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Tuesday, July 14, 2015

Peanut allergy - a new breakthrough

Between 1997 and 2010, the incidence of peanut allergy quadrupled in the US In 2000, the American Academy of Pediatrics recommended that for children who were inclined toward allergic diseases, peanuts should be avoided until 3 years of age. Moreover, recommendations were made to pregnant and lactating mothers to avoid peanut consumption. Everywhere, from schools to jet aircraft, from restaurants to kiddies’ parties, the terror of peanuts prevailed. A group of UK allergists noted that among Jewish children in London, the risk of developing peanut allergy was 10 times that of Jewish children living in Israel. This was associated with a difference in the age when peanuts were introduced. Among the London Jewish kids, peanuts were generally not introduced until the second year of Life. Among Israeli based Jewish children, it was on average 7 months when peanuts were introduced. Several small and generally inconclusive studies had suggested that in fact early introduction of allergens such a cows’ milk or eggs, tended to reduce the severity of the disease. Thus the UK researchers set out to design a large randomised trial of the early versus late introduction of peanuts to children. The trial was called the LEAP trial: (Learning Early About Peanut Allergy[1])

To enter the study, the infant had to be aged between 4 months and 11 months and to suffer either severe eczema or severe egg allergy. The children then underwent a skin prick test for peanut allergy. Of the 834 infants who were screened for the study (194 did not meet the exact inclusion criteria), 640 underwent randomization. Of these 542 had shown a negative skin prick test to peanut allergy while 98 did show a positive test.  Half of these groups were then allocated to either complete peanut avoidance or controlled peanut consumption. Controlled peanut consumption involved a weekly intake of at least 6 grams of peanut protein from an Israeli peanut snack “Bamba”. The consumption and avoidance of peanuts would continue for 60 months. The prevalence of peanut allergy at 60 months was the chosen end point. In randomised controlled trials, there are two ways to analyse the data. One in called “intention to treat” and this includes all subjects irrespective of how they adhered to the protocol. The second is the “per protocol analysis” which includes only those children that adhered to the study protocol as set out at the beginning. Taking the former approach first, at 60 months, on average 17% had peanut allergy and 3% didn’t. When one looked the those who had a positive skin prick test, a staggering 35% of those who avoided peanuts went on to be peanut allergic while among those exposed to peanuts, the level was just 11%. This was thus a 3-fold higher risk. Now taking the per-protocol analysis and focusing on those who were skin prick positive to peanuts at the outset, 34% of the avoidance group went on to be peanut allergic (in effect the same as the intention-to-treat analysis). But among the children who had a positive skin prick test to peanuts at the outset, and who consumed peanuts, not a single case of peanut allergy was seen at 60 months.
This trial will have profound effects on how we treat infant and childhood food allergy. Avoidance is obviously not the key. Controlled introduction and controlled feeding is the key but more needs to be done to figure out how this best operates for different foods and for infants with different allergy experience. However, one thing is sure. The old default of avoidance is out the window

[1] Du Toit et al (2015). Randomization trial of peanut consumption in infants at risk for peanut allergy. N Eng J Med 372, 803-813

Tuesday, June 9, 2015

Real nutritional science re-affirms advice to lower dietary saturates

In the last few years there has been a flurry of scientific papers published showing no apparent association between deaths from cardiovascular disease and the consumption of dairy products leading to an amazing level of interest in the traditional and the social media in these new revolutionary findings. “Butter is back”, wrote the New York Times while Time Magazine featured a cover story headlining “Eat butter – the scientists labeled fat the enemy. Why they were wrong”. The Wall Street Journal ran a feature entitled “The questionable link between saturated fatty acids and heart disease. The meat, dairy and egg industries had a field day. However, little ol’ me pointed out in a blog entitled “Fats, facts and baloney[1]”, that these scientific assertions were based on a re-analysis of all existing data that examined the association between consumption of dairy foods, saturated fats and heart disease rates. Let me stress the word “association”. Epidemiological studies examine some aspect of lifestyle such as diet and some putative link to that lifestyle and seek to explore whether the link is positive, negative or otherwise on the basis of statistical analyses. No matter what statistically significant effect is seen and no matter how often it is repeated across time and space, it remains an association. A causal effect of the lifestyle factor and the putative end point of that lifestyle has not been proven. In certain areas of epidemiology, it is impossible to follow this association up with a human intervention study to prove the cause-effect association. Thus when epidemiologists studied the link between cancer and tobacco, experiments in humans were out of the question. To that end, a famous English epidemiologist, Sir Austin Bradford-Hill set out a list of criteria that should be considered in perusing epidemiological data to ensure that any conclusion drawn on such data, are, as far as is humanly possible, plausible and actionable. I have never seen or read of any nutritional epidemiologist citing the Bradford Hill criteria.

