Wednesday, May 30, 2012

Why a fat brain made us more vulnerable to heart disease

Natural selection granted us large brains. The evolutionary cost is having to feed them. The human brain's high-energy demands led to development of a strong preference for fat. We consume more fat than any other primate on average. We are also adapted to more easily digest and metabolize fats.

There are two major kinds of fat that our brains depend on most for its development and regular maintenance. These are the long-chain polyunsaturated fatty acids (LC-PUFAs), omega-3 docosahexaenoic acid (DHA) and omega-6 arachidonic (AA). These two LC-PUFAs can't be made de novo, making them essential in the diet. DHA and AA are supplied by seafood, eggs, or animals. They can also be supplied as their 18-carbon precursors alpha-linolenic acid (ALA) and linoleic acid (LA), found mainly in plants and their seeds.

ALA and LA precursors require conversion to become long-chained through a series of steps of desaturation and elongation. In particular, delta-5 and delta-6 fatty acid desaturases build onto the carboxyl end of the carbon chains of the ALA and LA by introducing double bonds. These converting enzymes are rate-limiting.

The rate-limiting enzymes are encoded into the genome by FADS1 and FADS2. The FADS region has been of special interest to researchers because of variations in single-nucleotide polymorphisms (SNPs) that could lend clues about human evolution including our larger brains. Yet, to date, there have not existed any studies evaluating FADS mutations among humans and related species.

Now, researchers from Uppsala University, in Sweden, along with scientists at MIT, Harvard, and major European Universities, have found genetic variation in the FADS region in present-day humans that made them uniquely adapted to biosynthesize DHA and AA. The same adaptations could also help explain why some ethnicities have a higher susceptibility to chronic disease today.

The international team set out to investigate by using genomic data from contemporary human populations, archaic hominins, and more distant primates. They used SNP genotype data from more than 5,600 individuals across five European population cohorts. They evaluated mutations in the FADS region that are strongly associated with omega-3 and omega-6 fats.

Two common FADS haplotypes

Among present-day humans, they report, exist two common FADS haplotypes, or groups of alleles defined across a set of 28 SNPs, that are "dramatically different in their efficiency" to biosynthesize DHA and AA from he shorter ALA and LA.
The 28 SNPs of two main haplotypes (A in red, D in blue) and nucleotides of species.

Haplotype A, limited in conversion efficiency, appeared nearly 606 thousand years ago. Rhesus monkeys, chimpanzees, gorillas, and Denisovans all bear haplotypes "very similar" to haplotype A. Neandertals too, although based on incomplete sequences, have similar haplotypes to haplotype A.

Haplotype D, having greater conversion efficiency, appeared somewhere between the lineage split with Neandertals. That was around 500 thousand years ago and before the exodus from Africa some 50 to 100 thousand years ago. Both haplotypes must've been present during the exodus or else we wouldn't see the existence of them in modern humans today.

The researchers speculate that "a very rapid increase in brain size of hominoids" probably involved selection and the increased frequency of haplotype D. That does not mean that haplotype D had any direct effect on brain size, but that it was highly advantageous in environments where there was limited access to AA and DHA to feed the brain.

Haplotypes A and D in Present-day Humans

Nowadays, the researchers found, nearly all individuals of African descent had haplotype D. The high frequency indicates positive selection for the haplotype with more efficient conversion in the face of limited availability of LC-PUFAs in early Africa.

On the other hand, nearly all Native Americans had haplotype A. The reason, the researchers propose, may be because of a "bottleneck effect in the colonization of the American continent, possibly in combination with relaxation of the selective pressure as a result of a diet higher in essential LC-PUFAs."

The data are mixed in those descended from Europe, Oceania, East Asia, who are reported to have haplotype D at a greater frequency.

The frequencies of A (blue), D (red), and mixed (gray) haplotypes.

Health Implications

How can the knowledge of these haplotypes inform guidance on diet? The differences in haplotypes may explain why individuals of specific ethnicities may be more susceptible to chronic disease compared to others.

Individuals with haplotype D biosynthesize more AA and DHA than individuals with haplotype A. While this adaptation may have been useful on the African savannah, the researchers propose it has drawbacks as a "thrifty genotype" in our modern world. As plentiful as LA (from corn and soy) is in the Western diet, haplotype D may lead to higher levels of AA-derived pro-inflammatory eicosanoids, which raise the risk of atherosclerosis and coronary artery disease.

A different set of problems are presented for individuals with haplotype A. These individuals may be protected against a high-LA diet to a degree because of limited conversion to AA. However, they are more dependent on animal foods for adequate amounts of DHA due to inability to convert sufficient ALA to the longer-chained counterpart on a more plant-based diet.

The researchers propose, "FADS genotyping should be included as a diagnostic for dietary recommendations."

As genetic testing is not yet widely available, here's a more viable solution for the sake of a large human brain and a genome not well adapted to a high-LA diet: eat less LA; and, eat more foods enriched in long-chained omega-3s such as eggs, grass-fed animals, and seafood.


Ameur et. al. Genetic Adaptation of Fatty-Acid Metabolism: A Human-Specific Haplotype Increasing the Biosynthesis of Long-Chain Omega-3 and Omega-6 Fatty Acids. American Journal of Human Genetics, April 12, 2012 DOI: 10.1016/j.ajhg.2012.03.014

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Monday, May 28, 2012

AMOUR, My Last Car, thoughts on Neuroscience, RNCM Concerts at Manchester Hospitals and New Opportunities...

Over the last few months, meeting Richard Creme and being part of that group of people who worked with him to get his exhibition together, was such an eye opener - such a rich treat. It’s got me thinking though. Stroke, like any health crisis or disease that affects our brain, has such a profound impact on who we are and how we’re perceived. I constantly meet people who want to talk about their practice and evidencing the impact of their work on people who may be experiencing dementia, or may have had a stroke.  It’s always interesting and really varied: musicians, film-makers, poets and painters. More often than not, people will bring up the idea of recruiting a neuroscientist as part of the research team - someone to sit alongside the health economist, to take their hypothesis further: provide the empirical evidence of arts intrinsic value.

Like everyone, I’m seduced by the shimmering possibilities of medicines new frontier, of a pulsing supernova at the heart of our being - the dancing, golden synapse - the phrenological centres of our individuality. Compartments for love, pleasure, remorse and so much more...

