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!

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

[2] http://en.wikipedia.org/wiki/BRICS

[3] http://scalingupnutrition.org

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.

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[1] Suzuki et al (2013) AJCN 97, 1004013

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

Vitamin D ~ Down but not out

Vitamin D remains a vitamin of great interest at present with opinions favouring and opposing its role in obesity and the associated morbidity of obesity, the metabolic syndrome, specifically, the glycaemic side of the metabolic syndrome. One recent paper has used a rather clever approach to ascertain the role of vitamin D in obesity[1]. They used data from 21 adult cohorts amounting to over 42,000 subjects for whom data was available on body weight (body mass index) and for whom detailed data on various aspects of gene sequence was also available.  The authors selected 12 genetic variations (single nucleotide polymorphisms) linked to obesity. Based on a previous meta-analysis of the observed effect of each genetic variation on BMI, the authors assigned a score of 0, 1 or 2 to each BMI related gene variant where 2 was a high degree of association with 0 at the lower end of the gene-BMI association. Each subject was thus assigned a score with a maximum of 24 and a minimum of zero. As the BMI gene score increased, so too did BMI. And as it did, the levels of plasma vitamin D fell. Thus for each unit rise in BMI, there was a 1.2% fall in plasma vitamin D. This tells us that as BMI rises, plasma vitamin D falls, a trend that has been observed before. But is it that low levels of vitamin D in blood lead to obesity or is it that high levels of obesity lead to lower plasma vitamin D levels. The latter is of course an attractive hypothesis since vitamin D is a fat-soluble vitamin and it remains possible that this vitamin moves out of plasma into the fatty environment of adipose tissue. To answer that question, the researchers also looked at two forms of genetic variation in vitamin D metabolism – an assortment of genetic variants, which drive vitamin D synthesis and another group, which drive vitamin D breakdown. Based on the mix of inherited genes, vitamin D levels varied but this variation showed absolutely no association with obesity. Together, these data show that the lower levels of vitamin D found in obesity are due solely to the dilution of plasma vitamin D with the migration of significant quantities from blood to adipose tissue.

Obesity is however, a very crude measure of phenotype and it is associated with many metabolic abnormalities, one of which is insulin sensitivity. Inadequate blood levels of vitamin D have been linked to disorders of glucose metabolism including impaired insulin sensitivity. Thus a recent study investigated the effects of supplementing the diets of adolescents with plasma vitamin D on a wide variety of glucose metabolic aspects of metabolism[2].  A group of 18 obese adolescents were given vitamin d for 6 months while a second group of 17 subjects received a placebo. Plasma vitamin D levels {25(OH)} doubled in the treatment group and remained unchanged in the placebo group. No effects were observed on BMI although the group as a whole was severely obese (39kg/m²). A highly significant improvement in insulin sensitivity was found for the vitamin D group but not the placebo group using two reliable methods of measuring (HOMA-IR and QUICKI). Fasting plasma glucose was not altered by vitamin D supplementation although fasting plasma insulin levels showed a significant reduction with vitamin D treatment. Thus a lower level of insulin managed to maintain comparable levels of blood glucose indicating an enhanced efficiency of the function of plasma insulin. Two key hormones associated with energy metabolism leptin and adiponectin did show a change in their ratio (leptin to adiponectin) and the greater the response observed to vitamin D supplementation, the greater was the change in in this ratio.

Clearly, vitamin D is not directly linked to obesity but it continues to display a role in the area of enhanced insulin secretion, enhanced insulin function and improved overall glucose metabolism. The present study would suggest that vitamin D supplementation might be a useful adjunct to standard metabolic management of severe obesity but the results of the present study would need to be replicated and with a larger sample size.

