Poor Nutrition and Chronic Disease

Presented here is the concluding section of a two-part report on the proceedings of a Symposium, held at the SCN’s 22nd Session in Washington, D.C. in June 1995, entitled ‘Nutrition in the Epidemiology and Prevention of Cardiovascular Disease, Diabetes Mellitus, and Obesity in Developing Countries’ - a theme some might find surprising given the overwhelming levels of hunger and malnutrition facing many developing countries, and given that these are traditionally thought to be diseases of affluence. Nevertheless, as Dr J Jervell, President of the International Diabetes Federation pointed out in his introductory presentation at the Symposium reproduced in Part I (SCN News No. 13, late 1995) ‘Non-communicable diseases are emerging, not only with the same strength as they have done in the industrial world, but perhaps even more strongly in the developing countries - especially those which are developing fast.’ Consider, also, the evidence presented here which appears to suggest that malnutrition actually plays some part in causing chronic disease, and the implications for developing countries come into clear focus. Two presentations are reproduced and discussed. The first, by Dr J J Hoet of Louvain University, Belgium is entitled ‘The Role of Fetal and Infant Growth and Nutrition in the Causality of Diabetes and Cardiovascular Disease in Later Life’. The second, and concluding presentation is by Dr G H Beaton and is entitled ‘Prevention and the Role of Nutrition’.

THE ROLE OF FETAL AND INFANT GROWTH AND NUTRITION IN THE CAUSALITY OF DIABETES AND CARDIOVASCULAR DISEASE IN LATER LIFE

Dr Joseph J. Hoet, Professor Emeritus of Medicine, Co-Director WHO Collaborating Center for the Development of the Biology of the Endocrine Pancreas, Faculty of Science, Louvain University, B. 1348 Louvain-la-Neuve, Belgium

Clinical and experimental evidence indicates that there may be a causal link between fetal and infant growth and diabetes [see box] (specifically type II, or non-insulin dependent diabetes (NIDDM)), cardiovascular disease, and possibly obesity in later life. One study has indicated that of infants who weighed less than 2.5 kg at birth, and less than 8 kg at age one, 26% had impaired glucose tolerance [see box ] and 17% were afflicted with diabetes when they reached the age of 64 years, and that they were almost twice as likely to die of heart disease before the age of 65 compared with those who weighed more than 4.0 kg at birth. Other data have indicated that young children, born in underprivileged areas where there is a high incidence of low birth weight, already have high cholesterol and blood sugar levels, abnormal insulin levels, and elevated blood pressure. Collectively, these findings and others suggest that metabolic and vascular abnormalities that lead to chronic illnesses (diabetes, hypertension, and cardiovascular disease) in later life may have their origins in utero and during infancy.

Maternal nutrition plays a major role in fetal development and in determining birthweight, which in turn may have long term health consequences for the infant leading to chronic illness in later life. Understanding the mechanisms by which programming of the foetus and infant occurs may therefore lead to a new understanding of the origin of chronic disease and have implications to the approach to primary prevention.

The results of our studies using rats have provided some insight as to how the suggested link between increased susceptibility to NIDDM and IGT in later life, and fetal and infant nutrition and growth might work. Several years ago it was indicated that during fetal life, the pancreatic beta cells [see box] needed certain amino acids in order to be able to multiply properly. Based on this finding, a simple experiment was carried out to explore the long-term consequences of fetal protein malnutrition on the biology of the pancreas and the outcome in terms of glucose tolerance in the offspring.

Pregnant rats were divided into two groups; an experimental group which were fed a low protein diet, and a control group (C) which were fed a normal protein diet. Both groups had equal energy intake. The offspring of these two groups were then raised until the adult age of 84 days. The experimental group was further divided into two groups; the first continued with a low protein diet throughout life (Low protein or LP group), and the second, or recovery (R), group were fed a diet adequate in protein from birth. The control (C) group continued with a normal diet throughout life [see Figure].