So it was with great interest, that I read  an article by Vaughan Bell who’s a visiting senior research fellow at the Institute of Psychiatry at Kings College London, and who suggests that the data that scientists pull from fMRI brain scans, isn’t always reliable, and as I’ve discussed before, like the Randomised Controlled Trials (RCT) - are subject to cultural issues including the incentives offered by the  industry. Just think of the unreported negative findings in pharmaceutical trials; Seroxat and Reboxetine being just two. Bell’s article which focuses on brain scans specifically, does make me feel that whilst the range of scanners that exist as diagnostic tools are reaping significant results, the exploration of what it is to be human, is ever-so-slightly more complicated. His article, which illustrates the increasing use of neuro-imaging in deciding the guilt of prisoners in India, Italy and the US, opens up an interesting and worrying debate.

Over the last decade i’ve seen increasing calls to legitimize the arts in relation to health and well-being, particularly calls to standardise what it is we do, so that the NHS can embrace our agenda. Increasingly this is an aspiration to gain NICE approval, through RCT’s, or perhaps sometimes spurious evidence that art lights up the brain. I’d suggest that whilst there is space for intelligent collaborations between artists and scientists, in focusing solely on evidencing arts value, we’re missing the point - isn’t our work about exploring that liminal space between the arts, science and what it is to be human? Standardised repeat prescriptions for the arts, and reductive understanding of its value, risk reducing us down to a simmering stew of amino acids...

MY LAST CAR Looking Well, Bentham                  30th May - 2nd June

Do you remember your first car? How about your last?

My Last Car is an epic road trip that explores the life and death of the car through a series of poignant, funny and uplifting tales.  Our voyage is part exhibition, part live performance and part community celebration. It explores all that the car means to us at the end of a great transport era. We have carefully dismantled a Rover 316 Cabriolet and filled a gallery with thousands of car objects. From wipers and cogs, windows and springs to camshafts, pistons and filters. Each part is labeled with messages and stories, facts and dreams about cars. The car becomes becomes the stage set for our performances. We tell tales of cars both good and bad. We look at the future and what it might hold. We share moments of magic, mystery and and motorway madness.

There is so much to do! Celebrate My Last CARnival: a festival of events and activities on the streets of Bentham, attend My Last Car Live Performances, and visit My Last Car – The Exhibition. My Last CARnival is a lighthearted celebration of life in a town with and without cars. It tips its hat to the trusty motor car and celebrates other ways of moving around. Get out of your car and discover a Boom Bike and a bus-shaped bus shelter or journey through space and time for a pound. Walk or bike the CARnival trails, meet ‘The Queen’ and happen across film, sculpture and performances in unexpected places!

Bentham Town Hall has been chosen as one of only two places in North Yorkshire to host My Last Car, the original performance and exhibition by 509 Arts as part of imove – Yorkshire’s Cultural Olympiad programme. Inspired by read stories of break ups and break downs, crashes and jams, it celebrates and questions our relationship with the car over years and across generations. Bentham will be the canvas for installations created in unexpected venues within walking distance the My Last Car event. My Last CARnival is a lighthearted celebration of life in a town with and without cars. It tips its hat to the trust motor car and celebrates other ways of moving around.
If you visit the My Last Car website, you can upload your own car story! Here's a snippet from mine.

'Once upon a time, I held down two jobs - one in Cornwall, the other in Manchester. It was ridiculous. One week here, the other week there. I chose to drive between the two at night to avoid the traffic jams and snarl-ups. I slept in the afternoon, drove through the night. A pattern, a habit. Full moon over the M6, sunrise over Bodmin: perfect.
One night, (at Junction 17 to be precise) driving the same old routine - my yellow headlamp beam changed, something strange darted in front of the car - the most exquisite  hare. Not some regular rabbit, but a beautiful, (and in my memory) giant hare - elegant and so, so long. But so beautiful in the tungsten glare, that I swerved to avoid it - swerved to avoid metal on flesh...'

EXTERNAL EVALUATOR for KiiCS project: apply by 20 June 2012
Knowledge Incubation in Innovation and Creation for Science is a three-year European Commission-funded project (2012-2014) coordinated by Ecsite, the European network of science centres and museums. It aims build bridges between arts, science and technology by giving evidence of the positive impacts of their interaction for creativity as well as for triggering interest in science. The project will stimulate co-creation processes involving creators and scientists, and nurture youth interest in science in a creative way.
KiiCS offers a financial contribution of a maximum of 30.000€ and if you are interested, you should submit the tender before June 20, 2012. The proposal must be delivered in English and it has to include a brief description of the methodology to be used and analytical framework, a work plan with detailed Schedule and the distribution of budget for the evaluation.
For more information about this position, contact KiiCS:


OK, so I’ve not seen this film and its just been awarded the Palme d’Or at the Cannes Film Festival, but it looks relevant to our Arts/Health in that it deals with aging, music and stoke in one fell-swoop.  Michael Haneke has made some interesting films in the past and this looks like something very beautiful indeed, dealing with emotions but without cloying sentimentalism. You can find more by clicking on the link below and here’s the official trailer with English subtitles.

‘Jean-Louis Trintignant and Emmanuelle Riva give breathtaking performances as Georges and Anne, retired music teachers in their 80s, living in a handsomely furnished, book-lined Paris apartment with a baby grand piano. They are happy, affectionate, loving; active and content. We see them attending the performance by one of Anne's former pupils, and are delighted with his success. But one day, Anne suffers the first of a series of strokes which paralyse one arm, making playing the piano impossible, accompanied by progressive dementia...’
‘...using your own words and methodologies, calling into question both the vocabulary and content of the research that was requested and making divergent, dissonant and improbable proposals.’

What an invitation!!

The international call is open for artists and social scientists to collaborate with the following seven organisations located in the Basque Country (Spain) as part of the 2012 edition of Improbable Connections: Artepan (artisanal bakery and pastry maker), EDE Fundazioa (social intervention), Eraikune (construction cluster in Euskadi), Grupo Uvesco (supermarkets), Oiz egin (rural development platform), Orbea (design and manufacture of bicycles) and Silam (Products and solutions based on silicone elastomer).
Deadline: 9am on 25 June 2012. 
Collaboration period: September 2012 - June 2013. 
Payment: 12,000 euros + VAT (including travel and accommodation).

Thank you as ever...C.P

Sunday, May 27, 2012

Good insulin, bad insulin: Its role in obesity?

