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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

Thursday, February 4, 2016

Sugar tax : some hard questions

A sugar tax, or more correctly, a soda tax, is the talk of the town and the darling of the media these days. Far be it for me to spoil the party, but I’d like to ask some questions of the proponents of a soda tax to try and get the full picture and not just the sloganistic headlines.

#1. Given the extensive data that we have to hand on national patterns of food and nutrient intake, all of which can be readily linked to bodyweight or body mass index (BMI), where can I find the relevant report that shows that, of all the foods that might be taxed to curb obesity, soda is the clear target?

The simple answer is that in the myopic propaganda on soda tax, no such extensive analysis exists that I know of. So, we are not taxing savoury snacks, fast foods, sugar or chocolate confectionery or booze. Just soda. And we are doing so simply because it is now a global fashion. Of the foods just mentioned, how do policy makers know their average contribution to energy intake, the % of the population who consume them and the intake of these foods among consumers only? How do policy makers compare econometric models for the application of a tax on such foods? The answer to both questions is that such data has not been gathered and therefore is beyond policy makers. They must just trust the soda tax lobby.

#2. Does a soda tax have universal or limited benefit?

The answer is that only those who consume sugar-sweetened beverages feel any putative impact of a soda tax.  In Ireland, that means that 60% of the population might benefit. So 40% of the Irish adult population is unaffected. Nobody on the planet can possibly argue that obesity resides solely among those who consume sugar-sweetened beverages. So the excess weight problem of those who are non- consumers of sugary sodas is ignored. Politicians, please note how many votes you are ignoring in your zeal for soda taxes as presently formulated.



#3. What would be a measure of success of a soda tax?

There are many end points that could be chosen to measure the success of such a tax and in this blogger’s view, policy makers have right to know (a) what would constitute a success and (b) within what time frame. The most likely measure to be proposed is a fall in the purchase of sugary sodas. Since sodas account for a fraction of sugar intake (calculated by my students as 8% of added sugars for the average of Irish consumers) one would not expect to see a dramatic fall in energy intake arising for a soda tax. Moreover, all of the biological evidence at hand suggests that at least some, if not most, of this small drop in energy intake would be compensated for by increased energy intake from some other food sources. Since the purpose of the proposed soda taxes is to combat obesity, do policy makers not have the right to ask the question: “Notwithstanding your excellent data on altered purchase patterns of soda post the tax, could you please give me data on (a) energy intake changes and (b) BMI changes”? The short answer is that such data are not likely to be forthcoming because the focus must be on those who, at the time of the introduction of the tax, were consumers of sugary sodas. There is no point in national average values since not everyone is equally affected by these taxes. As regards time frames, the policy-makers are never told when would be a fair time to ask the hard questions of success or otherwise.

#4. Is there some unwritten and unuttered expectation among the pro-soda tax lobby, that this is just the start and other putative contributors to obesity will soon be targeted as taxable candidates?

One would be naïve not to believe that next we’ll have fast food or sugar and chocolate confectionery etc. as targets for taxation. If that is the case, might it be too much to ask for some honesty here and to re-run all the existing econometric models in which all possible future combinations are included? What combinations would be least regressive? What combinations would have the greatest impact on energy intakes taking all reasonable consumptions into account? What might the economic elasticity of demand look like for various combinations of taxable food categories? In this bloggers view, multiple taxation strategies are just around the corner. This follows logically from the view of the high priests of public health nutrition that the regulatory environment is the way forward, based on prior experience with seat belts in cars, to tobacco, to alcohol and so on. For sure we need a regulatory environment but we also need a bottom up community involvement, one that is well resourced financially, is multi stakeholder driven and which takes a medium to long-term perspective. An example of this is EPODE community projects on obesity (http://epode-international-network.com)

#5. If sugar intakes fall as a result of single or multiple taxes with a sugar focus, what is the likelihood that the % energy from fat will rise and does that not pose a serious question that merits an answer before we go down the avenue of food taxes to tackle obesity?