Diabetes is a disorder of metabolism and occurs when the body is not able to make use of glucose in the blood for growth and energy. For glucose to enter the cells and be utilized, the hormone insulin is required. Insulin is produced in the pancreas; specifically, in the beta cells of the Islets of Langerhans. Diabetes occurs either because the pancreas is not able to make enough insulin, or because the insulin that is available is not effective. There are three main types of diabetes: insulin dependent, or type I diabetes; non-insulin dependent, or type II diabetes; and gestational diabetes. Insulin dependent diabetes is an autoimmune disease in which the insulin producing beta cells in the pancreas are destroyed resulting in little or no insulin production. Non-insulin dependent diabetes usually develops in adults and is the most common form of diabetes, where insulin is produced, but the body cannot use the insulin effectively. Gestational diabetes develops during pregnancy and usually disappears after pregnancy. Impaired glucose tolerance (IGT) is a condition, less than diabetes, where blood glucose levels are higher than normal. People with IGT may not develop diabetes.

At birth, pups from the experimental group weighed less and had reduced levels i.e. of the amino acid taurine, compared with the control group. Furthermore, the structure and function of the pancreas in the experimental group was abnormal. For example, beta cell proliferation and Islet size [see box] were reduced, and certain insulin secretory mechanisms were at fault. On examination of the pancreas of the adult (84 day old) offspring, secretory differences in vitro between the LP, R, and C groups were found which indicated that alterations observed at birth do remain when a low-protein diet is given until adulthood, and that a normal diet given immediately after birth only partially restores the normal pattern insulin secretion in vivo.

Glucose tolerance in each of the three groups of adult rats showed a gender difference. In the LP group, an abnormal low insulin secretion was observed in males and females. However, in the R group, normal glucose tolerance, with a satisfactory insulin response, was observed in males, whereas lower than normal insulin levels were found in females. It appeared, therefore, that for insulin secretion and glucose tolerance, the male animals were able to recuperate with a normal diet after birth, where as the female animals were not able to normalize their insulin secretion.

In the final part of the experiment, female rats in each of the first generation groups were submitted to pregnancy. During pregnancy the diets of the rats continued as they had during maturation. Results showed that the second generation offspring of the LP and R groups exhibited again structural and functional pancreatic abnormalities consistent with the presence of gestational metabolic alterations in their mothers. This meant that even in the recovery (R) group, where adequate protein was being provided through the mother dam but not to the grandmother, the fetal pancreas was developing in specific ways without achieving normal development.

In addition, we observed major deficits in blood vessel densities in the endocrine pancreas and the brain in the low protein (LP) group. With a normal diet postnatally (group R) they were normalized in the endocrine pancreas but not in the brain which kept a deficit of 30%. Therefore blood vessels such as of the brain were altered without rehabilitation capacity. Duodenal and renal vascularization was normal.

Moreover an isocaloric tow protein diet during gestation and a normal diet postnatally induces pathological changes in the liver, leading to a high glucose output at adulthood, as indicated by Professor C.N. Hales from Cambridge. Glomeruli maturation in the kidney is also delayed without recuperation at adulthood even with a normal diet postnatally as shown by several investigators. Thus the lack of adequate protein availability during gestation induces developmental disabilities with consequences in adulthood in organs responsible for diabetes and causal for vascular disease and hypertension.

Diabetes is widespread throughout the world, affecting all kinds of people, young and old, male and female. Epidemiological surveys report an increasing incidence of IGT and diabetes especially in younger people and more so in women than in men. Furthermore, the disease is not evenly spread amongst populations and the susceptibility to diabetes seems to be high in less priviledged populations. Our studies using rats have demonstrated a link between maternal protein deficiency, fetal and infant pancreatic structure and function, and subsequent glucose tolerance of the adult offspring, which can in turn pass on its effects to a second generation.

Given that the protein and nutritional intakes of expectant mothers in developing countries, as well as developed countries at times of food shortage, are often far below normal requirements, the possibility that maternal nutrient deficiency may affect susceptibility of offspring to chronic degenerative diseases such as diabetes and vascular complications in later life may have important implications for the future design of preventative programmes.

Figure: Study Design - Rat Groups

References:

Dahri S., Snoeck A., Reusens-Billen B., Remade C. & Hoet J.J. “Low protein diet during gestation in rates: its relevance to human non-insulin dependent diabetes. J. Physiology 647, 292P, 1993.

Desai M., Crowther N.J., Ozanne, S.E., Lucas A. & Hates C.N. Adult glucose and lipid metabolism may be programmed during fetal life. Biochemical Society Transactions 23, 331-335, 1995.