Gary Taubes makes insulin out to be a bad guy. In his latest article in Newsweek Magazine commenting on HBO's Weight of the Nation documentary, he once again challenges energy balance (energy intake versus energy expended) as a paradigm for understanding obesity. The author of Good Calories, Bad Calories offers an alternative theory: refined sugars and grains trigger insulin, which leads to fat accumulation. He also doesn't think much of physical activity as playing a "meaningful role in keeping off the pounds."

Is Taubes right? Not according to Jim Hill, Ph.D., a professor of pediatrics and medicine at the University of Colorado School of Medicine, Denver. Hill is the cofounder of the National Weight Control Registry, a registry of individuals who've succeeded in maintaining weight loss over time. He is also the co-founder of America on the Move, a national weight-gain prevention initiative.

At a session at Experimental Biology, Hill said that the the "energy-in energy-out" framework continues to dominate as correct in current scientific literature on obesity. When asked whether or not the rise of obesity epidemic is related to diet or physical activity, Hill simply responds, "Yes." That is because studies have shown that either restriction of calories or greater physical activity can lead to weight loss.

Then, what's wrong with Taubes's insulin hypothesis? First, it's important to point out that insulin is also a good guy. As kinesiologist John Ivy, Ph.D., of the University of Texas at Austin, pointed out to me a few years ago, insulin is too often misunderstood. The unfortunate consequence can be a detriment of muscle and strength. Ivy's own research is on muscle insulin resistance and how it is reduced with exercise.

Insulin's role is more clearly explained in Ivy's book The Future of Sports Nutrition: Nutrient Timing. He writes that, yes, insulin is a promoter of fat synthesis. But it is also a crucial hormone for promoting protein synthesis, reducing protein degradation (including suppressing cortisol, which can be catabolic in nature), and promoting glucose uptake and glycogen storage in muscle. Insulin, notably, also suppresses appetite.

According to Ivy, the most important factor involved in whether or not insulin promotes fat storage, carbohydrate storage, or protein synthesis is the "individual's body state." For example, under conditions where insulin sensitivity heightened in fat cells (a sedentary lifestyle), there will be more promotion of fat storage. On the other hand, after physical activity, when muscle cells are more insulin sensitive, insulin will promote glycogen and protein synthesis.

Perhaps where Taubes goes wrong is in failing to realize the role of muscle in body metabolism. It wouldn't be the first time. As I've discussed before in a post about the work of another kinesiologist, Stuart Phillips, Ph.D., of McMaster University, skeletal muscle is often forgotten in discussions of obesity. However, as Phillips affirms, skeletal muscle is a highly metabolically active tissue, consuming a great deal of energy as a primary site for glycogen storage and the largest site for fat burning. Skeletal muscle mass also helps determine metabolic rate.

Taubes, in this latest article, also fails to mention that carbohydrate is not the only macronutrient that stimulates insulin. Protein stimulates insulin too; in fact, it's the branched-chain amino acids (leucine, isoleucine, valine) that trigger the insulin release -- these same amino acids are also the key players in triggering protein synthesis, which is explained in part by their effects on insulin.

Ivy explains that insulin has earned the title "anabolic regulator of muscle," meaning it's the most important hormone to increase muscle and strength. Yet, by Taubes's judgment, insulin release should be avoided as much as possible. Taken to its logical conclusion, Taubes's mindset means that one should eat less carbohydrate and protein per day, and eat plenty more fat -- along with the dismissal of exercise as being important, that's the perfect recipe for gradual muscle degradation and (what?) insulin resistance, hyperglycemia, and hyperinsulinemia!

Is there something really wrong with "eat less, move more"? After all, this "tired advice" as Taubes calls it has largely failed in producing results in the United States. There still exists an obesity epidemic and it's getting worse. Is there another alternative theory to energy balance? Hill says energy balance still stands, although he acknowledges "eat less, move more" is too simplistic as advice. He offers his own new paradigm, which largely represents what other nutrition scientists have concluded including the American Society for Nutrition (see my report here). It's that "diet and physical activity interact." And how they interact may explain how the body regulates -- with a sort of "settling point," according to Hill -- balance of energy, energy stores, glucose, and temperature.

Looking at the problem from historical standpoint, Hill reminds, we no longer have to hunt or travel long distances to gather food anymore. We no longer have to farm to produce our food. Now, it's all about heading to the supermarket, filling our carts, and sitting in some form or another for the rest of the day. Our environment has changed. What's the solution to an obesity epidemic? Hill suggests in taking "small steps" for changing our environment back; this means continuing with "eat less, move more," and finding any opportunity to bring reduced-calorie eating, walking, and other physical activities back into lifestyles.

Another recommendation comes from Ivy and Phillips, which is to make greater use of the "anabolic regulator of muscle" and focus on muscle maintenance and growth through regular physical activity. They also encourage balanced eating with healthy portions of quality protein, carbohydrates, and fats. Yes, carbohydrate is important for endurance and maximal recovery of glycogen stores.

Resistance training is primary for muscle building; aerobic exercise also helps in depletion of glycogen stores. Both forms of physical activity make muscles more insulin sensitive, cause greater uptake of glucose into muscles, and they also help keep extra calories from heading toward fat stores. Far from Taubes's advice that physical activity is meaningless, these kinesiologists suggest some form of exercise should happen every single day.

To greater understand the role of "nutrient timing" and how carbohydrate and protein relate to exercise, read Ivy's book and see this 2008 position statement from the International Society of Sports Nutrition where Ivy serves as part of the editorial board.

Update: Those of you who've read Good Calories, Bad Calories or Why We Get Fat may also be interested in Yoni Freedhoff's review of the latter over on his "Weighty Matters" blog. I have only read the first book.

Saturday, May 26, 2012

Fate of fructose: Interview with Dr. John Sievenpiper

Fructose metabolism. Ref: Tappy & Ka 2010.
Sugar is a hot topic these days. Evidently, it's also a touchy topic. I've been a little amazed at some of the responses (both positive and negative) received since my first rant post about media reporting unfairly that hummingbird fuel was "toxic". There clearly exists a continued need for education about the state of the evidence as it stands now surrounding sugar and its implications on health.

As a follow-up to my report of the "Sugar Showdown" at Experimental Biology -- a debate where scientists voiced clear dissatisfaction with the sensationalism surrounding sugar both in news reports and in the scientific literature -- I decided to seek out greater insight by an expert who was at the event.

