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Sunday, June 30, 2013

Fat spat: Scientists argue over obesity risks

I have long argued that dissent is the oxygen of science and that whereas unanimity of opinion is fine for political parties and religious organisations, it has no place in science. Indeed, I have always held the view that the unexpected finding in science is its jewel. It is not a view that is widely held since science tends to be protective of its theories and dislikes having its conventional wisdom challenged. Right now, a major row has broken out over the true health risks of being moderately overweight. There are two dimensions to this squabble, the scientific dimension and the policy dimension. Let’s start with the science.

Katherine Flegal is a scientist at the US National Center for Health Statistics and she specialises in the study of the obesity epidemic in the US. In January of this year, Flegal and her colleagues published a paper in the Journal of The American Medical Association[1] in which she showed that persons who were overweight but not obese, had a statistically lower chance of dying than persons with a bodyweight deemed to be within the normal range. Her paper was based on a systematic review of the scientific literature on obesity in which she searched the literature for any study that involved the use of standardised classes of body weight (body mass index: BMI) and which involved a follow up period from baseline measures that allowed for an estimate of the relative risk of mortality across different standardised classes of BMI. She included all languages in her search and also excluded studies that failed to use the standard BMI classes, involved adolescents or which involved subjects with specific medical conditions. In all, she included 97 studies, which involved 2.88 million people with a total number of deaths in follow-up of 270,000. The papers were selected initially by Flegal but were included in the analysis only with the unanimous agreement of three independent reviewers. Top science here!

Her findings that overweight people had a 6% lower risk of mortality than normal weight individuals wasn’t new but it was a massively comprehensive study compared to all previous studies, which had shown this effect. The Journal commissioned a guest editorial on the paper from Dr Steven Heymsfield, Director of the Pennington Institute in Baton Rouge, a center of excellence in obesity research[2].  This editorial notes that: “Body Mass Index is an imperfect predictor of metabolic risk” and concludes by stating that: “Establishing BMI is only the first step toward a more comprehensive risk evaluation”. So, let’s pause here. We have one of America’s leading statisticians on the obesity epidemic publishing the most comprehensive paper of its kind in this field in a top academic journal following the normal rigors of peer review and we have a very supportive guest editorial by the director of the leading obesity research centre in the US.

However, the dons at the Harvard School of Public Health were not happy. Led by Professor Walter Willett, they held a special meeting to line up critics of the Flegal paper. In a radio interview[3], Willet stated: “This study is really a pile of rubbish and no one should waste their time reading it”. This in turn led to an editorial in Nature[4] and an overview article entitled “The big fat truth” by science journalist Virginia Hughes.[5]  She reviews some literature and draws on data, which shows that the relationship between BMI and mortality varies greatly with age. In older people, at the lower and at the upper spectrum of BMI, the risk of mortality is higher than it is for the majority of the population who are neither too skinny nor too fat. In younger people, the lower low BMI values are not associated with elevated risk.

Leaving the science aside, there is a critically important aspect to this row that needs highlighting. Think back to the BSE crisis. At that point, within the EU we had the risk assessment process and the risk management process both operated by the European Commission. That was then amended to take the risk assessment process away from the Commission and to create a totally science- based independent body, The European Food Safety Authority, to conduct risk assessment. The Harvard group is effectively seeking to be both risk assessors and risk managers. The former is science based and the latter is politically or policy based. If the two are attended to within the same institute, as the Harvard group seem to want, then the risk management process will filter the risk assessment process. Why support a scientific paper, which conflicts with your risk management goals? Indeed, in this week’s Harvard Gazette which covered this controversy, Professor Willett is quoted thus: “If you don’t have the right goal you are very unlikely to end up in the right place”[6]. Clearly, Professor Willett knows what is “right” and those who differ are “wrong”. This is simply bad for science. As I said, dissent is the oxygen of science.