Reusens B., Dahri S., Snoeck A., Bennis-Taleb N., Ramacle C. & Hoet J.J. “Long term consequences of diabetes and its complications may have a fetal origin: experimental and epidemiological evidence. In Diabetes, (Ed. R.M. Cowett), Nestlutrition Workshop Series, Vol 35, pp. 187-197, 1995.

Discussion

Mr David Alnwick, Senior Advisor, Nutrition Section, UNICEF, New York

The presentation by Professor Hoet raises many important issues. This paper and other papers draw our attention to issues surrounding chronic and degenerative diseases in developing countries that perhaps some of us have overlooked. It is often assumed that if a child reaches the age of five, he or she will probably go on to live a relatively healthy life - we have been reminded today that this may rarely be true and perhaps the prospects for later life are, in fact, deteriorating.

The costs to society of caring for people with diseases such as diabetes and coronary vascular disease in developing countries are high, and the costs of preventing these diseases by adequate nutrition in utero or during pregnancy would be considerably less. A very strong cost-benefit argument could be made which would be in favour of improving nutrition in early life.

The important question is how to mobilize politicians who seem today to have a time horizon of three to five years, and so are looking for relatively short-term benefits. How do you convince the politician who has to stand for re-election in three or five years time that the benefits of a particular intervention are going to accrue to a population a generation hence - in 20 or 30 years' time?

One area where we have been successful in doing this is in the control of iodine deficiency disorders. The benefits from controlling IDD are not necessarily immediate. Some of these benefits - improved intellectual performance, and so on -accrue far later in life. Perhaps there are lessons from that particular area which could be applied to this.

Professor Hoet's reference to the important role of protein intake in pregnancy is indeed very interesting. The pendulum on the importance of protein swung one way, towards protein malnutrition and emphasis on protein supply, and then swung in the opposite direction towards the opinion that perhaps there were no significant human populations that were deficient in protein intake. There were considerable arguments about how protein requirements were defined. So certainly we need to take a careful look at the practical implications of Professor Hoet's findings. How does an 8% protein diet in rats compare with human requirements? The recent consensus in human nutrition circles has been that a net dietary protein intake of around 7-8% of total calories for human populations would be adequate to prevent protein deficiency. On the other hand, Professor Hoet's inference about the importance of protein and perhaps animal foods, reflects the feeling in other fields - vitamin A, iron, and the emerging enthusiasm for the importance of zinc. In each of these fields there seems to be a growing consensus that people whose diets are extremely restricted in animal food may have a great deal of difficulty in receiving sufficient quantities of some micronutrients for adequate growth and development. Given that populations of some of the largest countries in the world are largely vegetarian, and that these populations also have a very high prevalence of low birth weight, anaemia, and poor child growth, the importance of these observations is considerable.

The hypothesis is put forward that nutritional insults may be passed from one generation to another in a way which seems to be largely independent of genetic or social factors by programming that no amount of short-term social change will alter. A similar conclusion was reached by some speakers at an important IDECG meeting on the causes of linear growth retardation in developing countries*.

* The Proceedings of this IDECG Workshop, held in London from January 15-18, 1993 have been published as a supplement to the European Journal of Clinical Nutrition (Volume 48, Supplement 1, February 1994)

They suggested that we would not be able to reduce the prevalence of child stunting dramatically within one generation, because there was a generation to generation carry over. If this finding is correct, it clearly has very important implications for programme design in organizations which, like UNICEF, promote short-term goals for nutritional change.

The present consensus internationally is that all children brought up in adequate environments nutritionally grow more or less equally, at least for the first five or six years. The data supporting this conclusion are believed to be adequate, but there are inconsistencies, and discussions are taking place on collaborative ways to strengthen this data. It is certainly possible that many of the groups of so-called “elite” children in Africa and Asia, who have been found to be growing adequately, closely following NCHS reference curves, may themselves be the prodigy of elite parents. Perhaps we have been looking at the second generation rather than the first generation, and this again has important implications for what we can expect in terms of short-term nutritional improvements.