John Sievenpiper, M.D., of St. Michael's Hospital, University of Toronto, brings a valuable perspective to our understanding of sugar. He is the lead author of three recent systematic reviews and meta-analyses evaluating fructose's effects on body weight, blood pressure, and glycemic control in humans from randomized controlled feeding trials.

With only very light edits made (for clarity) to my transcribed interview with him by telephone, I give you the take of Dr. Sievenpiper on fructose in his own words:

DD: What did you think of the debate in San Diego? Do you think it helped clear up confusion among the scientists about the state of evidence on sugar and, particularly, fructose? 

JS: I absolutely did. It was a very useful debate just because I think the debate to this point has been dominated by people like Dr. Lustig. I have a lot of respect for and certainly am on friendly terms with Dr. Lustig. We have had very cordial and academic discussions in email and when I've spoken with him. We obviously disagree where the data lies. Unfortunately, I think he's done a better job at knowledge translation than the people on the other side of the argument. Certainly, I'd say I’m not on the other side of the argument. I'm in the middle of the argument trying to make sense of it. Having both sides better represented was far more balanced than what came out of his two-million hit sensation on YouTube and a lot of the media coverage that has resulted from that of Gary Taubes and some others as a result of that video.

DD: Where do you think there's still confusion? Where is the real scientific debate?

JS: The confusion really lies in that a lot of this debate has been underpinned by the animal literature and ecological studies without recognizing the flaws and translating that information into real-world human scenarios. The problem has really been with someone like Lustig who can run through the pathways at very impressive clip and can convince someone that, OK, there's so much biological plausibility, so it must be true. People aren't asking the question, "Well is it? What happens when we do look at humans? Do we actually see this signal?"

What we're finding with our meta-analyses is that, no, we don't see that signal. Or, we do where energy is part of the equation and seems to be dominant. I think that is the disconnect that has really come because of the use of the animal data and ecological analyses. It's very seductive. Because they do show reproducible, consistent effects of a harmful signal.

DD: You're saying that signal isn’t something that was found in humans per your meta-analyses on isocaloric trials in humans?

JS: Correct. That was the reason we did the meta-analyses in the first place. We didn't set out an a priori hypothesis that fructose doesn't do these things. In fact, our hypothesis would've been "Well, everyone's talking about it. The animal data is suggestive of an adverse effect of fructose." If anything, our hypothesis was that there's going to be an adverse effect.

We set out to do these meta-analyses to answer that question – whether that phenotype that we see in animals that can be so robustly reproduced, the signal we're seeing from ecological data (where we are looking at populations), and whether that actually translates into human models where we actually feed people and control for all extraneous variables.

We decided to use the gold standard or highest level of evidence in nutrition or, really, in most fields -- which is controlled trials; and, in nutrition, is controlled dietary feeding trials. We wanted to apply the best tools we have, which was systematic review and meta-analyses tools to synthesize that knowledge and information to try to answer the question.

Is it true? What we found was that it wasn't. We looked at bodyweight -- which is the Annals [of Internal Medicine] data that you're aware of -- in each case there was no effect of fructose when it was isocalorically exchanged. There was no adverse effect on bodyweight, blood pressure, or uric acid. We do see a very consistent and strong effect on bodyweight when fructose is providing excess energy.

DD: The strong effect on bodyweight was in comparison to other carbohydrates?

JS: That's comparison to a control diet. The fructose is providing excess energy. Is it the fructose you're adding? Is it the energy from fructose? Those are actually difficult to interpret. What we found is that the energy is dominant when you look at neutral, positive, or negative energy balance studies. We found that as long as fructose was isocalorically exchanged, there was no effect. Fructose wasn't having an effect beyond energy. Our conclusions looking were that energy appears to be dominant in particular case to bodyweight. The bodyweight increase we saw was predicted by the energy was consumed. We would say the same thing, although we didn’t have as many studies, for uric acid. In our lipid analyses, we find the same thing again. Energy is dominant.

DD: Let me ask a question about those hypercaloric trials in relation to animal studies and the flaws of which you speak. Recently, for example there was what I call the "sugar makes you stupid" study [covered here]. When I read it, I found it was simply a hypercaloric trial where rats were given fructose in addition to a control diet, which led to insulin resistance. 

JS: I think you hit the nail on the head. There is really the disconnect between animal carbohydrate metabolism and human carbohydrate (or fructose) metabolisms. One of my criticisms of using animal data is that they feed at superphysiological levels at 60 percent energy. No one is consuming that.

The 50th percentile for intake in the United States is 49g per day, which is just a little less than 10 percent per day of energy from fructose. We're talking of a six-fold difference in what people are really consuming and what these models are feeding. If you look at even the 95th percentile for intake of fructose in US population from using NHANES data, the 95 percentile for intake for NHANES for fructose consumes 87g of sugar or little less than 20 percent energy. (NHANEs is intake data as opposed to disappearance data, what the USDA collects, which is just availability of sugars, but tends to overestimate because it doesn't account for waste; it looks at how much went onto the market; when you only fill your coffee half full with that sachet of sugar and throw away the rest, it doesn't count for how much was thrown away). So these models are feeding even three-fold, if we're generous, compared to the 95th percentile of the population are consuming, which is really super-physiologic. Just based on the feeding pattern and paradigm of those models, you can't equate them.

On top of that, we know that if you look at comparative physiological studies, animals metabolize carbohydrates differently than do humans. In animals on a high-carbohydrate diet not providing excess energy, you find that de novo lipogenesis [conversion by the liver to fatty acids] is anywhere from 50 percent or higher. They basically make fatty acids for at least 50 percent of the carbohydrate [consumed]. De novo lipogenesis accounts for at least 50 percent carbohydrate. In humans, it is very, very hard under isocaloric (neutral energy) conditions, let alone in overfeeding conditions, to push that beyond 10 percent or even 20 percent.

A lot of the outcomes that have been implicated, have really centered on this hypothesis of de novo lipogenesis. I have a really big problem when people want to extrapolate from an animal study where their feeding (1) superphysiological amounts of fructose and (2) in a model where the metabolism is not the same as in humans – it's very different. It's bad for rats or mice (you name your study and adverse effect of fructose), but it doesn't mean that's the case in humans. Again, that's the reason why I think we need good human data and that's why we wanted to synthesize the human data. We do have almost 50 controlled feeding studies on different questions related to cardiometabolic control.

