Oh Sugar! Wrong about fructose

Of late, the words “toxic”, “sugar” and “fructose” have been widely used together, implying a most dangerous aspect of sugar on human metabolism. The irony is that in Greek mythology, Cronus, the Titan leader was fed so much honey that he fell into a deep sleep during which time his son Zeus killed him. The original words of the Greek legend refer to the “intoxicating effect” of the large intake of honey on Cronus. Just as we are amused but not troubled by the language or beliefs of Greek mythology, we should not be so troubled by the same nonsense reformulated in modern Californian mythology.  Honey was always held as a truly prized food: hard to harvest, made by bees through some mysterious process foreign to all other plant and animal foods, golden in colour and above all, sweet as nothing else ever known to man. The sweetness of honey was down to a combination of two simple sugars, fructose and glucose present at 55% and 45% respectively. Sugar, as we know it today, is also an ancient food but newer, relatively speaking, than honey. It is plant-derived and the very first commercial facility for the extraction of sugar in crystalline form from sugar cane or sugar beet was located on the Island of Crete.  The Arabian merchants who funded this production facility had another name for Crete, which they called Qandi. Hence the term “candy”, used today mainly in the US for sugar confectionary products. The main component of this sugar derived from cane or beet is the sugar “sucrose” which is a couplet of two sugars joined together, fructose and glucose.

Honey and particularly sugar, dominated the sweetness aspect of the human diet. That was to change in the 1980’s with the advent of high fructose corn syrup (HFCS) production, driven by simple economics. In the period up to the early 1980’s, US and global sugar prices were pretty identical and highly subject to wild fluctuations in market supply. Thus, in 1974 and 1979-1980, US and global sugar prices soared 5 fold in two separate market peaks. The advent of a new technology that could replace sugar with an identical alternative at a stable low price became a simple no-brainer. Sugar was priced out of the US markets with strict import quotas introduced in the early 1980s to maintain very high domestic sugar prices, double the global price.  HFCS was to almost completely replace sugar in the US diet. The manufacture of HFCS is technically simple. Starch, which is a polymer of glucose units, is extracted from corn and enzymes are used to first break down the starch to glucose. Half the glucose is converted to fructose, again using a simple enzyme system.  The glucose and fructose can now be blended together and the most popular blend with consumers was 55% fructose and 45% glucose, an identical blend to that found in honey.  HFCS intakes soared 8-fold in the US from 1975 to the 80s-90s. However, in recent years HFCS intake has fallen in the US and is now back to values in 1980. During the surge in the use of HFCS, that of sugar fell pro rata.

In 2004, some leading US obesity researchers published data to show that the epidemic of obesity in the US coincided with the surge in HFCS use in the food chain. Whilst most scientific commentators have dismissed this putative link, the debate rages on with thousands of doom-laden Internet postings fuelled by a handful of media-friendly scientists. The term “high fructose corn syrup” was in hindsight a foolish name to introduce since HFCS is quite simply not high in fructose, equal in fact to the level found in honey and almost equal to the level found in sugar. Fructose is the element of HFCS that has been singled out as the bad part and the research in this area leaves a lot to be desired. To begin with, humans don’t and never have consumed fructose in isolation. It is always consumed with glucose and thus experiments in humans or animals using diets with high fructose levels with no accompanying glucose are basically unrealistic. They may show what is possible but they have no bearing on what is probable. In a paper presented to the US Experimental Biology conference in 2012[1], the levels of fructose used in these diets was compared to the average daily intake of fructose by US adults. In every one of the 37 human studies and every one of the 21 animal studies, the level of fructose used exceeded the US average intake value (9% of calories). Of course the average hides high consumers so this paper also looked at the fructose intake of the top 5% of fructose consumption (15% of calories). Only 3 human and 1 animal study were at or below this very high level of intake. The majority of animal studies used as much as 55% of calories from fructose, a situation, which is impossible to envisage in the human diet except maybe in the make-believe land of milk and honey.

None of these studies needed to be funded since a natural experiment was being acted out on both sides of the Atlantic. Just as the US jacked up sugar prices to promote HFCS usage, in the EU sugar beet farmers were protected under the CAP limiting the use of HFCS to 5% of total supply. Thus beverages in the US contain HFCS whilst beverages in the EU do not. Nonetheless, obesity levels have grown dramatically either side of the ocean.  While the debate on HFCS rages on the Internet, two key organisations have pinned their colours to the mast. Both the American Medical Association[2] and the American Dietetic Association[3] have issued position statements dismissing any claim that HFCS use contributes to obesity or associated biochemical abnormalities of blood lipids or blood glucose.