What are the practical implications of Professor Hoet's findings? They provide one more reason for donors and agencies to pay particular attention to improving nutrition in pregnancy. We need to reach a consensus on the long-term benefits of such programmes - in addition to reduction in low birthweight, improvements in young child growth, and improved maternal survival rates, we now have another powerful argument, that much later in life serious disease is reduced. We do not yet have sufficient consensus on exactly what benefits we can expect from nutritional improvements in pregnancy. Once we have that, we should advocate and inform the politicians.

PREVENTION AND THE ROLE OF NUTRITION

Dr George Beaton, Professor Emeritus, Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Canada

In opening today's symposium Dr Jervell portrayed the issues very well (see SCN News No. 13). As populations in the developing countries enhance their economic demand, they tend to seek out many of the lifestyle traits of Western society that we now accept as causally linked factors in non-communicable diseases.

He suggested that if nothing changes, deaths and disability from non-communicable diseases will surpass those from communicable diseases in the near future. This has major implications for health care resource demands. Even more important, it is likely to have a very undesirable effect on the distribution of these resources. The politically empowered middle and upper classes will be more affected and will be more effective in their demand for health services. This could result in diversion of resources away from the lower income groups, further denying them access to benefits of development.

If that was the total message of this symposium it would be important. Most of our time and attention is directed toward problems of deprivation and inadequacy. We need to be reminded that we must also face problems of excess - and problems associated with the very development we encourage. Is it really a good sign to see North American fast food chains appearing in developing countries? Should we attempt to promote certain types of free enterprise development and discourage other types of entrepreneurial activity? When one asks about possible preventive actions, that is what you are really asking. Have we learned anything that would allow us to encourage patterned development - do we have the ethical right to tell others no you shouldn't have access to all these tantalizing life-style features that we have - they're bad for you?!

I am not going to pursue those aspects of the topic. I merely state them openly so that all in this room will be compelled to recognize that in the end, that is what we are really talking about no matter how much we may care to hide it. It matters not whether you phrase this in terms of agriculture policy and animal food production or economic lending policy and the well-tested experience of Western economic development that carried with it health problems as well as benefits.

Yes, we could stop with the papers by Drs Jervell and Byers and spend the whole week debating their implications for development policy. However, when we also take into account the hypothesis put forward by Dr Hoet and hinted at by Dr Byers, we have an even more complex issue to address. Dr Hoet proposed that not only is the transition in lifestyle the major issue, but also that there may be “nutritional” factors that change risk factor sensitivity. Specifically, he proposed that factors operating during pregnancy or early postnatal development may predispose individuals toward diabetes and heart disease.

We do not yet know if this hypothesis is valid or, if it is, what nutritional factors are involved. Here I extract a quote from a paper from an amazing issue of the American Journal of Public Health (1995: 85:618-9) by A. D. Stein: “Nutritional epidemiologists have successfully identified many specific causal relationships between individual nutrients and specific pathology.... [cites folate and neural tube defects]... In many areas of nutritional epidemiology, uncertainty remains... Intriguing but by no means compelling, reports by Barker and his colleagues suggest that prenatal and early postnatal nutrition modifies risk of adult disease... the areas of uncertainty are often characterized by lack of specificity in putative risk factors, outcomes and biological mechanisms... the standard armamentarium of epidemiologic designs falls short.”

Some of you may have had the opportunity to read a paper by Phil James published in the Bulletin of the National Institute of Nutrition of India. He was commenting upon an increasing incidence and perhaps increased individual risk of heart disease in India. Dr James did not try to diagnose the situation or offer specific recommendations. Instead, in this article he set forth a large number of possible hypotheses, often interlinked, that might explain this phenomenon as a consequence of changes in lifestyle in an environment that carries many known risk factors. These hypotheses included some that might operate in utero and others that could operate regardless of the intrauterine environment.

The environmental variables that Phil James seemed to see as most important were dietary fat (and to a lesser extent protein), physical activity, and heavy smoking. I think that most others would look at dietary fat, physical activity and smoking as the three variables that warrant the greatest attention in assessing targets for possible preventive measures.

I do not want to dismiss the suggestion that susceptibility to these three variables might be conditioned by early developmental insults. Anthropometric deviation is the indicator identified in the studies described in this symposium. If we accept that in its simplest form then we can add it to the argument of Pelletier and colleagues who presented a revised approach to estimation of impact of malnutrition. Pelletier argues that this “suggests a much higher attribution of morbidity and mortality to malnutrition (marked by anthropometric indices)” J. Nutrition, Spring 1995.