There is a phenomenon known as the sugar-fat seesaw. It is poo-pooed by the sugar tax lobby as some odd artifact of data analysis or whatever. The hard experimental data say otherwise. If you covertly or otherwise remove sugar calories from the diet, they will be replaced in part or total by fat calories[1]. The energy density of the diet will rise (fat has 2.25 times the calories of sugar on an equal weight basis) and energy intake will increase among the many who are susceptible to such high-energy diets [2],[3].

NOTE: These are just some of the arguments that will appear in my new book, due for release in April: ”Ever seen a fat fox: Human obesity explored”



[1] Markey O et al (2015) Energy compensation following consumption of sugar-reduced products: a randomized controlled trial. Eur J Nutr. 2015 Sep 9. [Epub ahead of print]
[3]  Hall et al (2015) Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab. 2015 Sep 1;22(3):427-36


Thursday, December 17, 2015

Traditional Chinese Medicine: Daring or dangerous


Today’s food and medicine industries are losing trust with consumers who regrettably are misled by TV an endless queue of utterly unqualified food and health gurus who promulgate pure unadulterated nonsense as to the shortcomings of modern food and medicine and the wonders of specific foods and traditional medicinal remedies. Let’s start with food remedies. Manuka honey is a honey produced from the pollen of Manuka trees. It is reported to contain an active ingredient MTG (methylglyoxal), which apparently has approved beneficial effects when its highly purified form is used as an adjuvant in skin wound healing[1]. Putting it in your porridge is no good! In fact, the available governmental data is that for every kilo of honey produced from the New Zealand Manuka tree, an amazing 7 kilos is sold worldwide. So when you buy Manuka honey (usually 6-9 times the price of regular honey) there is a 6 in 7 chance you are being conned (a probability of 86%). But of course if you really want to challenge your beliefs in the gurus, can I recommend you read my Hunza blog (July 22nd, 2014) and if you still believe in the wonders of Hunza water[2] you can get a great deal on Amazon[3]: ”Crystal Energy "Hunza Water" Buy 2, Get 1 Free!” Only $87.50 a pair!!

Turning to Traditional Chinese Medicine (TCM), the humorous side evaporates in light of the very disturbing findings on TCM by a consortium of Australian researchers[4]. They examined 26 TCMs using state of the art analytical equipment and their results can be considered in three areas

1.     The GENOMIC analysis: Sophisticated DNA analysis showed that many samples contained traces of animal species such as dog, cat (including Snow Leopard, an endangered species), frog, rodent, viper, and cow. In addition, many banned plant species were detected: Asarum or wild ginger is a source of Aristolochic Acid, a potent carcinogen; Ephedra, notorious for its use in slimming products where it is purported to act through increased cardiac output; Apocynum or Dogbane/Indian hemp which is poisonous with severe effects on the cardiac system.
2.     The DRUG analysis: Many drugs were detected which have no origins in TCM. These include the antibiotic amoxicillin; the anti-clotting agent, warfarin; ephedrine used to treat asthma and hay fever and drugs used to treat anxiety in veterinary practices.
3.     The CHEMICAL analysis: Arsenic, lead and cadmium at levels well in excess of food grade permitted maxima were widely detected. Multiple drug adulterants were also detected. One TCM had 10 times the permitted maximum levels of the poisonous compound arsenic.
Conclusion: Anyone who thinks that the word “traditional” or the accepted centuries old therapeutic use of a product in the absence of proof of purpose constitutes a vote in safety is quite simply naïve. It is precisely because modern food and medicines are so tightly regulated that they are totally safe to use and where necessary, proven to FDA standards to be effective. This paper raises very serious concerns not just about safety but about fraud. The idea that Snow Leopard was detectable in some samples is ecologically horrific. This beautiful species is the IUCN Red List of Threatened Species.