[1] Flegal KM et al (2013) JAMA, 309 (1) 71-82
[2] Hyemsfield SB (2013) JAMA, 309, 87-88
[4] “Shades of grey” Nature (2013), 497, 410
[5] “The big fat truth” Hughes V (2013) Nature 497, 428-430

Sunday, June 23, 2013

Economics and infant malnutrition

At the recent G8 Summit on the shores of Lough Erne here in Ireland, a new declaration was signed to chase the big multi nationals for a fairer share of their sales to be paid as tax. Google generated  £11.5bn in profits in the UK and only paid £10m in tax during that period. In the UK in 2011, Apple Sales International generated UK sales valued at $22bn but paid only $10m in tax. In the week before the G8 summit the NGO Save the Children issue an in-depth report also looking at global economic development but with a focus on malnutrition[1].  The main conclusion of this report is that if today’s infants are not properly nourished, the global economic loss in 2030, when these infants reach working age, will be $125 billion.

The first part of this report deals with what is called the “demographic dividend” which is characterised by an increase in the ratio of the population available for work versus the those who cant work because they are too young or too old. It is expected that due to rapidly falling mortality rates and declining fertility rates, many poor countries will have two persons at work-force age for every one person too old or too young to work. Indeed, the IMF have predicted that seven of the ten fastest growing economies in the next five years will be in Africa. Rapidly growing economies require a work force that is physically capable of hard work and a work force, which has achieved its optimal cognitive function. Therein lies the power of adequate nutrition in the first 1000 days.

This first 1000 days refers to the 9 months (36 weeks) of pregnancy plus the first 2 years (104 weeks) of infancy (140*7=980 days). If a child emerges from this period with impaired cognitive and physical potential, the effect is life-long. Iron, for example, is essential for muscle growth but also for the fat sheath (myelin)  that surrounds the nerve cells in the human brain and for the synthesis of the signals (neurotransmitters) that travel from one neuron to the other. Longitudinal studies consistently show that infant anaemia is associated with long-term decline in cognitive capacity, with learning difficulties and ultimately with behavioural disorders. At present, the World Health Organisation estimates that in middle and low-income countries, 47% of infants are anaemic. Iodine is also a major micronutrient deficiency issue and presently some 2 billion people (one third of mankind) have inadequate iodine intake, a third of which are children. Once again, iodine is involved in physical activity since it is an integral part of the thyroid hormone, which not only regulates energy metabolism in the body but also serves to optimise brain development, particularly during pregnancy. One could go on to mention zinc, folic acid, vitamin B12 or omega 3 fats. The bottom line is that poor nutrition during pregnancy and in infancy will lead to permanent loss of physical and mental capacity. Thus if the demographic dividend is to pay off, the present population of mothers and infants must have optimal nutrition for gestation, through 6 months of exclusive breast feeding and through safe and wholesome weaning.

Some 27 years ago I wrote a popular book on nutrition and in it I cited an author who wrote thus of the malnourished: “The light of curiosity absent from children’s eye. Twelve year olds with the physical stature of eight year olds. Youngsters who lack the energy to brush aside the flies about the sores on their faces.  Agonizingly slow reflexes of adults crossing traffic. Thirty year old mothers who look sixty. All are common images in developing countries; all reflect inadequate nutrition; all have societal consequences”. Not a lot has changed except that now we recognise that the focus must be on maternal and infant nutrition. If we get that right, economic growth is possible with the demographic dividend. If we don’t we’ll have very large numbers of unemployed or under-employed young males, a recipe for conflict and social setbacks.

So, returning to the economics of mother and infant malnutrition, the report shows that a 1% increase in height equates to a 2.4% increase in earnings. Infants who were well nourished during the first 1000 days grew up to work on average, 5 hours longer per week than children who had poor nutrition during this period and, in addition, the well nourished infants grew up to earn 20% more per hour than poorly nourished children. In India, the economic cost of childhood malnutrition is estimated at between 0.8 and 2.5% of GDP equivalent to $15-46 billion. In China, another BRICS country[2], the comparable cost of micronutrient deficiency is $15-29 billion.