It would appear that we have greatly underestimated the implications of early “malnutrition” on human health and wellbeing.

A first lesson of this symposium, then, is that we could be making a serious error if we attempt to treat problems of excess and problems of inadequacy as distinct entities. When we address population policies, we must recognize that both are often present together - and if we accept Dr Hoet's hypothesis they may coexist, at different times, in the same individuals.

A recent FAO/WHO report on fats and oils in human nutrition pointed out the obvious: noting that fat intakes in developing countries were often too low for child health while adult fat intakes should be kept low or perhaps be lowered, the committee commented: “Malnutrition is a crucial problem and increasing the amount of energy available should be a priority. Fats and oils play a crucial role in bringing about this increase. Nevertheless in developing countries policies designed to promote this increase can be a risk factor for urban populations who consume excess fat.”

The committee might equally well have stated the opposite: policies intended to reduce the dietary risk in urban populations might exacerbate the general problem.

Again in that remarkable issue of the American Journal of Public Health (1995, 85:690-4), we find a paper by Barry Popkin and Chinese colleagues Paernatakul, Ge and Fengying. These authors compared anthropometry recorded in 1989 and 1991 in 3,981 adults 20 - 45 years of age. Overall, the proportion classified as overweight and severely overweight increased from 9.3 to 11.2%, the proportion classed underweight fell from 8.5 to 8. For urban vs rural there were generally similar changes. In the high-income group overweight increased and underweight decreased. In the low-income group underweight and overweight increased.

China now has in place active policies intended to minimize the development of dietary and other risk factors - dietary policies and policies to encourage if not coerce physical activity. What these authors are pointing out is that while the policies may be operating as intended in some sectors of society they may be having differential effects in other sectors.

Some of you will recall that a few years ago, Dr Goplan proposed distinctly different dietary guidelines for rich and poor Indians. His approach was praised as taking into account the realities of the social setting of nutritional problems. It was also condemned as reflecting serious insensitivity to the wants, ambitions and rights of people - it seemingly perpetuated a situation of advantaged and disadvantaged. That is a real problem as we struggle with development policy and preventive action.

I want to illustrate another problem. Above I took a quote from a recent FAO/WHO report concerning achievement of goals for food intake. Now let us look at these goals a little more closely.

Toward dietary goals - dietary fat 1990 Lower limit of fat intake: adults: - group mean intake should have at least 15% of energy as fat - maximum of 10% energy as saturated fatty acids Upper limit of fat intake: adults: 30% of energy - group mean intake (If evidence accumulates, may fall to 25-30% energy) Who, 1990

Toward dietary goals - dietary fat 1994 Lower limit of fat intake: adults: - for most adults, dietary fat should supply at least 15% of energy - for women of reproductive age at least 20% energy as fat Concerted effort should be made to ensure adequate consumption of dietary fat among populations where less than 15% dietary energy is from fat. Children: - from start of weaning through at least 2 years, 30-40% energy from fat. Upper limit of fat intake: - active individuals up to 35% energy from fat (sfa under 10%) - sedentary individuals up to 30% Who, 1990

Consider differences in targets between child, adult, and pregnant woman - then recognize that these individuals live in the same household and share the same mix of foods. This is what the FAO/WHO committee recognized when it commented on conflicting policy.

It gets worse. There is confusion about the actual goals. I will illustrate this by comparing the two reports and suggest these seem to represent a truly major change in recommended goals - if the agencies accept the advice of the two committees. To illustrate this change I have to present distributions of the fat densities of the usual diets of individuals. For these illustrations, I assume normal distributions and 20% CV. These assumptions are reasonable based on examination of data from Canada, the US, and the Netherlands, the CVs are a bit high for rural Mexico, rural Kenya, and rural Egypt. The distribution assumptions may not apply everywhere but that is not important for this illustration.

DISTRIBUTIONS OF FAT DENSITY IMPLIED BY RECENT GOAL DEFINITIONS, WHO 1990

DISTRIBUTIONS OF FAT DENSITY IMPLIED BY RECENT GOAL DEFINITIONS, FAO/WHO 1994

For the FAO/WHO goal - move the tower cut off up for pregnancy, and move it still higher for children under two years of age.

