gibneyonfood

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

Monday, August 25, 2014

Obesity, depression, phobia and genes

The prevalence of clinical depression is about one third higher among obese versus non-obese subjects and there is conflicting evidence as to whether it is depression that brings on obesity or the reverse, where obesity brings on depression. To study this conundrum, a recent research project examined data from a longitudinal study of 18, 558 British individuals born in 1958[1]. This cohort was followed up at 7, 11, 16, 23, 33, 42, 45 and 50 years. Subjects were rated as underweight, normal weight over weight or obese. Those that were underweight had 1.3 to 2.3 times the risk of being depressed compared to those of normal weight. There was no evidence of a tendency toward depression among the overweight but among the obese, the risks of depression were between 1.5 and 2.3 times that of normal weight subjects. The data were then examined to see how either one of the conditions (obesity or depression), in prior years influenced the likelihood of the other condition subsequently developing. Being underweight predicted subsequent depression in both males and females (25% higher that those of normal weight) and depression predicted subsequent underweight in males only (84% higher risk). Obesity predicted subsequent depression in females only (34% higher risk). However, depression did not predict subsequent obesity. In all these calculations, confounding factors such as social class, physical illness and ethnicity were controlled for. The authors reflect on the fact that the treatment of obesity should also include an examination of possible depression but they ignore the elephant in the room, which is the stigmatization of the obese. By and large, the overweight and obese are seen by society, including health professionals, as having themselves to blame. They are seen as lazy, dishonest, untidy, lethargic, unreliable and so on. Sympathy with the overweight and obese is a rare occurrence.

A second paper[2] looking at a related topic, namely phobic anxiety, obesity and genes is also worth considering. Phobic anxieties relate to a wide range of fears that some people experience and the level of anxiety is measured on the Crown Crisp Index, which includes, for example, measures of claustrophobia fear of heights and crowds or hypochondriac traits. The subjects were participants in the Harvard based Nurses Health Study (5,911 females) or the Health Professional follow-up Study (3,697 males). They used genetic data on 34 genes linked to obesity. One was the FTO gene, which is the most widely studied such gene and another was the gene for a brain receptor involved in appetite regulation (MC4R). The remaining 32 genetic variants had been previously identified as increasing the risk of obesity in another study and were termed obesity risk genes. One of these 32 genes was also the FTO gene and these 32 genes had an additive effect on the risk of obesity. Average phobic anxiety scores were more 43% higher in women, which agrees with the general literature. The relationship between genetic factors and BMI was strong for the FTO gene, the MC4R gene and the 32 obesity risk genes. Higher BMI values increased the risk of phobic anxiety only among those carrying the common FTO genetic variant. After adjusting to an average BMI value, the FTO gene variant still had a direct association with phobic anxiety. Taken together, these data show that there is a common genetic link between obesity and phobic anxiety. The authors ask that their findings should be treated with caution and their hypothesis should be studied in larger samples. The finding that the collection of genes that had a linear rise in the risk of obesity did not link with anxiety suggests that obesity per se is not a cause of phobic anxiety and that the two conditions, obesity and phobic anxiety simply share a common genetic pathway

All in all, these two papers highlight the need for the study of the psychological conditions associated with obesity and they further highlight the need to study the reverse: how do psychological conditions contribute to energy imbalance

[1] Geoffrey, M and Power C (2014) Psychological Medicine, 44, 2461-2652

[2] Walter S et al (2014) Psychological Medicine, e publication ahead of print: PMID: 25065638

Thursday, August 21, 2014

The Human Microbiome ~ Myth and mystery

In the 1990’s, antioxidants were the big fashion in food and health. These antioxidants were mainly vitamins (C and E), pre-vitamins (beta-carotene) and plant constituents of various kinds (e.g. coumarin, flavonoids, thymol). Studies showed that rates of cancers across many countries were directly correlated with plasma levels of antioxidants. Laboratory studies showed that the damaging effect of pro-oxidant metals such as copper could be reduced with the addition of antioxidants. Every disease imaginable was included in the antioxidant Klondike. And of course we had the race to the finish culminating in a trial of Chinese smokers (smoking is pro-oxidant) with antioxidant supplements which showed the opposite to what was hoped for - cancer rates were increased! Many other trials were conducted but to date, little evidence exists to support the theory that taking antioxidant supplements reduces any disease risk. Of course that doesn’t bother the health food industry and to some extent the food industry from hyping up the antioxidant myth. This blogger learned one lesson from the antioxidant saga namely that any nutritional theory that is putatively related to many diseases, is a theory about to be shelved.

