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Monday, February 27, 2012

Sugar ~ Pure, White and Misunderstood

Few of the nutrients in food attract a more negative agenda than sugar. I recall early in my career a famous or, in hindsight, an infamous book entitled “Pure, White and Deadly” written by John Yudkin, then Professor of Human Nutrition at the University of London. Not a year has gone by since then, that sugar and its attendant industry, has not been strapped to the whipping post for a thorough reminder of its evil properties. One of the most recent was a ‘Comment’ in Nature which equated sugar with alcohol as a substance of abuse and addiction meriting the guiding hand of Miss Nanny State to help us free ourselves of its dangers, through tax and other regulatory measures. In relating sugar to alcohol, the first parallel is that there is now unfettered access to a high sugar diet, which according to the authors, is a new phenomenon. They write thus: “First, consider unavoidability. Evolution­arily, sugar was available to our ancestors as fruit for only a few months a year (at har­vest time), or as honey, which was guarded by bees. But in recent years, sugar has been added to nearly all processed foods, limiting consumer choice”[1].   If I got that in an essay from an undergraduate, I would have annotated it with the letters “WTF”. (If you don’t get that, then simply Google it [2].)

The missing bit is somewhere in between “our ancestors” and “in recent years”. Honey, was one of the great luxury foods, bees or no bees, for centuries. Virgil wrote about it thus: “Next I come to the manna, the heavenly gifts of honey…one that can load me with fame”. The God Zeus was fed from childhood on honey. Sugar cane came later but well over 1,000 years ago, first recorded in T’ang dynasty (AD 766 to 790). The first known industrial sugar cane refinery was built on the Greek island of Crete in 1000 AD, the island of Crete being known as Qandi in Arabic, hence the name Candy[3] (bet you didn’t know that)!!!  So sugar didn’t suddenly appear in the last few decades.

One of the problems linking sugar with health is that the term sugar is a chemical term referring to a very specific group of chemicals called “saccharides”: “Any of a series of compounds of carbon, hydrogen, and oxygen in which the atoms of the latter two elements are in the ratio of 2:1, especially those containing the group C6H10O5”. Glucose is the most abundant saccahride and because it is alone, single in the sugar world, it is a monosaccharide. Fructose is next and then we meet disaccharides where sugars are paired off. The most abundant pairing is glucose with fructose and that is what we know as “sugar”, in the sense of the white crystalline material in the sugar bowl. Simple? You would think so but my UK colleagues have managed to create quite a complex issue from this, fortunately not followed by many other countries. Let me explain. Here I am at my breakfast table. In front of me is a bowl of oranges, which contains one less orange that two minutes earlier, since I took one of the oranges, cut it in two and used a manual juicer to extract the juice. That juice is in a glass on my right. Now according to the UK authorities, the sugar in the orange in the bowl in front of me is an “intrinsic” sugar, a natural part of the plant. The fact that I made juice from it means I changed the sugar from being intrinsic to being “extrinsic”, that is a sugar outside its natural plant environment, which now lies in the glass to my right. The UK decision to adopt these definitions was not based on extensive epidemiology, which showed that intrinsic sugars were “good” and extrinsic sugars were “bad”. Rather, it was based on the general negative nutritional view among some (ideological rather than scientific in my analysis) that “sugars are just plain bad” and the need to square that stance with the belief that some foods, which were definitely “good”, such as fruits had sugar in them. So there had to be good sugars  (intrinsic) and bad sugars (extrinsic).

