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The mutations of hunger

Malnutrition during the first years of life causes hypertension, diabetes and obesity in adolescents and adults

Miguel BoyayanWhen she was 15 months old Lia could barely sit, while most  children at her age are already beginning to walk. The reason for her late development was a lack of nutrients from pregnancy, which besides being the main cause of infantile mortality in developing countries may cause permanent health damage. After almost twenty years in which she has been investigating the effects of infant malnutrition, biologist Ana Lydia Sawaya, from the Physiology Department of the Federal University of São Paulo (Unifesp), can today explain why insufficient food has long-lasting effects and produces obese, diabetic adults with cardiovascular problems. In addition to detailing the physiology of malnutrition she has also invested in helping children like Lia recuperate and shown that treating them up to 6 years of age may avoid a large part of such problems.

Lia lives in a shanty town in the south of São Paulo, where Ana Lydia does most of her research. She chose to work with this population, not only because it is the one that most suffers from the consequences of poverty. “These are excluded people, outside the labor market and the reach of  public policies that could help them”, she explains. When investigating the health of residents in shanty towns in São Paulo and Maceió, where nearly 50% of the population live in a dire situation, Ana Lydia’s group saw that adolescents who were undernourished in their childhood present much higher obesity and hypertension rates than the rest of Brazilian society and have a greater risk of developing diabetes as adults.

Some of her more recent results show a high prevalence of hypertension in adolescents who were undernourished children (which is 21% in São Paulo). This is a very high figure when compared with adolescents that were not undernourished (7%). In short adults in Maceió this prevalence is 28.5% and affects women (44%) more than men (18%); in obese women it may reach 50%.

The Unifesp group discovered that this change in blood pressure occurs because of lesions that reduce the elasticity of the blood vessels and because of the malformation of the kidneys. Maria do Carmo Franco, a biologist who is a specialist in hypertension and who is one of the members of Ana Lydia’s team, is one of those responsible for explaining what happens in veins and arteries. She has dug deeply into the link between malnutrition and metabolism. She examined children between 10 and 13 who  were born with a low body weight, an indication of intrauterine malnutrition, and saw that in these children LDL cholesterol, which forms part of the cell membrane, reacts more than it should with free radicals, highly reactive oxygen molecules. This is what is called oxidative stress, which gives rise to even more reactive forms of oxygen that in turn damage the cells that line the blood vessels: this is just one step from developing fat deposits that alter the blood pressure and reduce the elasticity of the vessels, as results published this year in the magazine Pediatric Research suggest.

Damaged blood vessels, with a reduced capacity for expanding to let the blood pass, are just part of the problem. The biggest difficulty seems to be in the constitution of the kidneys, organs whose function is to clean  toxins from the blood . Malnutrition in the fetus may lead to the inadequate formation of the kidneys, which end up containing fewer functional units “nephrons” than normal. Ana Lydia’s team uses indirect ways for counting the number of nephrons, like measuring the level of toxins in the blood. “The ideal would be to do a biopsy, but I’m not going to take away part of the kidney of an already debilitated child”, she says. Even if each nephron works harder, the kidneys function like a not very efficient filter that limits the blood flow and ends up increasing the blood pressure. “This is the only sequel of undernourishment that we’re unable to recuperate”, regrets the biologist. As the nephrons are only formed during development of the fetus there is nothing that can be done to repair these kidneys. There is also no way of restoring the elasticity in the damaged blood vessels.

Malnutrition at the outset of infancy also causes deficiencies in the metabolism of sugar, which is controlled by the hormone, insulin, a lack of which is the main cause of diabetes, a sickness that in 2000 affected almost 5 million adults in Brazil; this figure is likely to rise to more than 11 million by 2030. In an article published in 2006 in the British Journal of Nutrition, Ana Lydia and her former student, Paula Martins, now a professor at Unifesp in the Santos Basin area, showed that insulin production was deficient in children who suffered from malnutrition at the beginning of their lives. This occurs because scarcity of food in the early phases of growth leads the organism to produce fewer beta cells in the pancreas, which produce insulin. To compensate, the organism of these children is more sensitive to the little insulin that is produced. In poor families that consume a modern sugar-heavy diet, this imbalance is even more serious.

Miguel BoyayanThe body tries to make up for the deficiency and makes every pancreatic cell work harder, and the price of all this additional effort is high. Nutritionist Telma Florêncio, from the Federal University of Alagoas, used short stature as a sign of malnutrition in the early years of life, because other studies have shown that the genetic contribution to growth is less than the environmental. She discovered that the organism in these short adults ends up becoming resistant to insulin, in such a way that even in high concentrations the hormone cannot help the body take advantage of the sugar that is available. Although the results that were published in a recent edition of the European Journal of Cardiovascular Prevention and Rehabilitation still do not allow for a clear explanation of the mechanism that causes this resistance, they do show that each pancreatic cell has to work harder and harder, which in the long term exhausts the pancreas. “This is immediately followed by diabetes”, concludes Ana Lydia.