DD: At Experimental Biology, Dr. Rippe argued that the amount of de novo lipogenesis in humans was pretty negligible in response to fructose eaten normally in the U.S. Can you comment on what he shared? 

JS: That is correct. If you actually look at the animal studies where you feed them high fructose, you make this beautiful metabolic syndrome phenotype (where they have very high TGs, low HDL, hypertension, obesity, and insulin resistance). We don't see that in humans. It doesn't hold true because when you actually look at carefully conducted studies.

Dr. Rippe was actually quoting Luc Tappy's work. He has put together a really excellent review of his own work and that of others who've done careful stable isotope tracer studies where you can label acetate, fructose, and different metabolites. You can see where fructose is going and where fructose is ending up. What he's found is that with a fructose load 50 percent goes to glucose, about 25 percent goes to lactate, greater than 15 percent and up goes to glycogen, the remainder would be oxidized directly [going to CO2 through the TCA cycle], and a small portion contributed to de novo lipogenesis. I can't remember what Dr. Rippe had on his diagram, but even as low as, let's say, 3 percent, it is really quantitatively non-significant. In animals, de novo lipogenesis is quantitatively significant. It doesn't appear in humans with high-carbohydrate feeding and the same is true even under high-fructose feeding. We see this very robust de novo lipogenesis in animals. We don't see it in humans.

That I think is a problem because this is one of the underpinning mechanisms by which antagonists like Dr. Lustig and others are hanging their arguments in terms of why we're seeing an increase in overweight and obesity, metabolic syndrome, diabetes, and the metabolic syndrome phenotype in general that fructose is thought to elicit.

DD: Why do you think Lustig continues to argue that de novo lipogenesis makes fructose intake a metabolic danger?

JS: When you look at someone like Rob Lustig, who, again, I actually I have a lot of respect for because I think he's well-intentioned and he's sincere about his belief. But I think his passion and enthusiasm in this area are clouding his judgment a bit. You could say the same for Gary Taubes or anyone who has kind of taken a very extreme position on the data.

If you look at the data carefully, sort out the wheat from the chaff, and look for the well-controlled data to drill down on some of these mechanisms -- OK, let's look in humans and not animals; let's look under basic normal energy balance conditions, and let's use the best or most elegant tools we have, which are stable isotope tracers -- this is the answer you get: 50 percent glucose, 25 percent lactate, greater than 15 percent to glycogen. These may vary a bit just based on the rest of the background diet and activity level of the organism or human in this case. But in general, this is the fate of fructose.

It's not what Dr. Lustig and others would have you believe -- massive influx into de novo lipogenesis to hugely raise triglycerides, overweight, obesity, metabolic syndrome. You don't see it through this mechanism. We just don’t see the signal of increase in bodyweight or even for triglycerides; only the very high doses.

DD: What about a possible benefit from fructose? For example, in one of your meta-analyses you found a benefit on glycemic control. 

JS: The study you're quoting, or the meta-analysis we did, was looking at so-called small or catalytic doses of fructose at a level that would be obtainable from fruit (so, basically, less than 10g per meal). We took that to mean 36g per day (meaning 10g per meal and two snacks with 3g each; like 30 percent of a meal). That's how we came up with eligibility criteria for that meta-analysis. That was just a snapshot that looked at low doses of fructose.

We saw this benefit for hemoglobin A1c (HbA(1c)) -- almost a 0.5 percent reduction. That's a 0.5 percent absolute reduction (not a proportion) similar to what you would see with antidiabetic agents at the lower range of efficacy. And, we saw that without adverse effects on triglycerides, body weight, insulin, and uric acid. So, we concluded that there was an overall a net metabolic benefit from these low doses of fructose at a level really that is obtainable from fruit.

That correlated quite nicely with what we saw in a very large glycemic index trial we published in patients with type 2 diabetes. What was the most important low-glycemic index food item that best predicted reduction of HbA(1c)? It was low-glycemic index fruit. The level of fructose that you would've obtained with the most commonly consumed low-glycemic index fruit (apples, it turns out) would be 10g per serving. So it fit nicely with this idea of this catalytic dose of about 10g per meal. And in that study we saw an identical 0.5 percent reduction of HbA(1c) units. So, further confirming that there may be something to fruit.

DD: How will a metabolic benefit from fructose change the debate?

JS: Part of the issue is about balancing the argument. I think we can learn a lot from someone like Robert Lustig because he has done the knowledge translation piece so well. Whether he's done it intentionally or not, he has brought a lot of attention to his issues. On the other hand, we’ve done -- at least the people with a more balanced view -- a very poor job at trying to communicate that balanced view. Yes, there may be some signals [that fructose has an adverse effect] or, no, there aren't, or it may be conditional on energy. With all the nuances, we’ve done a pretty bad job at communicating it as opposed to the simple message of "Fructose at any level is poison." We're trying to say it depends on the dose, it depends on the energy, and that’s a hard message to communicate. We've been dwelling on harm. We’ve been saying "Well, it doesn’t support harm except where there is excess energy."

The nice thing about the glycemic control outcome is that we can actually talk about benefits. We can switch that argument back on its heel in a way to say, "Yeah, there's issues around harm. We need to really find out where the dose response lies." Now, we can start talking about a benefit. We can start talking about a level of fructose at a dose and where do we see a benefit without adverse effects which we may see at very high doses. And we can go back to moderation and even moderation having a benefit. As Dr. Klerfeld put so nicely [quoting Paracelsus, "The dose makes the poison"], the toxin is determined by the dose. Even water is toxic if you drink too much of it.

DD: In response to Dr. Lustig in Nature, you commented about fruit fructose. Similarly, you commented to me at the symposium in San Diego that you had a concern that unwarranted fears of fructose would lead to reduced intake of fruit.

JS: Again, part of the reason Dr. Lustig and Gary Taubes are so good at getting this message out is that it's so one-sided, very easy, very palatable message. They've oversimplified it so much where there is no level of safe intake, that it is a poison, that it should be just like tobacco (to paraphrase what he says in his video), and that it should be regulated accordingly. He doesn't say it so much in his Nature piece.
But he doesn't actually talk about dose, where the dose response lies, and he doesn't address fruit, which may be a healthy form (I think should be an uncontroversially healthy form) of fructose. The problem with these arguments and these very extreme positions is that we don't talk about dose and we don't talk about the form of fructose.