When the epidemiological evidence linking sugar intake to obesity emerged as completely inconclusive, a new concept evolved to the effect that glucose, one item of the sucrose pair, was probably ‘ok nutritionally” (they had little choice here since starch is digested and absorbed as glucose and starch was a very “good” carbohydrate) but that the other half of sucrose, namely fructose was the real culprit.  According to the Comment in Nature, sugar compares almost precisely with alcohol in its effects on humans. In a table entitled “Excessive consumption of fructose can cause many of the same health problems as alcohol” they list conditions such as high blood pressure, heart disease, impaired glucose function, obesity, pancreatitis, liver disease (fatty liver) and addiction (habituation) to chronic fructose intake. Frankly, these are extreme views based largely on (a) the extrapolation of animal studies with extreme diets to humans and (b) association studies in human nutrition epidemiology, which have not been subject to verification with dietary intervention studies. Take one example, chronic fructose intake and obesity. A major study, which reviewed all known intervention studies (n=41 studies) of the chronic effect of dietary fructose on obesity in humans, was recently published by some of the world’s most respected specialists in carbohydrate nutrition, a study fully funded by the Canadian Institutes of Health Research with zero industry funding[4]. I report their conclusion in full: “Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories. Free fructose at high doses that provided excess calories modestly increased body weight, an effect that may be due to the extra calories rather than the fructose”. So this independent review of the direct effect of chronic intake of fructose on obesity finds the villain innocent. Will that placate the naysayers of sugar in human nutrition? Not at all. However, I would once again remind them of my favourite quotes to those who resolutely adhere to pet theories. Addressing the Assembled Church of Scotland, Oliver Cromwell exorted them so: “Gentlemen, in the bowels of Christ, I beseech thee, think it possible you may be wrong” or Sir Peter Medawar, Nobel Laureate in immunology who wrote in his book “Advice to a young scientist”: “The intensity with which an hypothesis is held to be true has no bearing on its validity”. And finally, from Professor Rose Frisch, the subject of last week’s blog whose work was always controversial when she was asked how did her work finally reach acceptance, she replied: “Funeral by funeral”!!

Whipping sugar is popular. It makes people feel good, it is good media friendly and it is a joy to ministers for health who would rather discuss anything bar waiting lists.  But it is rooted in atrocious science with one exception, dental caries. Sugar is to be enjoyed and if you’re watching your weight, artificially induced sweeteners are to be enjoyed. My religious friends tell me, that sugar hasn’t yet reached the sinful threshold.

[1] Lustig, RH et al (2012) “The toxic truth about sugar”. Nature, 482, 27-28
[3] “History of Food” by Maguelonne Toussaint-Samat, Blackwell, Oxford
[4] John L. Sievenpiper, et al (2012) Effect of Fructose on Body Weight in Controlled Feeding Trials - A Systematic Review and Meta-analysis. Ann Intern Med. 156:291-304.

Monday, February 20, 2012

Female fat and fertility

Female fat and fertility[1]

For most females, fat is a nuisance. Like a bad guest, it arrives apparently uninvited, lingers far too long and is hard to get rid of. There is a certain level of body fat that each woman would like and it is that level of fat that makes her feel and look good. Whereas today we view female fat in terms of style and fashion, in times gone by, female fat dominated the subject of fertility. Most of the ancient symbols of fertility, such as the 30,000BC Venus of Willendorf, were of seriously fat women.  The conclusion of a successful pregnancy requires about 50,000 calories over and above normal daily living and exclusive breast feeding, the only option in times gone, by requires about 500 to 1000 additional calories every day. Unless women have some fat reserves to take this task on, bearing in mind that food might become in short supply during pregnancy, then it is not wise to travel down this reproductive road. It isn’t as though women have to make a difficult decision themselves. Nature does it for them.