The way the new FAO/WHO report is worded, it refers to intakes of individuals, not group means. It really says that there can only be a very narrow range of target intake distributions for all populations - those distributions will have mean intakes of about 22-25% of energy. This likely represents a substantial increase in fat for many of the developing countries and a very substantial reduction in fat for most of the industrialized countries. It would be interesting to do a calculation and see whether it implies a desirable net increase or decrease in fat intake for the world -and whatever that means in terms of development policies, agricultural policies, the various trade negotiations.

In this meeting at this time I do not intend to debate the relative merits of two reports from member agencies of the SCN - I do point out that there has been major shift in apparent targets and I point out that if we take the latest report as written, we have a critically important issue on our hands. It is an issue that certainly warrants a statement to the ACC.

Even if you discount the illustrations I gave or the specific recommendations of the FAO/WHO report and say “Beaton is making a mountain out of a mole hill” there remains a critical issue for us in thinking about prevention. In the last year or two we have focussed more and more heavily on the micronutrients. We have said repeatedly that we see a food-based approach as the sustainable path to solution. I think most of us recognize, but do not wish to admit, that the food-based approach for which we have the best evidence would be one that increased the intake of animal-source foods for most of the population of the world. We know also that if we succeed in improving effective demand through economic development, and allow it to happen, animal food intakes will rise.

How then do we marry that with our currently estimated goals for fat intake?

I want to come back to where we are. In keeping with the earlier papers I cited, Rey Martorell has published a review in Child Growth and Nutrition in Developing Countries which points to the importance of early childhood development. Martorell speculates on potential benefits of a strategy to promote healthy growth:

“- any of the strategies also have impact on other aspects of the child's environment - expect impact on multiple aspects of functional development;

- improved immune function and resistance to disease -reduced infant and child mortality rates;

- in long run, better school performance;

- increased work capacity as adults - reduced maternal/fetal risk in pregnancy.”

Martorell further emphasized that good physical growth results in increased human capital.

I cannot bypass another important paper by an individual here present. Nevin Scrimshaw notes that “... fulfillment of the genetic potential of individuals is impaired by malnutrition and other environmental factors throughout life...”. Further “... combined findings of early and later risk factors strengthen the conclusion that the bulk of so-called degenerative diseases and many other functional impairments in adult life occur because of environmental factors... the increase in meat, fat and calories consumed with rising affluence is particularly hazardous to formerly poorly nourished populations. (Am J Pub Hlth, 1995, 85, 622-4).

The constellation of papers all point in the same direction. Thus there is increased reason for attention to young child growth (prevention of 'PEM' in our conventional terminology).

Is there risk that we will direct too much attention to narrow goals we feel we can accomplish (e.g. control of micronutrient deficiencies) and not enough attention to the root problem we tend to avoid?

Somehow we must come back to more holistic approaches. We run a serious danger of unilateral approaches in single nutrient problems and forget that there may be implicit contradictions in what we are trying to advise countries to do.

POLICY FORMULATION COUNTRY LEVEL SOME PERCEIVED CHALLENGES How should countries existing income gradients in perceived problems? (Overweight in China as example). How do we, at the same time, urge a country to decrease fat intake for almost all and increase fat intake for 1 and 2 year olds? Or should we be doing that (if we are)? Do we have a strategy for “total nutrition” - micro - and macro- nutrients, infant young child and adult alike, that we are prepared to promote? I think the answer is no! Do we need something like this? How do we develop it?

Even worse, we might convince ourselves that the real answer lies in fabricated/engineered diets of the type that are beginning to appear on the North American market.

Conclusions

1. There is need to ensure we remember to address the broader and harder questions of prevention of PEM.

2. Avoid thinking of child problems and adult problems. They are population problems.

3. Solutions must be holistic.

Discussion

Dr Philip Musgrove, World Bank, Washington, D.C.