The work of the Unifesp team revealed physiological mechanisms that cause hypertension and diabetes, but one of the root causes of these illnesses is also excess weight. The modern diet, where advertising and affordable prices encourage the consumption of food high in calories and low in nutritional quality (hamburgers, fried food, cookies and candies), is usually accused for the rise in obesity. But, according to the work of Telma, in extremely poor populations excess weight is not due to food excesses: the calories consumed by obese, short people were below the figure calculated as being necessary for their nutritional needs. Even though they are poorly nourished these people put on weight.

Telma examined the residents of a homeless person’s camp close to the university in Maceió, where living conditions were subhuman: whole families with a monthly per capita income less than US$ 10 lived in one-room tents made of plastic sheets. The results show that nearly 20% of the adults were short. Of these, 30% were overweight or obese and 16.3% undernourished. Therefore, the most serious nutritional problem in that population was obesity associated with infantile malnutrition: both short men and women had a greater tendency to be overweight than their neighbors, whose growth had been normal.

Obesity is a way in which the organism defends itself against poverty. According to Ana Lydia, in adverse situations the central nervous system regulates the metabolism to retain energy in the form of fat. She showed that the metabolism of short children is less efficient at breaking down accumulated body-fat. Furthermore, fat accumulation is governed by a reduction in the spending of energy and a drop in the production of the hormone, IGF-1, which promotes growth, and so the children are shorter. Metabolism studies have shown that this effect is more pronounced in girls than in boys and means that these children grow less and store the energy they ingest in the form of fat, provisions that may be essential for survival. Ana Lydia explains why the female body is so hungry for calories: “Women need more energy for pregnancy and breast-feeding”. Reserves accumulate above the waist area, and these are the reserves that release into the blood greater quantities of a type of lighter fat, which in turn accumulates in the blood vessels and gives rise to cardiovascular diseases and diabetes.

Malnutrition also leaves cognitive sequels. In a recent article in the Brazilian Journal of Maternal-Infantile Health, psychologist Mônica Miranda, from Unifesp, showed that children between 6 and 10 years old who have a poor  diet continuously from the start of their lives can barely remember things that they have just seen, have a more restricted vocabulary and suffer from anxiety. Another study, led by Luciana Melo de Lima, from the Otomed Clinic in Alagoas, showed that children with a history of malnutrition have more difficulty in learning to talk.

Lia, unable to sit unsupported and with a face lacking any expression whatsoever, arrived a little under a year ago at the Recovery and Nutritional Education Center (Cren), the Brazilian institution that is a benchmark in treating malnutrition, linked to Unifesp and founded in 1994 by Ana Lydia. Two months after the little girl was trying to take her first steps and today she is walking in a determined way, curiosity in her eyes and a toy cube in her hand to offer to the visitor in the room that functions as a nursery for children up to 2 years of age; other rooms house three more groups, divided by age, and with children up to 6 years old. Cren’s units deal with nearly 3,000 children a year, of whom 70% were already born with a lower than expected weight – 2.5 kg. Some of these children are sent by the health system. Most, however, are actively selected by the team that gets in touch with  leaders in each shanty town in the area in which they operate (the Cren from Vila Mariana works in the south of the city and the Cren from Vila Jacuí, which was inaugurated in 2006, in the east) and organizes collective efforts for weighing and measuring children. “It’s in the most unstructured families where the children who are seriously undernourished are found. There’s no good waiting for them to come to us; these people can’t even pay the bus fare”, says Ana Lydia. The group includes  undernourished children in its program and supplies travel vouchers so that they can appear at the Cren. “In some of these families there’s no father and the mother has problems with alcohol and drugs, so we have to mobilize other social assistance connections”, she adds. The census team, which includes doctors, nutritionists, social assistants and volunteers, prepares maps of each child’s social network. These are diagrams in which all those whom the child can count on are represented: relatives, neighbors, friends or institutions, like NGOs and government programs. Sometimes it is necessary to mobilize elements in this network to take the child to the Cren on a regular basis.

The small patients are attended in accordance with their degree of malnutrition. Some are dealt with in the daycare center, where they receive treatment for infections or parasitoses, as well as receiving advice about how to feed themselves well. For serious cases there is a day-hospital where children spend whole days receiving five meals a day in addition to medical, nutritional, pedagogic and, when necessary, psychological monitoring. The social services and the nutrition team offer cooking workshops where the mothers learn not only how to make nutritional, low cost meals, taking maximum advantage of common food, such as rice, beans and green vegetables, but also how to shop more efficiently and economically. Children also take part in food workshops in which they learn to recognize items for  a balanced diet and in the case of the older ones how to prepare some recipes.