The first road to fertility begins with the onset of menstruation or menarche.  In the middle of the 19th century, the mean age for menarche was 17 years. A century later that had fallen to 14.5 years and in the US it now stands at 12.8 years[2]. These changes are due to improved nutrition resulting in young girls reaching the magic number at an earlier age. That magic number relates to body weight and the actual magic number is 46.7 kg (103 pounds). During their growing up period, children grow in a fairly linear manner (not withstanding the comments of aunts and uncle’s that “My, hasn’t she just shot up”). In today’s terms, at or around 9.5 years on average, a major growth spurt occurs in young girls. In addition to the laying down of the female reproductive tissues, there is a sudden spurt in the laying down of fat. About 2 years later, this dramatic growth spurt slows down (no one knows why) and about 6 to 8 months later, menstruation begins. Most of these data are based on detailed longitudinal studies of growth in US girls in Berkeley, Boston and Denver between 1940 and 1950. Some girls reach menarche earlier and some later, that being a feature of normal distribution. Irrespective of when they reach menarche, the magic figure of 103 pounds or 46.7 kg also applies. In fact this figure really translates into an average of 22% body fat and it is this fat content that determines whether or not menarche begins.

In today’s world with an obsession about body fat and fitness, many women fail to menstruate because their body fat falls below the critical level. That ancient safety valve that spared women with inadequate nutrient and energy reserves from becoming pregnant still kicks in. Now we know the biochemistry a bit better. Fat contains an enzyme aromatase, which converts a weak male androgen into estrogen, a key female reproductive hormone. Prior to menopause, one third of all estrogen in circulation in females is thus derived. With the onset of the menopause, this rises to 100%. The second key biochemical force to be reckoned with is the protein leptin, secreted from fat. Leptin suppresses appetite and thus the fatter we are, the more leptin we produce and thus the greater the suppression of appetite. We now know from human genetics studies, that a deficiency, relative or absolute of leptin in young girls, totally negates any sexual development. Leptin and related hormones secreted from the adipose tissue form the signal between fatness and fertility sending signals to that part of the brain most involved in sexual development.

The power of body fat levels to shape the female body can reach quite disturbing levels. Young girls, who show a precocious talent for ballet, are known to follow a restricted diet during their strict training to keep their weight as low as possible. Normally, in such young girls, their bone growth occurs at the tips of the long bones where bone is soft and where few blood vessels penetrate this part of the bone. When young girls reach the age of menarche, their bone marrow turns from red bone marrow (making red cells) to a fatty bone marrow and this fat uses the aromatase enzyme to produce estrogen which cause the soft end of the bones to engage with a blood supply, thus ending bone growth. Among female ballet dancers in training, failure to reach the menarche due to excessively low body fat levels, allows the long bones to grow for longer which is why many great ballerinas have spider-like limbs, far longer than would be predicted by their height.

Fat is uniquely important in female biology. And yet, for the most part it remains a very poorly understood tissue. Perhaps a better understanding of the fat and fertility link might rehabilitate fat from simply embarrassing flab to a banner of femininity.

[1] For this blog I draw heavily on a book entitled “Female fertility and the body fat connection” (Chicago University Press) by Professor Rose Frisch, formerly of the Harvard School of Public Health who was a pioneer in this area

[2] In the early 18th century, the mean age of males undergoing voice change was 18 years in the choir of John Sebastian Bach. Today, it too has fallen to 13.5 years