There are health gains to be had from improving nutrition, and postponing or reducing certain health problems later on, which might be very substantial. However, we are all going to die, and we may die of something quite expensive. In fact if we live long enough we are practically guaranteed to run into something expensive. So I just want to caution against the notion - and it would be nice if it were true - that when you improve some health problem in the world, this actually means less money gets spent on health care. Health care has the most unbelievably inelastic demand of anything you can imagine, and there is nothing to indicate that improving health means spending less. In fact the trend in the last 50 years has been in entirely the opposite direction.

This point is important for two reasons. The first is that it would be a mistake to sell nutritional improvement as a money saver. This will turn out not to be true. It should be sold as a health improver, and that, in fact, is very much the view taken by the World Bank in the World Development Report. Disability Adjusted Life Years (DALYs) represent the only real quantification of effects of health improvement. It is not a monetary measure, and we resisted any attempts whatever to say what a day is worth. It is true that a great many people reading about DALYs assume that they are some kind of productivity measure, and they are not. If they were productivity measures then a day out of the life of a rich person would be worth 10 or a hundred times as much as a day out of the life of a poor person.

The second reason for the importance of this point is that what counts for the purposes of designing policy is not total expenditure at all. The crucial connection between health gains and money expenditures, I still think, is cost effectiveness.

As we team more about how much “we are what we eat”, as we learn more about how complicated this is, as we learn more about how our grandmothers may have been right in telling us to eat a varied diet - the question arises of how this affects intervention choice. Deciding which interventions are more or less justified gets more complicated to handle

It seems to me that certain problems need more work. First of all we need to make sure that we have an accurate picture of what all the attributable risks are. This is not trivial. The burden of disease is calculated by disease - it has never been calculated adequately by different risks. Risk factors are difficult to add up as there are many different causes for a given effect.

For example, if two or three interventions can all reduce the size of a health problem, then it may be that the highest payoff will be to whichever intervention is used first, and the others will look very cost ineffective, because there is less of a problem to deal with. Whatever is done first is going to affect the cost-effectiveness of whatever is done second or third. That's inescapable. Some effort should go into working out what should be done first.

Then there's a problem which bothers me a lot, although it doesn't bother most of my colleagues. If you improve people's health, and this is particularly true of children, you get a whole variety of different kinds of effect. You get better health, which is valuable in itself. You get better educability, you probably get better adult health in the long run, you probably get better economic productivity, which is worth something, even if it doesn't belong in dollar calculations, and the adding up of those different kinds of benefits is a matter of their relative prices, and nobody knows what those relative prices ought to be.

To take a very simple example, the World Bank is getting extremely enthusiastic about what it calls early childhood development. But if you pose the question “which is better, graduating from another year of school, or spending three years completely free of disease?” nobody has any idea which one they would rather have, and so we cheerfully say that these are both good things, and we are going to get them both by promoting early childhood development. The stage of trading these outcomes off against each other hasn't really happened yet, and I think this is going to be very awkward because we don't know how to value different kinds of outcomes. The more it turns out that nutrition is behind all of these things, the more inescapable that particular question is going to be, I think. You have already raised it to a considerable extent just by showing that early childhood interventions may be affecting people a long time later in several different ways, including how much schooling they complete.

There are a couple of technical issues related to that. What you think about discount rates doesn't matter if you are talking about short intervals, but it matters greatly if you are talking very long intervals and so the question, does taking account of health effects 50 years later really add very much to the value today of a pregnancy or childhood intervention? At a high enough discount rate the answer is no, it doesn't make any difference at all. If just makes you feel good. At a low enough discount rate it actually changes substantially what you think the intervention is worth, and so arguments about the right way to calculate the burden of disease and the right way to calculate cost effectiveness matter more and more the longer the risk we are talking about.

The last thing I would like to touch on is the question of how do you change people's minds about things? How do you change their behaviour? Some things people will do without much persuasion - taking an injection, or swallowing a pill - because they don't need to change their habits. But we are talking here about substantial, lifelong changes and we are up against a problem of persuading people that something is good for them, but the same thing is not necessarily good for everybody. Children, pregnant women, non-pregnant women, men, and old people all have different requirements. People know this - it's not exactly news - but they don't necessarily act on it - and I think that's the biggest challenge. If the message were extremely simple, if it were just eat less fat, that would be easy to deal with, but if it's eat more fat when young, less when old, and watch out for what kind it is, it's no wonder that we don't know how to do this very well.