That's the danger -- that people will say that fruit is a source of fructose and I won't consume fruit because it may induce obesity, metabolic syndrome, and so on. It's not just the lay public that may take this message to heart but professionals. We had an endocrinologist here at our hospital at University of Toronto who was telling patients not to consume fruit because of the fructose content precisely because of all the commentaries, editorials, and reviews that Rob Lustig had been publishing. The danger is that people will take the message to extreme. They'll start saying "I should cut these things out (apples, pears) to cut my fructose exposure." That is a really wrong-headed approach. When I talk to Dr. Lustig on the side, I do get a sense that he does think that there's a dose threshold, but it doesn't come out in the writing, or the YouTube piece.

DD: I've heard about similar situations happen where people are cutting out fruit and taking Lustig's message to the extreme. Dr. Sievenpiper, you've given me, us, people a lot to think about. I appreciate your time.  

Note: When I reached out to Dr. Sievenpiper, he was gracious enough to point me to a just-published "lovely, balanced, well-written paper" by respected physiologist Luc Tappy of Université de Lausanne, in Switzerland. The paper, Dr. Sievenpiper said, summarized much of Dr. Tappy's own take after the event in San Diego and would help answer more questions. (The open-access paper can be found here.)

Monday, May 21, 2012

Rice consumption and health

Carbohydrate-rich foods lead to the formation of blood sugars after digestion (e.g., glucose, fructose), which are then used by the liver to synthesize liver glycogen. Liver glycogen is essentially liver-stored sugar, which is in turn used to meet the glucose needs of the human brain – about 5 g/h for the average person.

(Source: Wikipedia)

When one thinks of the carbohydrate content of foods, there are two measures that often come to mind: the glycemic index and the glycemic load. Of these two, the first, the glycemic index, tends to get a lot more attention. Some would argue that the glycemic load is a lot more important, and that rice, as consumed in Asia, may provide a good illustration of that importance.

A 100-g portion of cooked rice will typically deliver 28 g of carbohydrates, with zero fiber, and 3 g of protein. By comparison, a 100-g portion of white Italian bread will contain 54 g of carbohydrates, with 4 g of fiber, and 10 g of protein – the latter in the form of gluten. A 100-g portion of baked white potato will have 21 g of carbohydrates, with 2 g of fiber, and 2 g of protein.

As you can see above, the amount of carbohydrate per gram in white rice is about half that of white bread. One of the reasons is that the water content in rice, as usually consumed, is comparable to that in fruits. Not surprisingly, rice’s glycemic load is 15 (medium), which is half the glycemic load of 30 (high) of white Italian bread. These refer to 100-g portions. The glycemic load of 100 g of baked white potato is 10 (low).

The glycemic load of a portion of food allows for the estimation of how much that portion of food raises a person's blood glucose level; with one unit of glycemic load being equivalent to the blood glucose effect of consumption of one gram of glucose.

Two common denominators between hunter-gatherer groups that consume a lot of carbohydrates and Asian populations that also consume a lot of carbohydrates are that: (a) their carbohydrate consumption apparently has no negative health effects; and (b) they consume carbohydrates from relatively low glycemic load sources.

The carbohydrate-rich foods consumed by hunter-gatherers are predominantly fruits and starchy tubers. For various Asian populations, it is predominantly white rice. As noted above, the water content of white rice, as usually consumed by Asian populations, is comparable to that of fruits. It also happens to be similar to that of cooked starchy tubers.

An analysis of the China Study II dataset, previously discussed here, suggests that widespread replacement of rice with wheat flour may have been a major source of problems in China during the 1980s and beyond ().

Even though rice is an industrialized seed-based food, the difference between its glycemic load and those of most industrialized carbohydrate-rich foods is large (). This applies to rice as usually consumed – as a vehicle for moisture or sauces that would otherwise remain on the plate. White rice combines this utilitarian purpose with a very low anti-nutrient content.

It is often said that white rice’s nutrient content is very low, but this problem can be easily overcome – a topic for the next post.

Sunday, May 20, 2012

Have a cuppa pesticide and #dontdestroyresearch

Earlier today, biologist Mary Mangan (@mem_somerville) shared the bad news that anti-biotechnology activists had succeeded in breaking into and damaging a publicly funded research project at Rothamsted Research Station in Harpenden, England. The vandalism happened only a week ahead of a planned demonstration organized by the Take the Flour Back environmentalist group (which I wrote previously about here).

Mangan wrote on her Google+ page:
Sadly, the destruction has begun. Forces opposed to science have vandalized a research project in the UK that has been underway for many years. It is a publicly funded project, and it attempts to use a biological method of control of insects on wheat plants. It could someday help reduce the use of pesticides and improve food security.
This led to a series of comments from people who mostly expressed sadness and anger about the damage. But, then, there were both of these comments:

Thank god for this!!! GMO anything is not healthful to the environment or to us as humans! You are altering the genetic chemistry of that plant and when it cross-breeds with another plant (yes I said when), that one now has insect resistance, and soon insects will develop a way to eat these plants and then we're back to square one, but worse for wear because now we have to come up with some new ingenious way to keep insects from eating our crops.
We may have been altering the genetic makeup of plants, but only through natural selection and never through any artificial genes that were never supposed to exist in a specific species. Insect resistance is not a gene normally found in any living plant species that I know of. There are poisonous plants which I suppose could provide insect resistance, but you don't see them cross-pollinating with any other species that we eat.
That's when Mangan, as she puts it, spit out her "carcinogen-laden coffee" and decided to "help this person understand the reality."

Clearly, what the person above didn't understand while making these comments, is that plants have been in arms race with pests for millenia. Part of a plant's defense are often thousands of natural pesticides, insecticides, and herbicides. It's a common misconception that "all-natural" and "organic" means "free of pesticides." They may simply mean not grown with synthetic pesticides, although organic crops are often grown with plenty of organic pesticides, and are likely to contain more naturally produced pesticides than conventionally grown plants.