Now what makes nutritional issues different from the tobacco issue is that we can and do large human intervention studies in which one group has their food intake or nutrient intake manipulated, while another serves as a control. Examples include studies of diet and cancer and cardiovascular disease in women[2], studies of the Mediterranean diet[3] or studies of dietary lipids and the metabolic syndrome[4] to mention just a few.

In recent months, two papers have appeared from UK researchers, in which the level of dietary fat and the type of dietary fat were manipulated[5], [6]. The first in volved195 subjects aged 21 to 60 years with moderate risk of cardiovascular disease. They were randomly allocated to one of three intervention diets for 16 weeks in which the ratio of saturated to monounsaturated to polyunsaturated fats varied: 17, 11, 4 versus 9, 19, 4 versus 9, 13, 10 to provide diets high in saturates, monounsaturates or polyunsaturates. Replacing saturates with monounsaturates or polyunsaturates resulted in statistically significant falls in plasma cholesterol both total and LDL cholesterol (about 9% and 12% respectively). This was calculated to translate into a reduction on cardiovascular disease mortality by up to 20%. The second study involved 165 healthy adults assigned to a standard British diet or to a diet that attempted to meet the UK dietary guidelines.  The group assigned to the dietary guidelines arm of the treatment showed a reduction in the intakes of total, saturated and trans fat intakes with a partial substitution with increased intakes of polyunsaturates but especially, monounsaturated fats. Total and LDL cholesterol fell significantly over the 12 weeks in the group assigned to the dietary guidelines. The estimated overall reduction in heart disease mortality was between 15 and 30%.

Now it matters nothing as to how many epidemiologists dance on a decimal point, the facts remain that adhering to existing dietary guidelines on the composition of dietary fat, which have changed rather little in the last 50 years, will significantly reduce heart disease death rates. These data are experimental proofs of what was already proven many times many years ago. However, in an era where epidemiology and its statistical gymnastics rule, it was necessary once again, to show that the adherence to prevailing dietary guidelines is justified and will save lives. These papers won’t hit the Wall Street Journal, Time Magazine or the New York Times. The general public will never hear about them. I happen to care, hence another rant!

[3] Estruch R et al (2013) N Eng J Med, 368, 1279-1290
[5] Vafeiadou K et al (2015) Am J Clin Nutr, e pub ahead of print
[6] Reidlinger DP et al (2015) Am J Clin Nutr, 101, 922-930

Thursday, May 28, 2015

Obesity, poverty and convenient myths

Policy makers don’t read tabloid newspapers. They read more serious broadsheets from the London Times to Figaro to the Washington Post. And these broadsheets often perpetuate the beliefs that make the upper social echelons happy or indeed smug. And among these beliefs is that which argues that the present epidemic in obesity is primarily a problem of the lower socio-economic groups. One cannot argue against the line that obesity rates are higher among the socially disadvantaged. Neither can one argue against comparably higher rates of suicide, homicide, drug abuse, violent crimes, indebtedness, heart disease, cancer and anything you care to mention but which you’d rather do without, thank you very much.

The fact that obesity, like suicide and homicide, is higher in those who are socially disadvantaged doesn’t mean it is absent in the socially advantaged. The differences in obesity rates are in high fractions such as 0.8 or thereabouts such that for every 5 obese persons who are socially disadvantaged, there are 4 obese persons among the economic elite. Think of the Clintons, Hilary in recent times and Bill, a while back. However, as I’ve already said, obesity is higher among the socially deprived. The question is why so and what to do about it.