Monday, February 13, 2012

Snakes, astronauts and consumer risk perception

In the Holy Trinity of Risk Analysis, that of Risk Communication is the Cinderella of the three while those of Risk Assessment and Risk Management are supreme. The reason why risk communication is so poorly serviced is that scientists and their supporting regulatory structures think that the mere provision of information to the consumer is all that is needed. The consumer is, apparently, worried for the wrong reason because he or she has simply got the facts wrong or confused. All that needs to be done is to educate them. That was how I thought about things until I read the work of Paul Slovik of the University or Oregon. Now, when teaching my students in this area, I tell them the following story. A group of rocket scientists are holding a meeting in a nice convention center. And just as a former astronaut of multiple space trips is about to speak, there is pandemonium as several snakes are discovered in the room, hissing and generally acting in a distinct anti-social manner. The rocket scientists pour out into the lobby led by the former astronaut. Next to their meeting is one of herpetologists, experts in snakes, and they note the concern of the rocket scientists. When they discover it is all due to some snakes in the room, they enter fearlessly and after a while they return smiling, if not tittering, to themselves and explain that these are “usually very harmless snakes and that they are most unlikely to cause any harm at this time of year and at this altitude, longitude and latitude. So, why not go back in and finish your meeting.” If I were there, I would tell the main man where to shove his snakes. Either we get a new snake-free room or it’s sayonara to this convention center. The snake expert is driven by logic while the rocket scientists are driven by emotion. The fears of consumers are emotional and no amount of scientific logic will readily dampen that emotional fear. Hence the mismatch between consumers and scientists.
Slovik points out that whereas “danger is real, risk is socially constructed”. We can start with US studies, which show that educated males trained in science and engineering have the highest threshold for risk. At first this was put down to their proximity to and familiarity with industrial risks and their background training. However, a study that compared male and female US toxicologists showed that females had a lower tolerance of risk. Thus the educational and familiarity aspects were no longer applicable. Men are from Mars and women from Venus. Vive la difference! This comparison was then taken further comparing US and EU male and female toxicologists. The same male-female difference was observed in the EU as had been seen in the US. However, both male and female toxicologists in the EU had a lower threshold of risk compared to their US counterparts. Risk is indeed, socially constructed.

Consumers also diverge from mainstream science in their vision of those aspects of risk that mark the greatest danger to them personally. Paul Slovik cites three main aspects of risk that are used by consumers in constructing a perceived danger to their health namely “dread”, “familiarity” and “control”. First let us look at a public health problem, which has an extremely low population impact but a huge personal impact on those who fall victims to the disease. Creutzfeldt-Jakob disease (CJD) is the human manifestation of “mad cow disease” (BSE) and leads to a dreadful death in humans. So we can tick off the first factor, “dread”. The idea that we develop holes in our brains and die a slow and agonising death is truly dreaded. Few of us know of anyone who suffered CJD or who had a close relative that encountered this disease and so it is utterly unfamiliar to us. The second box is ticked. And finally there is control. How can you know where BSE prions lie? You can’t so you really are at the mercy of lady luck which ticks box three “control”. Let us now compare this fear to that of obesity, which has enormous public health costs and which renders great suffering on large numbers of people. First it isn’t “dreaded”. Obese people can be fit, happy and highly successful and lead a long life! We do not dread obesity and we are also “familiar” with it. Indeed we all know obese people. And finally we can “control” it any time we like by going on a diet and taking up physical activity and we all know people who have lost weight. Thus the consumer sees the greatest danger in areas such as nanotechnology, GM foods, pesticides, additives, CJD, irradiated food and so on. These are dreaded, unfamiliar and out of the control of consumers. The facts that they pose little or no real population risk doesn’t matter. Obesity, sedentary lifestyle, high blood pressure and the like are not seen as something to dread or fear. To add further to this complexity, when consumers are asked about the risk of obesity to society as a whole versus themselves, they see a much higher risk for society as a whole compared to them personally since, irrespective of their weight, they can personally take control of the situation and avoid the problems of overweight and obesity. They of course cannot say the same for the rest of society. They can control themselves whenever they choose to do so, even if society in general cannot.

Slovik makes a critically important point: “Danger is real but risk is socially constructed. Thus, whoever controls the definition of risk controls the rational solution to the problem at hand. Defining risk is thus an exercise in power”. Eco-fundamentalist NGOs are the main definers of risk and they answer to nobody. They are the darlings of the media and the Robin Hoods of the consumers.  Their opposition to a new technology is usually based on some philosophical, moral or social stance. However, they communicate these concerns to the consumer, not by arguing the moral, philosophical or social case but by scaring them with distortions of the scientific facts. The road is risk communication is a long and complex road and it is a road that generally attracts little serious interest in the governmental task of risk analysis.