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[1] Vimaleswaran KS et al (2013) PLoS Medicine, 10(2), e1001383

[2] Belenchia MA et al (2013) Am J Clin Nutr 97, 774-781

Google Authors Talk on my book

Google Authors Talk

http://www.youtube.com/watch?v=Ktmi-HCDosc&list=UUbmNph6atAoGfqLoCL_duAg&index=1

Todays blog is a video of a talk I gave on my book as part of the Google Authors series

Nutritional epidemiology ~ Faith or facts

In the course of a recent lecture on the subject of obesity, an issue arose in the discussion about an incremental approach to solutions for obesity. Thus individual action plans might seem very modest but a suite of such action plans could be successful in treating obesity. Allied to this viewpoint about incremental solutions came the old chestnut that sometimes, in epidemiology, we need to take action even if we don’t have definitive proof of the efficacy of that action. This chestnut, hankers back to the founder of modern day epidemiology, John Snow, who disconnected the tap from the water pump in Broad Street London, thereby ending a cholera outbreak. It is argued that Snow did not have definitive proof and this is the root of the view that sometimes, epidemiology needs to take a leap of faith. However, as Snow himself points out, of the 71 deaths he investigated, 61 were of people living in the vicinity of Broad Street and thus users of the pump. Three deaths occurred in children who lived nearer another pump but who went to school close to the Broad Street pump. Five others “preferred” the water at Broad street over their local pump. Only two deaths could not be linked to the guilty pump. All of this happened prior to our understanding of pathogenic microorganisms so Snow clearly couldn’t have used culture techniques to verify the organisms presence. He could have asked persons living away from the pump in question to drink the water in question but even in Snow’s time, the unwritten ethical position was: “First do no harm”. And so, armed with a dot map and his 71 case histories, the pump was disabled. This may have been a leap of faith in that definitive proof of cause and effect wasn’t to hand, but the quality of Snow’s data was excellent and compelling.

So in the field of human nutrition, how much of our public health nutrition policy is based on fact and how much on faith. In the early 1950’s. Ancel Keys studies the relationship between dietary fats, plasma cholesterol and the rate of heart disease in seven countries across the globe. Keys and his colleague Paco Grande then completed a series of human intervention studies in which patients in a psychiatric hospital were fen on reconstituted milk with a wide variety of fats and oils. The net outcome was definitive proof that the effects of dietary fat on plasma cholesterol could be accurately predicted using equations derived in their studies. But was there proof that lowering cholesterol would reduce the risk of heart disease. Endless studies ensued and all showed that high levels of plasma cholesterol were , at a population level, predictive of a higher risk of heart disease. Thus the dietary lipid hypothesis was upheld and entered the policy arena of public health nutrition.

A contrasting story is that of antioxidant micronutrients, particularly vitamins C and E. In the early 1980s, there was a widespread belief that plasma antioxidant levels played a major role in cardiovascular disease, in cancer and in ageing. The data was dominated by associations studies linking published levels of plasma antioxidant status in different countries with national disease rates. The relationships were most impressive. Animal studies also added to the theory and in vitro studies abounded showing how anti-oxidant vitamins could protect fractions such as low-density lipoprotein from oxidative damage which would otherwise render them very atherogenic. As often happens in the field of health research, someone wanted to cut to the chase and head for glory with a human intervention study. And so the ATBC (alpha tocopherol {vitamin E} beta carotene) study was designed and implemented. It failed to uphold the hypothesis and many reasons were put forward as to why the study was “unsuccessful”. Based on knowledge of these flaws, more intervention studies were rushed along and, all in all, the antioxidant theory was abandoned.

We can look at some other “successes” and “failures” in nutritional epidemiology. The protective role of folic acid in reducing the risk of a neural tube defect birth was shown in a randomized controlled trial leading to a major initiative in public health nutrition with the fortification of flour with folic acid. Trans fatty acids were removed from the food chain wherever possible on the basis of a strong human intervention study. In contrast, notwithstanding the strong evidence from correlational studies in humans of a link between fish oil fatty acids and cognitive decline, endless intervention studies have failed to show a protective effect.

Thus we have an excellent track record in human nutrition in translating observational studies that show an association between some aspect of diet and some health attribute into dietary intervention studies and then basing our policy interventions on food of those intervention studies.

Taxing sugar-sweetened beverages to reduce the incidence of obesity requires data from human intervention studies that show a direct link between weight gain and consumption of such beverages at rates that correspond to reality before anything is done. There are intervention studies and meta-analyses of such studies and the evidence is very weak if non-existent. To suggest that we trust these data so much and that we are fully confident that fiscal measures will be always positive and rarely negative is simply wrong and is bad science. To argue that sometimes we need to take leaps of faith in nutrition policy flies in the face of 6 decades of rigorous research on which nutrition policy has been built. Facts and not faith should drive policy. Facts are universal but faith is a subjective value.