A recent paper in the American Journal of Public Health[1] looked at residence mobility in relation to social status and the economic deprivation of the areas of residency in the city of Dallas. The study was part of an on-going study on heart disease and followed subjects (about 1,800) over the period 2000 to 2009. Weight was monitored at baseline, at various intervals and at follow up. Half the subjects moved from one neighbourhood to another and of these, 600 subjects moved to a neighbourhood with a higher ‘Neighbourhood Disadvantage Index’ (NDI: ~ perceived neighbourhood violence, poor physical environment, and low social cohesion). Compared to those who moved to a neighbourhood with a lower NDI or who remained where they originally resided, those moving to a higher ranked NDI suburb gained significantly more weight and the longer the residence in the higher NDI suburb, the greater the weight gain.

Well of course, the answer is simple. These people moved to “food deserts”, the trendy middle class quasi left wing term to describe regions which are so poor, its not worth anyone’s time and money in building them a supermarket. Consequently, the creed goes, they cannot get access to affordable and varied food supplies but are forced to shop in local stores that don’t sell fruit and vegetables at a reasonable price and which prefer to stock their shelves with cheap and, of course, high fat, high sugar and high salt foods (Credo in unum dieta!). Enter a governmental initiative that subsidised the building of a brand new supermarket in the suburb of Morrisania in the New York borough of the Bronx with a ‘control’ suburb of Highbridge where no such investment was made. A research paper just published[2] examined food choice 5 weeks and 52 weeks after the supermarket was opened. The authors concluded as follows: “The introduction of a government-subsidized supermarket into an underserved neighbourhood in the Bronx did not result in significant changes in household food availability or childrens dietary intake. Given the lack of healthful food options in underserved neighbourhoods and need for programmes that promote access, further research is needed to determine whether healthy food retail expansion, alone or with other strategies, can improve food choices of children and their families”. So, access to healthy food options is not the issue. It is most likely lifestyle choice arising from a particular educational stance.

Now enter the ultimate holy grail of the urban middle class food priests, the Farmers Market. What can be more morally upright than buying wholesome food directly from the farmer who toiled the land to produce such heavenly fare? Well, a recent study[3], also in the Bronx, paints a different picture. Following a comprehensive study of farmers markets (FMs) in this region, they conclude as follows:  (1) FMs operate overwhelming fewer months, days, and hours than nearby stores, (2) FMs carry less-varied, less-common, more-expensive produce than nearby stores. (3) FMs offer many items not optimal for good health (e.g., jams, pies, juice drinks) and OMG, (4) FMs might provide little net benefit to food environments in urban communities.

Social inequality lies at the heart of many patterns of chronic disease. Tackling it is outside my expertise but I’ll vote for it

[1] Tiffany M. Powell-Wiley et al (2015) Am J Public Health, in press
[2] Ebel B et al (2015) Public Health Nutrition, Feb 26:1-10.

[3] Lucan SC et al (201)  Appetite 90, 1 July 2015, Pages 2330

Sunday, April 19, 2015

Personalised Nutrition: A look into the future

Personalised nutrition is the future. When the sequence of the human genome was first announced, it was believed that human biology had set a new boundary around its research challenges. It was believed to herald a new dawn in cancer prevention when President Bill Clinton and Prime Minister Tony Blair launched the human genome sequence project in June 2000. Clinton commented: “In fact it is now conceivable that our children’s children will know the term ‘cancer’ only as a constellation of stars” to which Blair added the this heralded: “a breakthrough that opens the way for massive advances in the treatment of cancer”. The era of personalised medicine had arrived and the road ahead was envisaged thus: You doctor would have your genome scanned to check some conditions such as blood pressure where your measurements were marginally high. She or he might find you had a genetic predisposition too high blood pressure and based on your genetic information, the ideal pharmaceutical treatment to stave off hypertension would be identified. Armed with a prescription from your doctor you would go to your high street pharmacist and buy the prescribed drugs and maybe what today is called a ‘companion diagnostic’, a home blood pressure monitoring machine.

