would then move to twin studies to rank the heritability of such neurobiological indices of appetite. In time I’d find more and more examples of heritable neuronal regulators and her I’m talking complex neuronal patterns. I don’t need to go to genes at this stage.  Moreover, I’d be looking not for determinants of individual behaviour but membership by individuals of clusters of neuronal networks as we currently apply to metabolomics.



[1] http://www.hsph.harvard.edu/obesity-prevention-source/obesity-causes/genes-and-obesity/
[2] Mahmud N et al (1999); Gut 45:389-394 

[3] http://www.cdc.gov/obesity/data/index.html
[4] Bouchard, C et al. (1990) ‘The response to long-term overfeeding in identical twins’. The New England Journal of Medicine, 322:1477–82.
[5] Bouchard, C et al. (1994) ‘The response to exercise with constant energy intake in identical twins’. Obesity Research, 2: 400–10
[6] Stunkard, A. J et al. (1990) ‘The body mass index of twins reared apart’. The New England Journal of Medicine, 322: 1483–7.

Sunday, March 6, 2016

Salt, health and nutritional dogmatism

Salt may be a health issue now but the two most famous salt wars involved the City of Perugia versus Pope Paul III over a salt tax introduced by the Vatican in 1540 and then the Mexican-US salt wars or El Paso salt wars of 1877 over ownership of salt rich lakes in Texas. Today’s salt war is fought on the plains and hills of public health nutrition and is put under the microscope in a series of papers in the International Journal of Epidemiology. The central paper, from researchers at Boston and Columbia Universities, examines the objectivity of both camps in this public health feud[1].

It began with a search of the scientific literature for all reports relating salt to health. A total of 269 such reports were found of which two thirds were simply comments or letters in learned journals, a quarter were primary studies in which the hypothesis of a salt health link was directly tested in humans and the remaining 9% were either guidelines or reviews of primary data  (systematic reviews). Of this body of evidence, 54% supported a link between salt and health, 33% were contradictory of such a relationship and 135 were inconclusive.

The authors used this large data set to answer a number of questions. The first was to analyse the data to ascertain if a bias in citation of scientific paper existed. By that is meant the following: Is an author who supports one side or other of the hypothesis more like to cite other studies supporting their stance and less likely to pay attention to studies which are at variance with their stance. The answer to that question is emphatically, yes. Those supporting the salt health link were twice as likely to prefer to cite similar supporting articles. Among those who contradict the salt-health hypothesis, they were three times more likely to cite contradictory than supportive papers and among those who were inconclusive, the bias factor was all of 15 fold. What this means is that scientists in this field are very definitely not objective in their view of the problem and presumably its solution. A second question was the extent to which the literature is dominated by a small or large body of papers. In fact, the authors found that a small number of authors and a few reports do, in fact, dominate the debate. Thirdly the authors sought to see if there was consistency in the selection of primary research data. In fact there wasn’t. Primary data, which are the hub of objectivity, were selected according to the prevailing bias of each camp.

John Ioannidis from Stanford University was asked to not only write a comment but to seek similar comments from those in the field[2]. He immediately encountered the dogmatism that dominates public health discussion. One invitee who declined to add a commentary wrote thus: “ the paper ….is rubbish…there doesn’t seem to be any realization that the majority of those papers that are against salt reduction are funded by the food or salt industry, just like the tobacco industry did (or still does for that matter) for cigarettes….I wouldn’t have anything to do with it.” This belief that scientific bias is a function of industry funding is very naïve. Those who live in the EU will be familiar with the requirement in the majority of research funding, that industry involvement is a must. Without it, the grant doesn’t even get to review. The logic is that such research will generate knowledge, create jobs and lead to economic growth. “Blue skies” research is funded with no industrial requirement but this is a small fraction of the research spend. Society makes the rules and scientists play the game according to those rules.

The philosopher Thomas Kuhn understood the way science works. He pointed out that it exists as “normal” science or “revolutionary” science. Revolutionary science is a rare occurrence such as the discovery of the double helical nature of DNA and its transforming effect on our knowledge of cell division. Normal science is the antithesis of revolutionary science and it utterly dominates the scientific landscape. So scientists “defend” the paradigms of normal science and continue to do so until, from nowhere, emerges some new revolutionary finding, which, forever, changes the science landscape.

  • In the salt and health war, honest scientists have for one reason or another looked at the landscape and decided to support or contradict the thesis. Or did they? Is it possible that they first opted for one side or the other, and then sought the scientific basis to support these views? The Nobel Laureate in economics Daniel Kahneman would argue the latter. He points out that our brain operates the decision making process in two systems.
  • System 1: Fast, automatic, frequent, emotional, stereotypic, subconscious
  • System 2: Slow, effortful, infrequent, logical, calculating, conscious

System 2 decides first on which side of the salt (and general health) debate we reside. System 1 now bolsters this with analytical data.


Ioannidis argues that the scientific morass of salt and health cannot be resolved by reviewing the existing data no matter how fancy the statistical approach of that review might be. Primary data, which studies real human beings in real life settings, are what counts. As he points out, the design of real primary studies can be such as to more likely to lean in one direction than another.  The loser is Joe Soap who eventually does what the US electorate is presently doing. They will cry: ”A plague on both your houses” and go their own way. Scientific dogmatism is destroying science. Dissent is the oxygen of science and to belittle it and its proponents, as “industry hacks” is sad. These days the noisiest and most vociferous media friendly scientists win.


More on this in my new book: ”Ever seen a fat fox ~ Human obesity explored” due out in early May




[1] Trinquart L et al (2016). Why do we think we know what we know? A metaknowledge analysis of the salt controversy. Int J Epid, February 17th
[2] Ioannidis JPA (2016) Commentary: Salt and the assault of evidence. Int J Epid February 17th