Miguel BoyayanThe data collected over the 13 years of Cren show that even at 6 years old recovery is very satisfactory, but the ideal is that this happens by the time they reach 2. “That’s when food taste preferences are established”, explains Ana Lydia, “It’s only eating fruit and greens from early on that the conditioned reflex, which creates the desire to consume healthy food, will become established”. The treated children regain height growth faster than they gain weight. Even bone density, which loses quality with malnutrition, normalizes with the treatment they get at Cren. The improvement, however, is more marked in girls than in boys. “Physiologically we’re the strong sex”, says Ana Lydia. “The female body is smart; it recovers rapidly.”

Cren’s treatment does not just normalize size. Ana Lydia has shown that it is possible to recuperate the pancreas and avoid obesity. In doing so, a good number of the chronic illnesses that malnutrition causes in adults can also be avoided. After treatment the team monitors the children to check if the effects are sustained. The results of the periodic weighing and measuring are encouraging: they show that the physical improvement and the change in feeding habits continue in the home, even if the income and living conditions do not change.

Cren represents a successful experiment in São Paulo that will soon be implemented in Maceió. But it is not the only one. In the past initiatives have been created that have reached nationwide , but they were short-lived or were unable to cover the whole population. In 1999 the federal government instituted its Incentive for Combating Nutritional Needs (ICCN), in which underweight children would have to be registered. In some places, at least, the initiative was successful, as the article written by Rita Goulart, from the São Judas Tadeu University (São Paulo), in the Public Health Journals, shows. Researchers evaluated 724 children up to 2 years of age who were attended by the ICCN in the Sao Paulo State township of Mogi das Cruzes between 1999 and 2001. The program included evaluating and treating the health problems of the children, giving guidance to the mothers about feeding and supplying milk powder and soy oil (to increase the calorie level of the milk) to the registered children. The more serious their initial state of malnutrition the faster they grew.

Despite these successful experiments the ICCN was substituted by government social programs, like Food Grant and Family Grant. According to Ana Lydia, the Family Health Program, which provides for home visits, is a government initiative that could work to prevent malnutrition. However, in practice this is not happening. “The program’s structure doesn’t allow for systematic home visits in slum areas and it’s not possible to treat more serious malnutrition without a day hospital structure like that of Cren”, she regrets.

In contrast to the painful reality of hunger in the shanty towns, data from the Brazilian Institute of Geography and Statistics (IBGE) indicate that Brazil is going through a nutritional transition period, in which child malnutrition is becoming increasingly rare and obesity,  from adolescence, is growing in an alarming way. The research, the data of which was analyzed by Carlos Augusto Monteiro and Wolney Conde, from the School of Public Health of the University of São Paulo (USP), followed the standard IBGE methodology for household surveys – groups of dwellings are chosen at random in urban and rural areas, including slums and run-down tenement blocks. Over the last 30 years the results show a constant drop in the prevalence of malnutrition at the most vulnerable age – up to 5 – from 16.6% in 1974-1975 to 4.6% in 2002-2003. The research also showed that the situation is still worrying in the north and northeast regions, above all in the rural areas of the north where infant malnutrition affects 11% of the population. In the other regions, however, the research detected malnutrition in 3.5% of the sample, a figure that for Monteiro indicates that the problem is almost under control.

Of concern also is the increase in overweight people and obesity  from adolescence, up from 5.7% in 1974-1975 to 16.7% in 2002-2003, which according to Monteiro happens in all regions and economic levels and results from unsuitable food and little physical activity. These and other data are in a national survey carried out in 2006 by a consortium of academic institutions led by the Brazilian Center for Analysis and Planning (Cebrap), the results of which Monteiro is still analyzing.

Ana Lydia, however, argues that these data do not reflect the Brazilian reality. “A census is done according to address or other official locator. When you work with misery and slums these people don’t exist; they have no address, they have no jobs, and they have no identity card. Working with national averages makes no sense in Brazil, with the huge income inequality and social exclusion we have.” For Ana Lydia malnutrition and obesity are not opposite illnesses. On the contrary, the fact that the former causes the latter indicates that they are associated with the same physiological mechanisms. “Malnutrition and obesity coexist in slums in the same families”, adds the researcher, who emphasizes the fact that no one knows how many undernourished people there are in Brazil. “We don’t even know how many people live in the slums in São Paulo – estimates vary between 1.1 million and 2 million”; what does that say about the rest of the country.  How can we say we’ve covered their nutritional situation?”