In today’s world of food and health, that role is played by the human gut microbiota. The front covers of The Economist, the New York Times magazine, Nature, Scientific American and others have highlighted articles with titles such as “Microbes maketh man” or “Our other genome”. There are wow statistics that journalists love: 100 trillion bacteria in our gut accounting for 1.5 kg of our bodyweight with 100 times more genes than we have (“We” are referred to as “Hosts”!). To journalists, it is an astonishing mystery that bacteria, previously thought to be bad for health were in fact our single most important protection against an array of diseases. A search of the PubMed database shows the term “Gut microbiome” is associated with the following diseases (number of published papers in brackets): obesity (628), cancer (381), diabetes (350), allergy (260), depression (48) and autism (33). I stopped there but I’m sure I could go further. The point is that the gut microbiota is the new unifying theory of life and death.

A very welcome paper in this week’s Nature bears the title “Microbiome science needs a healthy dose of sceptism”[1]. The author’s first point of criticism is that the techniques used to characterise the microbiota genome often lack direct links to known functions. He points out that his team has shown that vaccination eliminated 30% of known pneumococcal strains in a human population but only because they knew which genes to focus on. In the case of the human microbiota genome, we might know that it differs between say normal weight and obese subjects. But that’s all we know. We cannot tell what part of the microbiota genome is directly linked in a causal manner to obesity. His second criticism is linked to this in that cause and effect are misinterpreted when looking at gut microbiota. He cites a paper, which shows that changes in the human microbiota correlate with measures of frailty in older persons. So too did dietary patterns. The conclusion was that poor diet altered the gut microbiota and thus led to frailty. The opposite was not considered, namely, that frailty led to poor diets that in turn altered gut microbiome patterns. His third criticism is that most of the studies lack any mechanistic explanation based on experimental investigation. In that respect the field is similar to nutritional epidemiology where correlations dominate and shape policy in the absence of any experimental proof. So if we consider the microbiome-diet-frailty issue, a simple test would be to take a cohort of frail persons and through physiotherapy, counseling and nutritional support reduce their frailty. If a significant improvement in frailty had no effect on the microbiome, we can dismiss that theory. Alternatively, frail persons could receive faecal transplants to modify their microbiota and examine the effect of improved microbiota on frailty. His fourth criticism relates to the quality of the data on the microbiota and health vis-à-vis the real world. He highlights the fact that many of the studies that show the importance of the gut microbiota are conducted in germ-free mice. Such mice live in an aseptic bubble that makes them generally ill and with poor food intake. Finally he asks if there might be a confounding factor such that the real force driving the disease is one thing and the altered microbiota simply an observer, equally effected by the true driver.

In his paper, Professor Hanage who works in Harvard, cites a blog by Professor Jonathan Eisen of the University of California at Davis in which he makes an award for “Overselling the microbiome”[2]. He shows how research results are manipulated by university press offices and swallowed easily by journalists. Two collaborating Swedish university research groups published a paper in Nature Communications[3] and they wrote thus:

“Our finding of enriched levels of phytoene dehydrogenase in the metagenomes of healthy controls and its association with elevated levels of β-carotene in the serum may indicate that the possible production of this anti-oxidant by the gut microbiota may have a positive health benefit”.

In the press release[4] we read the following:

“Our results indicate that long-term exposure to carotenoids, through production by the bacteria in the digestive system, has important health benefits. These results should make it possible to develop new probiotics. We think that the bacterial species in the probiotics would establish themselves as a permanent culture in the gut and have a long-term effect”. “By examining the patient's bacterial microbiota, we should also be able to develop risk prognoses for cardiovascular disease", says Fredrik Bäckhed, Professor of Molecular Medicine at Gothenburg University. "It should be possible to provide completely new disease-prevention options".

The present fashion of the microbiota has a powerful scientific dimension but it is over-hyped and under-studied at the human experimental level. Whist many good human experiments are done to study the human microbiota, most are poorly constructed, observational and in rodents, normal or germ free.