The temptation to translate this model to human nutrition was very attractive and so genetic testing companies were set up where for about  €200 a pop, you could be screened for genetic variants associated with diet related diseases. The industry flopped for two reasons. Firstly, when someone is told to eat more fish oil because they have some genetic variant indicative of declining cognitive function in which fish oil fatty acids might play a protective role, it has to be borne in mind that those same fish oil fats influence blood clotting, blood lipids, inflammation, vision and so on. So how could they be sure that what was good for treating cognitive function was maybe bad for your vision or inflammation? Drugs have one single point of action. Nutrients have multiple points of action. The second is that it’s not good enough to tell Homer Simpson he has a genetic variant which influences his cardiac electrophysiology and thus he needs to “watch” his lipids and salt. No, Homer wants a solution, not a problem. There is no wonder drug and no pharmacist to help him. He has to go to the supermarket and start making choices as to the foods that will help balance his lipids and salt. So, he needs customised solutions.

Enter Food4Me, a €9m EU funded project, which looked at all aspects of personalised nutrition: Consumer attitudes, business opportunities, legal and ethical issues, new emerging technologies which give biofeedback and most importantly, an internet based proof-of-principle study of the value of fully internet delivered personalised nutrition which involved providing genetic information, blood analysis and a personalised dietary analysis with feedback and coaching. The latter was the biggest hit with the 1,300 subjects who too part in the 7-centre pan EU study. Subjects entered their data on habitual food intake following a simple template across the Internet. That food intake data was translated into actual weekly nutrient intake and these data were compared to established international standards. The feedback was graphic. If the little cartoon man was in red for calcium you had a major problem to tackle, if it was in amber, it was in need of addressing soon and if in green, it was ok. The subject then was told why they had the problem they had with each nutrient based on their habitual food choice. A high intake of cheese might put calcium in green but saturates in red. A high intake of soup might put energy in green but salt in red. So for the three most urgent nutrients, they received detailed coaching on how to change their food choice to optimise their diet. Unlike Homer walking into the supermarket knowing his problem but not his solution, our subjects went to the supermarket knowing exactly, for them, what foods to chose to optimise their diet. Did it work? Yes it did when compared to a control group who were not given personalised dietary analysis but generalised population healthy eating guidelines.

So the future is thus. Whether by smart phone or a home computer, food choice is inputted and nutrient intake calculated by the service provider who then tells the used the top three problems to solve and what food choices to make to improve things. In fact, the advice won’t be at food level but at a weekly menu level taking into account data on personal taste, access to food, allergies and intolerances and price. This data will be shared with three other players: your smart fridge, a range of supermarkets and your work canteen. The supermarkets will translate the weekly menu into a shopping list and give you a price whereupon you will make your choice and the groceries will be delivered to your door. The smart fridge knows what’s ay home and expects you to interact with the touch screen on the door to indicate what you’ve taken out. I log on: “Good morning Mick” it says and I press a button marked ‘the usual so it deducts a bowl of porridge with milk and sugar, a glass of orange juice and tea. The information is shared with my computer, which now builds up my weekly aggregation of nutrients. Now it re-adjusts its record of the food store. In work I pick a soup and roll and using my swipe card at the check out, and both my computer and smart fridge are informed. On Thursday, I choose fish and chips at work and I swipe my card and I now get a text telling me that I have now reached my 90% limit of salt intake and I have a shortfall in fibre intake. When I get home, my smart fridge that now knows this problem and knows what’s in the kitchen offers several menus to boost my fibre with low salt meal recipes. I pick one but don’t know how to cook it so the smart fridge scans You Tube for demo and away I go.  It’s the future. The white goods industry, the IT industry, retailers, caterers and the food sector are hatching it.

In this analysis I have left out genetic based information, which is a long way off and the postal based blood biochemistry, which is presently operational. If you’d like to read about the project click here and if you’re a little lazy, then watch a 15-minute video on the findings here.