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[1] White JS (2013) Adv Nutr, 4, 246-256

[2] http://www.ama-assn.org/resources/doc/csaph/csaph3a08-summary.pdf

[3] Journal of the American Dietetic Association, (2004) 104, 255-275

Nutrition in the first 1,000 days: How strong is the data?

The first 1,000 days represents the development of a child from conception through to 2 years of age. Maternal and infant nutrition during this period has become the corner stone of many international programmes to combat malnutrition. The message relayed within this area is simple: Optimal height for age and optimal cognitive function are largely determined during the first 1,000 days. If a child suffers poor nutrition during this period, then there is permanent reduction in stature and a permanent loss of cognitive function. The UN initiative “Scaling Up Nutrition” (SUN) which has now been adopted by 45 countries has the first 1,000 days and maternal-infant nutrition as its core. However, a recent review and analysis published in the American Journal of Clinical Nutrition and led by Andrew Prentice of the London School of Hygiene and Tropical Medicine[1], would certainly demand a more rigorous review of a policy which effectively espouses the view that the first 1,000 days is the make-or-break period for physical development.

The paper begins by describing the data upon which the first 1,000 days theory is based. These data show that in 54 countries with low incomes, children are born with heights below the WHO growth standards and that this height deficit deteriorates over the first 2 years of life and then remains stable for the remainder of the study, which lasted 5 years. The authors point out that these data come from an “amalgamation of large-scale nationally representative data sets that were not collected for research purposes”.  They also point out that the original data from Africa does show some, albeit modest recovery in height between 24 and 48 months.

The second point made by the authors is that whereas most brain and neuronal development takes place in the first 1,000 days, most other tissues show significant growth after this period, all of which are driven by hormonal development, differing for males and females. The peak growth of lymphoid tissue occurs between 5 and 10 years of age while muscles, bones and reproductive organs show a surge in growth in the early to mid teens. If different organs grow at different rates at different ages, then it is logical to assume that sub-optimal nutrition can modify this growth well outside the first 1,000 days. The authors present data from Brazil, Guatemala, The Philippines and South Africa, which clearly shows recovery in height after the first 1,000 days and that this recovery is not based on any special nutrition intervention. India is exceptional in not showing any post 2-year height recovery. The research base of Andrew Prentice is in rural Gambia and over 6 decades, the growth of children from local subsistence farming villages has been recorded. The data show the expected fall in height in the first 1,000 days of these poor children. However, it shows very good recovery thereafter. Then as growth demands are increased in puberty, there is a temporary fall in height for age, which again shows recovery and plateaus in the second decade of life.  All of these data challenge the concept that the first 1,000 days is the only critical period of growth and that interventions outside that period are unlikely to have any effect.

The authors now move on to look at the actual evidence of the effects of nutritional intervention during pregnancy and early childhood. As regards pregnancy, the authors cite the Cochrane Review of 23 protein-energy supplement trials reached the following conclusion[2]: “Dietary advice appears effective in increasing pregnant women's energy and protein intakes but is unlikely to confer major benefits on infant or maternal health. Balanced energy/protein supplementation improves fetal growth and may reduce the risk of fetal and neonatal death. High-protein or balanced protein supplementation alone is not beneficial and may be harmful to the infant. Protein/energy restriction of pregnant women who are overweight or exhibit high weight gain is unlikely to be beneficial and may be harmful to the infant.” The authors also cite meta-analyses of pre-natal trials involving 17 with zinc supplementation and 49 with iron and folic acid supplementation. The outcome of the meta-analyses was that these nutritional supplements produced non-significant effects on birth outcome. As the authors point out, these trials cannot be dismissed and furthermore cannot be considered to be flawed by design. They then cite a meta-analysis of 42 trials, which involved nutritional intervention in childhood involving complimentary feeding. Whereas some benefits were seen such as reduced rates of anaemia and improved micronutrient status, the authors argue “ in the context of the current discussion their analysis underscores the fact that the range of interventions before 24 months reported to date could only make a limited contribution to reducing stunting in poor populations”. Disappointing as they may be, again these studies cannot be dismissed. It may well be, as the authors argue, that a combination of poor hygiene, infection and infestation may negate any nutritional impact and they point out that trials combining both dietary and hygiene interventions are underway.

This is a very important paper and one that will trouble the first 1000-day proponents. It is also a very thoughtful paper because it emphasizes that that the first 1,000 days remains a very important period for potential life long impacts on growth. However, it is a paper that challenges both the strength of evidence of the first 1000 days and the concept that other critical periods of growth are of lesser importance. The authors did not consider cognition as an outcome of the first 1,000-day nutritional intervention. However, they do cite 2 papers, which challenge the view that cognitive development is again, confined to the first 1,000 days.