Monday, February 6, 2012

Your gut is inside out

Recently, I had dinner with my granddaughter Bella (11+) in our favourite restaurant and in the course of the conversation I asked her if she thought her gut was inside her or outside her. She gave me that “Grand Dad, stop being foolish” look. I then challenged with the fact that when we were children, her Uncle Fintan swallowed a threepenny bit (detour to explain) and that when our mother recovered it from his stool, it was in mint condition after a quick wash. “If it was inside him, how come it came out again” I asked only to be given that same look. Out gut is not inside us. It is simply a hollow tube from mouth to anus and in order to get “inside” us you have to cross the gut wall. Grand Dad’s are not always wrong.

Among the organs of the body, the gut is the least loved. It is always associated with the privacy of toilets and from time to time the terrors of food poisoning with trouble at both ends. In fact the gut is not only a very complex organ but it is a very intelligent organ. Not long after conception, a neural crest is formed which will eventually form the human brain. However, it splits and most of the crest goes to the brain while the rest forms the amazing nervous system of the gut. The two are then connected by the vagus nerve. There is more nervous tissue in the gut than in the spinal cord, which carries all the nervous material from the brain to all the organs of the body.  If you think about it, you experience your “gut brain” regularly. Think of the phrases we use: “He hadn’t the guts for it” or “I had butterflies in my tummy” or “I had a gut feeling”. All these phrases point to our awareness of the gut in times of stress. The gut consumes a large amount of the blood flow of the body and when there is trouble ahead, this blood flow falls to enable greater flow to the brain. When the trouble requires us to flee, we may do so having either suddenly emptied our bowels either end, or we flee with no further toilet stops.  There is another reason why our gut needs a brain, which is localised. If we encounter a deadly poison from some bacteria in our gut, it pays to get rid of it very rapidly. Any delay in connecting the toxin to the systemic immune system might just be long enough for permanent damage to be done. Thus the gut induces either vomiting or diarrhea to expel the toxin.

A second major feature of our gut is the colonisation of the gut, particularly the large bowel, with bacteria. Once upon a time, these bacteria were seen as no more than a bioprocessing unit, breaking down the fibrous components of our diet which our digestive enzymes cannot handle. Now we know that these bacteria play a major role in many aspects of our metabolism and our immune system. The human body is warm and moist and thus it attracts bacteria on all outer surfaces most notably the skin and the gut. The latter is not only warm and moist but it is also laden with nutrients. It pays, therefore, for man to have evolved a mutual relationship with favourable forms of bacteria in return for housing them in our gut. In effect, we have a peace treaty with our gut microbes: They keep away pathogens and we house and feed them. There is now very considerable interest in the role our gut microflora play in our everyday health. Their range of genetic material is 100 times greater than ours and some of these genes directly influence our genes in directing metabolism. Their role in obesity is attracting very considerable interest

It is possible to raise mice that have no colonic bacteria, referred to as germ-free. Experiments with conventional and germ-free mice fed an identical high fat diet, show that whereas the conventional animals will get fat, the germ free animals resist this trend and remain lean. These researchers went one step further and looked at a protein found in blood called Fasting-Induced Adipocyte Factor (FIAF). The cells of our gut wall can produce this protein but our normal gut bacteria suppress its manufacture: one of many examples of their genome telling our genome what to do! FIAF blocks the uptake of fats from blood into our adipose tissue stores. By slowing down FIAF release from the gut, the bacteria are now allowing fat to move from blood into adipose tissue. In germ-free animals, there is no such suppression and FIAF blocks the uptake of fat into adipose tissue. To test the link between germ free animals and obesity, the team then genetically engineered these mice to block FIAF synthesis. The germ-free mice now got fat. Thus, in addition to making a good bioreactor for the extraction of maximum calories from food, the gut microbes keep a check on FIAF allowing fat to move from blood into adipose tissue. That our gut bacteria talk to our adipose tissue via FIAF might wake us up to pay more attention to their welfare.