The UN initiative Scaling Up Nutrition (SUN)[3] is a major international programme to which some 40 countries have signed up to which specifically seeks to address the problem of infant and maternal nutrition and which specifically recognises the economic necessity of proper nutrition in the first 1,000 days. The prospect of 7 of the 10 fastest growing global economies being based in Africa is truly exciting. Google and Apple: pay up please!

[1] (Food for thought: tackling child malnutrition to unlock potential and boost prosperity)

Sunday, June 16, 2013

Vitamin D and Parkinson's Disease

The following is a direct quote from the Mayo Clinic’s website on Parkinson’s disease: “Parkinson's disease is a progressive disorder of the nervous system that affects your movement. It develops gradually, sometimes starting with a barely noticeable tremor in just one hand. But while tremor may be the most well known sign of Parkinson's disease, the disorder also commonly causes stiffness or slowing of movement. In early stages of Parkinson's disease, your face may show little or no expression, or your arms may not swing when you walk. Your speech may become soft or slurred. Parkinson's disease symptoms worsen as your condition progresses over time. Although Parkinson's disease can't be cured, medications may markedly improve your symptoms. In occasional cases, your doctor may suggest surgery to regulate certain regions of your brain and improve your symptoms”.

A recent paper in the American Journal of Clinical Nutrition[1] looked at the role of vitamin D in Parkinson’s disease (PD).  The authors, from the Jikei University Medical School in Tokyo, present at the outset a summary of the existing data. Those who suffer from PD have lower blood levels of vitamin D. They also have lower bone mineral density and a higher risk of falls. In the US, there is a North-South gradient in the incidence of PD, which may reflect a North-South gradient in sunshine bearing in mind that vitamin D is the sunshine vitamin. They also point out that the enzymes responsible for the synthesis of the active form of blood vitamin D are expressed in highest concentration in that part of the brain where there is most neuronal damage in PD (substantia nigra).  Finally, they point out that in mice, where the vitamin D receptor, which transports vitamin D into cells is deleted using genetic knock out technology, show characteristics of PD.

All of this, while interesting, is entirely correlational in nature and does not prove cause and effect. The authors therefore set out to test the hypothesis that vitamin D is directly related to PD by conducting a randomized, double blind placebo controlled study. Patients with PD were randomly assigned to receive either a placebo or a vitamin D supplement for 12 months. Neither the patients nor the investigating physicians knew which was which since this was a blinded study. The patients were followed every 2 to 12 weeks and were clinically examined to ascertain the progression or otherwise of their condition using the Hoehn and Yahr (HY) scaling system. The average age of the patients was 72 years.

Compared to those given the placebo, those given the vitamin D supplement showed a highly statistically significant slowing down of the rate of progression of PD. No adverse effects were observed. The authors rightly take a conservative view of these results, They point out that in this age group, vitamin D supplementation generally improves muscle strength and overall balance and the extent to which the improvement in PD symptoms might be influenced by this non-specific effect is unknown. The authors also included a genetic component to their studies. They showed that those PD patients with a particular genetic variation of the vitamin D receptor (FokI T allele) responded best. A related editorial in this edition of the AJCN[2], researchers from The Queensland Brain Institute also adds to the general argument that vitamin D has a neuroprotective role. Supporting the arguments of the authors of the intervention study, they add that vitamin D supplementation reduces the side effects of some drugs used in the therapy of PD. They also go on to argue that if the findings of the intervention study are replicated and if no adverse effects are seen then “there is a case to translate this treatment promptly. Even if optimal vitamin D status delays PD progression by a small degree, this treatment is cheap, simple to access, relatively safe and publicly acceptable”.

This is yet another example of a study which flies in the face of the high priests of dietetics who constantly argue that a health diet will provide all of an individual’s nutrient requirements. It also highlights the need to marry an individual’s genetic make-up to their response to a nutritional intervention. Regrettably, the ruthless supplement industry will exploit this paper and make absurdly exaggerated claims about vitamins.

[1] Suzuki et al (2013) AJCN 97, 1004013
[2] Cui et al (2013) AJCN, 97, 907-908