I might've also made light of the situation with this person, as I have to others with similar arguments, that pesticides shouldn't always be thought of as a "bad thing." After all, humans have long enjoyed consuming pesticides with glee (healthy and nonhealthy). For example, Mangan alluded to the fact that caffeine and other bitter compounds in a cup o' joe are themselves, in fact, natural pesticides. The coffee plant produces them with intent of simply repelling, paralyzing, or killing insects. Resveratrol and piceid, the bitter stilbene compounds produced by grape skins in response to stress, are pesticides that end up contributing to the flavor of red wine (and they may account for some of its health benefits). There's also tetrahydrocannabinol (THC), the psychoactive compound of cannabis, a pesticide that some enjoy along with a load of carcinogenic compounds. Nicotine, too, is a natural pesticide from tobacco.

In response to the uniformed comments, Mangan posted links and quotes about plants producing their own pesticides naturally. That's when I joined the conversation, via Twitter, because I thought it would be a good idea to house a few of the links relating to natural pesticides in one place. Graciously, Mangan put her bookmarks together and posted them all on the Biofortified forum entitled "Plants making pesticides". It will be useful for helping educate people about naturally produced plant pesticides. In the forum post, she includes references to work from biochemist Bruce Ames, who famously triggered controversy by writing:
We calculate that 99.99% (by weight) of the pesticides in the American diet are chemicals that plants produce to defend themselves. 
Getting back to the purpose of this post -- there needs to be more intelligent conversation about pesticides. Without doubt, there's a need to reduce use of pesticides on plants to protect biodiversity. The overuse of pesticides and herbicides, unfortunately, kills off both harmful and beneficial insects and plants and can lead to pest resistance.

Overall pesticide reduction is what makes the Rothamsted research so important. The publicly funded project tests a variety of wheat genetically engineered with a mint compound that leads to emission of a pheromone that acts as a aphid repellent. As a crop, wheat is one of the world's most important crops and an aphid-repellent variety could significantly reduce pesticide use across the globe.

These are the reasons why I signed the Sense about Science petition to support the appeal scientists at Rothamsted.    

EXCLUSIVE: FREE PUBLIC LECTURE with Richard Cork - David Beckham - Sex and Politics - Competitions, Films and New Arts/Health Tender in Cumbria...

What a speedy couple of weeks: Richards show is down, the Royal Northern College of Music have had the most excellent two day conference on Music and Health, at which I was privileged to share the manifesto.  It was a conference full of passion and possibility and I am thrilled to have hooked up with Musique et Sante once more - exemplars, who alongside Holly and her colleagues, really work out the synergies between notions of music therapy and music and health, and for me, the political power of music for the individual and society. Brilliant and inspiring. Thank you.

Thinking no doubt, about the Olympic Flame and its progression through our bunting filled cities and villages, I dreamt last night of David Beckham, proudly pounding the pavements, torch held high in honour of Queen and country. Only, as in all good dreams, he shouts ‘flame on’ and takes off into the night sky, (St Beckham of Trafford in ascension) to fall to the earth seconds later, like some tousled Icarus - some spluttering spitfire, shot down and impotent. I rush over to him, only to find it's not his coiffured broken body, but that of humiliated and impoverished street vendor, Mohamed Bouazizi who self-immolated in Tunisia and kick started what we now call the Arab spring.

And with my increasingly inflamed feelings of patriotic positiveness to the Jubilee and Olympics, I’m thrilled to note that the once vilified athlete, John Carlos (who alongside his fellow American Tommie Smith, so splendidly drew global attention to inequalities in the US by bowing their heads and raising their black-gloved hands in salute on the winners podium in the ‘68 Olympics) is in Liverpool on the 26th May at 6:00 at FACT, in conversation. 
(details here: )

He comments, "Coming to the UK on the eve of the Olympics is a very exciting opportunity for me to talk with the new generation about why we did what we did back in 1968. When Tommie Smith and I raised our fists on that medal platform at the Olympics, we knew that we would catch hell but we didn't care. We didn't care because we wanted the coming generations to live and breathe as full citizens with equal rights. I was just concerned with right and wrong. We went out there for humanity. We are here 43 years later because the fight is still to be won." 

To make a very unsubtle segue between Carlos and the potency of music, here’s a beautiful piece of music by Marvin Gaye that needs no introduction: loaded, potent and sublime:  What’s Going On?

Building further tenuous connections between 1968, and current olympic-sized spending in a time of austerity and inequality - step forward French philosopher Alain Badiou who in his new book, Polemics makes interesting connections between sex, love and politics. Here’s a quote from an article in Saturday’s Guardian -

He defines his "real politics" in opposition to what he calls "parliamentary cretinism". His politics starts with subjective experience, involves a truth procedure and ends, fingers crossed, in a communist society. Why? "It's necessary to invent a politics that is not identical with power. Real politics is to engage to resolve problems within a collective with enthusiasm. It's not simply to delegate problems to the professionals. Love is like politics in that it's not a professional affair. There are no professionals in love, and none in real politics." 

...and finally, (before we get to the opportunities and events) in the presentation of my paper,  A Brightly Coloured Bell-Jar, I’d discussed the role of psychiatry, in the demonisation of people who are gay, reducing people to morbidity and pathological disfunction in secular society.  Well the psychiatrist Dr Robert Spitzer, (and architect of modern classification of mental disorders) the name behind research that posited that gay people could successfully become straight if they were motivated to do so: has retracted his long-held claim. More than that, he has apologised. I quote: "I believe I owe the gay community an apology...I also apologise to any gay person who wasted time and energy undergoing some form of reparative therapy because they believed that I had proven that reparative therapy works."

OK...back to business.

I am thrilled to announce that Dr Langley Brown has been appointed as Research Associate and will be working with me on new research in Arts and Health. One of Langley’s first coups has been to secure a free public lecture by acclaimed art critic Richard on...

Arts for Health presents:
The Healing Presence of Art
A History of Western Art in Hospitals
An illustrated lecture by acclaimed art critic and author
Richard Cork
on his new book of the above title, followed by a discussion
6.30 pm, Wednesday 13th June 2012
Lecture Theatre LT3, Geoffrey Manton Building,
All Saints Campus, Oxford Road, 
Manchester Metropolitan University, Manchester, M15
The event is free, but booking strictly in advance:

To celebrate the first year of the Arts for Health Archive, and to help place contemporary arts and health practice within a long-standing yet little-studied tradition, Arts for Health has invited Richard Cork to talk about his new and beautifully illustrated book on the history of western art in hospitals. His lecture will be of interest to anyone concerned with the arts, the human environment, and wellbeing.

Between birth and death, many of life's most critical moments occur in hospital, and they deserve to take place in surroundings that match their significance. In this spirit, from the early Renaissance through to the modern period, artists have made immensely powerful work in hospitals across the western world, enhancing the environments where patients and medical staff strive towards better health.