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[1] Prentice AM et al (2013) AJCN, 97:911-918

[2] http://www.ncbi.nlm.nih.gov/pubmed/14583907

A festive blog: Happiness and health

Blog on happiness

This is a season in which we all wish one another happiness for both Christmas and for the New Year. It is a time for happiness. However, research into happiness does not confine itself to seasons or birthdays but looks at overall happiness with life and, in some cases, attempts to relate that sense of happiness to our health. For this blog, I draw on a paper published in the Journal of Happiness Studies and no, this is not a joke, such a journal does exist published by the Springer[1] company and edited by Prof Antonella Dell Fave from Milan. Today’s blog centres on a paper from the Erasmus University of Rotterdam entitled:  “Healthy happiness: effects of happiness on physical health and the consequences for preventative care[2]”.

The author begins by accepting the view that physical health can be influenced by positive and negative mental states although this does not suggest any role for positive mental health in prevention of serious illness such as cancer. In this review the author focuses on longevity as a correlate with happiness and then asks how happiness can be exploited as a concept in the promotion of good health. In this context, happiness is defined as “overall appreciation of one’s own life-as-a-whole” or in other words “how much one likes the life one lives”. Such definitions of happiness allow for an objective and universal measure of how happy people are.

The author starts with the World Database of Happiness,[3] which shows that a positive and statistically significant correlation exists between measures of happiness and physical health. Those for self-reported health are greater than those correlations of happiness and health ratings based on medical opinion. However, correlations cannot tell us anything about cause and effect and so the author surveyed the literature in this area. Four studies were identified where some base line measure of happiness was taken and then health status (medically determined or self-reported) studied many years later. In general, those results were inconclusive, which led the author to look at measures of happiness and longevity, an objective measure of overall health. The author recorded a total of 30 such studies, eleven of which were among people who were in bad health. Happiness and longevity among this group was not at all clear-cut, reinforcing the earlier point that the biological evolution of chronic diseases, such as cancer, cannot be abated by happiness. Some 19 studies focused on health and happiness in healthy individuals. The follow up periods ranged from 1 to 60 years with 5 covering 20 years or more.  In total, some 24 effects of happiness and health were studied of which 16 (67%) were statistically positive while in the remaining 8 cases, a positive effect was observed which failed to reach statistical significance. The authors conclude that the evidence clearly points to the fact that happiness “protects” against falling ill.

This blogger would ask whether there are any overlaps between gene profiles for longevity and gene profiles for happiness. And, “surprise, surprise”, happiness is very highly heritable based on a large study of identical and non-identical twins in Minnesota[4]. A basic question on wellbeing was administered to 1380 twin pairs living together and was then re-administered to the same twins some 10 years later, leading to the conclusion that up to 80% of the stable aspect of wellbeing is heritable. So is it that happiness increases longevity or is it that to have the “happiness” genes is also to have the “longevity” genes. At this point in time we don’t know.

Happiness can influence health in many ways. Thus, it is well known that negative mental states promote poorer immune responses, higher blood pressure and other adverse physiological effects. In contrast, happiness is more likely to cope with threatening information and thus less fearful of preventative activities such as health screening. Happier people are more likely to engage in sports and are also less likely to be fatalistic as regards health.

Epidemiology deals with populations and tells us how our health trajectory is determined by our many lifestyle choices. But which is more important, health alone or happiness? Here in Ireland and I assume elsewhere, there is understandably a huge value put on being healthy. But happiness must over-ride health and so many individuals suffering from life-threatening conditions daily exhibit magnificent happiness. This is beyond the metrics of epidemiology for whom the bottom line is disease orientated. And if we move beneath life- threatening conditions and consider the risk factors for disease, the big paymaster of epidemiology, can we be happy and fat, or a happy smoker or a happy hypercholesterolaemic? Of course it would be best to be happy and healthy beyond imagination – Californian healthy even.

But that’s not life. Happiness must enter the lexicon of those concerned with life, lifestyle and wellbeing. It is the highest level of human achievement. And it can even be topped by also making someone else happy.

Happy Christmas to all my readers

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[1] http://link.springer.com/journal/10902

[2] Veenhoven R, (2008) J Happiness Stud, 9, 449-469

[3] http://www1.eur.nl/fsw/happiness

 [4]Hamer DH (1996)  Nature Genetics 14, 125 - 126 (1996)

Swedish report on diet and physical activity revals very weak science

The Nobel Laureate (immunology) Sir Peter Medawar once said that “If politics is the art of the possible, then science is the art of the soluble” and there is no better way of solving a problem than breaking it down to ever smaller units and then building it up again. In cell biology, this is easy. Isolate an enzyme and study its characteristics in the test tube. Then see what happens when an intact cell is put through its paces. Lucky cell biologists! Studying free-living humans poses an entirely different challenge with the boundaries of investigation set by factors ranging from ethics to practicalities of modern day life. Notwithstanding these challenges, the study of how the human diet influences our health must proceed with the highest possible rigour. In certain areas we can claim tremendous success such as the role of nutrients in neural tube defects, in age-related blindness, in blood lipids, in blood pressure, in bone disease and the like. In obesity, we have let ourselves down badly and nothing highlights this more than a recent systematic review of the data on diet and obesity concluded by The Swedish Council on Health Technology Assessment. Founded in 1987, this Council[1] is an independent national authority, tasked by the government with assessing health care interventions based on ‘systematic literature reviews’ of published research.

Last week (November 27^th, 2013) they launched a report: “Diet among obese individuals”[2]. In this instance, the data refer to those who are clinically obese with a BMI greater than 30kg/m². The systematic review covered all dietary intervention studies and those observational studies that lasted at least 6 months. The review covered all known publications up to the end on May this year. The authors used the internationally accepted GRADE[3] system to rank the scientific quality of the data. Studies with inconsistent results or imprecise findings/objectives or confounded by non-controlled factors were excluded. The accepted studies were used to collectively yield a conclusion as to the strength of the evidence linking diet to the treatment of clinical obesity. The following ranking was used: ++++ for high quality evidence, +++0 for moderate quality, ++00 for low quality and +000 for very low quality evidence. The results are presented for a variety of nutritional comparisons and then for foods.

If the document is searched for all conclusions ranked at the highest level (++++), only three appear.  They are:

·      “There is strong scientific data to indicate a link with increasing coffee intake and a reduced risk of diabetes among obese individuals”

·      “There is strong scientific data available to indicate that initiating dietary intervention with a VLED (very low energy diet) regimen of 8–12 weeks can achieve greatly increased weight loss over up to 12 months for obese individuals, but after two years the effect of the regimen is marginal”

·      “There is strong scientific data available to indicate that physical activity as a supplement to dietary intervention with energy restriction has no significant supplementary value for weight reduction after 6 months for obese individuals”

It is remarkable that only three conclusions reach what would be regarded as strong evidence. The report is however large enough for all “activists”, scientists and non-scientists, to find their own gems in the findings. For example, the Internet is awash with claims that this report slams low fat diets and applauds low carbohydrate diets.  However, the report is quite specific about comparisons between moderate low carbohydrate diets and low-fat diets in the clinically obese: “There is moderately strong scientific data to indicate that advice on moderate low carbohydrate diets compared with advice on low fat diets for obese individuals has a more beneficial effect on weight at 6 months. At 12 months, the effect on weight is the same (+++0). There is inadequate data available to assess whether there is any difference between advice on the two diets with regard to weight at 24 months (+000)”.  Twist it how you like but the facts are we have no long-term evidence on which to base such important food and nutrition policies. The same conclusions ring through most of the fat-carbohydrate comparisons in the report.

It is also worth looking at some of the conclusions on foods. On “Sweet drinks” the following is one key conclusion: “There is limited scientific data available to indicate that reduction of sweet drinks is linked to weight loss and lower blood pressure among obese individuals (++00)”.  For “chips” the report finds: “There is no data available to assess any effect of potatoes or chips on body weight (no studies are available)”.  For “Fruit and Vegetables”, the comments are:

·      “There is limited scientific data to indicate that advice on increased intake of fruit and vegetables, compared with advice on reduced fat intake, leads to slightly less pronounced weight loss at 6 months among obese individuals (++00). There is inadequate data available to determine whether there is any difference in effect on waist size (+000). For a longer period (12 months or more), there is inadequate data available to determine whether advice on increased intake of fruit and vegetables has a beneficial effect on body weight or waist size (+000).

• “There is inadequate scientific data available to determine whether intake of fruit and vegetables demonstrates a link with future weight change among obese individuals”.

One must bear in mind that this study was focused on weight management in the clinically obese and that what is relevant to that sector may not be relevant to the prevention of obesity or the long-term treatment of moderate overweight. Nonetheless, this influential report will serve if nothing else to show that of the 43 conclusions as regards to the role of nutrients in the management of clinical obesity, only one single conclusion (Very Low Energy Diets) met the top ++++ GRADE rating. Of the 51 conclusions on foods and lifestyle, two met this standard (coffee and physical activity). How poor is that.

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[1] http://www.sbu.se/en/

[2] http://www.sbu.se/en/Published/Yellow/Diet-and-Obesity/

[3] Oxman et al (2004) BMJ 328; 1490-1494