Distinguished art historian Richard Cork became fascinated by the extraordinary richness of art produced in hospitals, encompassing work by many of the great masters - Piero della Francesca, Rogier van der Weyden, El Greco, William Hogarth, Jacques-Louis David, Vincent van Gogh, Frida Kahlo and Diego Rivera, Fernand Leger, Marc Chagall and Naum Gabo. Cork's brilliant survey discovers the astonishing variety of images found in medical settings, ranging from dramatic confrontations with suffering (Matthias Grunewald at Isenheim) to the most sublime celebrations of heavenly ecstasy (Giovanni Battista Tiepolo in Venice). In the process, he reveals art's prodigious ability to humanize our hospitals, alleviate their clinical bleakness and leave a profound, lasting impression on patients, staff and visitors.

Richard Cork is an award-winning art critic, historian, broadcaster and curator. Formerly Art Critic of The Evening Standard and Chief Art Critic of The Times, he now writes for The Financial Times and broadcasts regularly on BBC radio and TV. He was Slade Professor of Fine Art at Cambridge University in 1989-90, and Henry Moore Senior Fellow at the Courtauld Institute, 1992-5. He has acted as a judge for the Turner Prize and curated major exhibitions at Tate, the Hayward Gallery, the Barbican Art Gallery, the Royal Academy and other European venues.

Cork’s many books include a ground-breaking study of Vorticism, awarded the John Llewellyn Rhys Prize in 1977; Art Beyond the Gallery, winner of the Banister Fletcher Award in 1986; a major monograph on David Bomberg, 1987; A Bitter Truth: Avant-Garde Art and the Great War, winner of the Art Fund Award in 1995; Jacob Epstein, 1999; four acclaimed volumes of his critical writings on modern art, 2003; Michael Craig-Martin, 2006; and Wild Thing: Epstein, Gaudier-Brzeska, Gill, 2009. He was appointed an Honorary Fellow of the Royal Academy in 2011.

"A comprehensive and magisterial monograph... Cork brilliantly conveys the extent to which hospitals provided a public arena for the display of art, long before the existence of museums."—Charles Saumarez Smith, RA Magazine

"There have been many studies linking aspects of art and illness but Richard Cork’s scholarly and elegant book is the first to show just how closely the two have always been intertwined and just how various have been the responses."—Michael Prodger, Literary Review

"Cork's prodigiously researched book documents how art in hospitals developed and provides a solid foundation for its future role."—Colin Martin, World Health Design

Pallant House Gallery presents the launch of Outside In: 2012, a unique open-entry arts prize for Outsider and marginalised artists. Submissions remain open until 20 July 2012. Selected works will be showcased in a major exhibition at Pallant House Gallery in Chichester, West Sussex from 27 Oct 2012 – 3 Feb 2013.

LA COLIFATA (gracias D.P)

Película documental dirigida por Carlos Larrondo. Producida por Bausan Films y Filmanova Invest. LT22, Radio La Colifata es una radio hecha íntegramente por los internos del Hospital Psiquíatrico J.T. Borda de Buenos Aires. Se graba y se emite desde los jardines del Hospital; se escucha en todo el mundo. Una radio que cuestiona el limite entre locura y razón. Una radio que rompe el muro que separa cuerdos de locos Se da la palabra a quienes la han tenido negada por mucho tiempo: los locos, que, además, pueden mostrarnos todas esas cosas que nosotros los cuerdos, no somos capaces de ver.

Here is an 8 minute short film, shot on location at Alder Hey Children's Hospital by long-time Arts for Health collaborator, Hafsah Naib and which features patients performing ideas about medicines of the future. The participatory and engagement technique used to generate child-led authentic performance is based upon an artistic approach that she has been developing for several years and which has been the subject of collaborative and academic research presented at art and education conferences in Japan, Austrailia and more recently Hungary.

Copeland Borough Council are seeking expressions of interest from organizations or groups who have an interest in tendering to continue delivering the Pathways to Art project and who can fulfill the following criteria:
  • The aims and objectives of the organisation must reflect those of Pathways to Art.
  • There must be a legal framework and constitution in place which will allow applications to various grant/funding bodies.
  • Demonstrable experience of successful funding applications.
  • Members of staff working on the project must have demonstrable skills in project management in the arts and delivering arts workshops with clients who have mental and/or physical health problems.
Project Summary
The Pathways to Art project has been successfully operating in West Cumbria since 2007, although in the last year it has been running in Copeland Borough only due to budget constraints. The changing economic climate means it is no longer viable for the project to continue operating within the Local Authority, however Copeland Borough Council recognise the benefits of the project to its residents and to that end wish to see it continue, either as a project of an existing organisation or by a group who are interested in establishing the project as a Social Enterprise in its own right.  In order to assist this, the council is offering a one- off grant of £15,265, which is mainly, matched funding for further grant applications.

How to Apply
Through an expression of interest which outlines:
How you meet the criteria defined above, including CV's of any staff working on the project, both initial planning/fundraising and workshop delivery.
Why you are interested in this opportunity.
Initial ideas for running the project in the first instance and how you might develop it over 3 years, bearing in mind the following:

Contract NWCE-8U5MWK
Title Project 611: Pathways to Art
The tender will go live today ( 16 May 2012) at 14.00pm on The Chest ( organisations or groups wishing to tender will need to register on The Chest which is free. All relevant guidance and documents are on The Chest and expressions of interest should be submitted through The Chest no later than 17.00pm on Friday 8 June 2012.

The UK Medical Collections Group
Thackray Museum, Beckett Street, Leeds, LS9 7LN
This inspiring and practical one-day conference will bring you up to date with new structures and priorities in the health sector, and will explore how heritage organisations can contribute to government agendas around all aspects of health.  Whether you are already involved with the UK Medical Collections Group, or if you are a curator or educator who is keen to join the debate about what heritage can offer to health, we hope that you can join us on 29th May.  You will hear from speakers from the heath sector, as well as museum and arts professionals who have worked towards health agendas. You will also have the chance to explore how you can link your work to health outcomes. We aim to bring together existing practice and new information to develop a long-term vision of how museums can contribute to health outcomes.

Tuesday 29th May, 201210am-4pm
For enquiries or to make a booking, please email:

Thank you as ever...C.P.