Posts Tagged ‘Kwashiorkor’

The Significant Burden of Childhood Malnutrition and Stunting

Curator: Larry H. Bernstein, MD, FCAP


Quite a few  trace elements or micronutrients—vitamins and minerals—are important for health. Three very important micronutrient deficiencies in terms of health consequences for poor people in developing countries are:


  • In developing countries every second pregnant woman and about 40% of preschool children are estimated to be anemic.
  • In many developing countries, iron deficiency anemia is aggravated by worm infections, malaria and other infectious diseases such as HIV and tuberculosis.
  • The major health consequences include poor pregnancy outcome, impaired physical and cognitive development, increased risk of morbidity in children and reduced work productivity in adults. Anemia contributes to 20% of all maternal deaths. (WHO Iron Deficiency Anemia)

Vitamin A

  • Vitamin A deficiency  can cause night blindness and reduces the body’s resistance to disease. In children Vitamin A deficiency can also cause growth retardation.
  • An estimated 250 million preschool children are vitamin A deficient. An estimated 250,000 to 500 000 vitamin A-deficient children become blind every year, half of them dying within 12 months of losing their sight. (WHO Vitamin A Deficiencies)


  • Iodine deficiency is one of the main cause of impaired cognitive development in children.
  • Serious iodine deficiency during pregnancy can result in stillbirth, spontaneous abortion, and congenital abnormalities such as cretinism, a grave, irreversible form of mental retardation that affects people living in iodine-deficient areas of Africa and Asia.
  • Iodine deficiency has a simple solution: iodized salt. Thanks to this intervention, the number of countries where iodine deficiency is a public health problem has halved over the past decade.  However 54 countries still have a serious iodine deficiency problem. (WHO Iodine Deficiencies)

Children and hunger

Children are the most visible victims of undernutrition.  Black et al (2013) estimate that undernutrition in the aggregate—including fetal growth restriction, stunting, wasting, and deficiencies of vitamin A and zinc along with suboptimum breastfeeding—is a cause of 3·1 million child deaths annually or 45% of all child deaths in 2011 (Black et al. 2013).  Undernutrition magnifies the effect of every disease, including measles and malaria. The estimated proportions of deaths in which undernutrition is an underlying cause are roughly similar for diarrhea (61%), malaria (57%), pneumonia (52%), and measles (45%) (Black 2003, Bryce 2005). Malnutrition can also be caused by diseases, such as the diseases that cause diarrhea, by reducing the body’s ability to convert food into usable nutrients.


  • Globally 161 million under-five year olds were estimated to be stunted in 2013.
  • The global trend in stunting prevalence and numbers affected is decreasing. Between 2000 and 2013 stunting prevalence declined from 33% to 25% and numbers declined from 199 million to 161 million.
  • In 2013, about half of all stunted children lived in Asia and over one third in Africa. (UNICEF et al. 2014b)

Wasting and severe wasting ·

  • Globally, 51 million under-five year olds were wasted and 17 million were severely wasted in 2013.
  • Globally, wasting prevalence in 2013 was estimated at almost 8% and nearly a third of that was for severe wasting, totaling 3%. In 2013, approximately two thirds of all wasted children lived in Asia and almost one third in Africa, with similar proportions for severely wasted children. (UNICEF et al. 2014b)
  •  In 2013, approximately two thirds of all wasted children lived in Asia and almost one third in Africa, with similar proportions for severely wasted children. (UNICEF et al. 2014b)

Under-five Protein Energy Malnutrition Admitted at the University of In Nigeria Teaching Hospital, Enugu: a 10 year retrospective review

Agozie C Ubesie12*, Ngozi S Ibeziako12, Chika I Ndiokwelu3, Chinyeaka M Uzoka3 andChinelo A Nwafor3

Nutrition Journal 2012, 11:43  doi:10.1186/1475-2891-11-43

To determine the prevalence, risk factors, co-morbidities and case fatality rates of Protein Energy Malnutrition (PEM) admissions at the paediatric ward of the University of Nigeria Teaching Hospital Enugu, South-east Nigeria over a 10 year period.


A retrospective study using case Notes, admission and mortality registers retrieved from the Hospital’s Medical Records Department.


All children aged 0 to 59 months admitted into the hospital on account of PEM between 1996 and 2005.


A total of 212 children with PEM were admitted during the period under review comprising of 127 (59.9%) males and 85(40.1%) females. The most common age groups with PEM were 6 to 12 months (55.7%) and 13 to 24 months (36.8%). Marasmus (34.9%) was the most common form of PEM noted in this review. Diarrhea and malaria were the most common associated co-morbidities. Majority (64.9%) of the patients were from the lower socio-economic class. The overall case fatality rate was 40.1% which was slightly higher among males (50.9%). Mortality in those with marasmic-kwashiokor and in the unclassified group was 53.3% and 54.5% respectively.


Most of the admissions and case fatality were noted in those aged 6 to 24 months which coincides with the weaning period. Marasmic-kwashiokor is associated with higher case fatality rate than other forms of PEM. We suggest strengthening of the infant feeding practices by promoting exclusive breastfeeding for the first six months of life, followed by appropriate weaning with continued breast feeding. Under-five children should be screened for PEM at the community level for early diagnosis and prompt management as a way of reducing the high mortality associated with admitted severe cases.

Globally, PEM continues to be a major health burden in developing countries and the most important risk factor for illnesses and death especially among young children [1]. The World Health Organization estimates that about 60% of all deaths, occurring among children aged less than five years in developing countries, could be attributed to malnutrition [2]. The improvement of nutrition therefore, is the main prerequisite for the reduction of high infant and under five mortality rates, the assurance of physical growth, social and mental development of children as well as academic achievement [3]. Sub-saharan Africa bears the brunt of PEM in the world. On the average, the PEM associated mortality in sub-Saharan Africa is between 25 and 35% [4,5]. In Nigeria, 22 to 40% of under-five mortality has been attributed to PEM [6]. PEM is also associated with a number of co-morbidities such as lower respiratory tract infections including tuberculosis, diarrhea diseases, malaria and anaemia [7,8]. These co-morbidities may prolong the duration of hospital stay and death among affected children.

There is a knowledge gap on the incidence and outcome of PEM seen in the Nigerian tertiary health facilities. In this study, the type of PEM among admitted under-five children, the associated morbidities, and duration of hospitalization and outcome at the University of Nigeria Teaching Hospital Enugu over a 10 year period is reviewed.

Relevant information was extracted from each retrieved case file and/or hospital registers and transferred into the proforma. Diagnosis of PEM was based on the Modified Wellcome Classification because it was the method used for clinical diagnosis by the clinicians. This classified PEM into kwashiorkor, underweight kwashiorkor, underweight, marasmus, marasmic kwashiorkor and there was also provision for unclassified PEM. Marasmus and the various forms of kwashiorkor are part of the recently defined Severe Acute Malnutrition (SAM) by the World Health Organization (WHO). The WHO defined SAM by a very low weight for height (below -3z scores of the median WHO growth standards), visible severe wasting or the presence of nutritional oedema [11,12]. Modified Wellcome classification uses weight for age and the presence or absence of oedema to classify PEM. The weights were measured using infant weighing scales (Waymaster) and stadiometers (Health Scale) depending on the age of the child. A total of 212 proforma were completed covering the entire period of the study.

Diagnosis of HIV was made using Enzyme Linked Immunosorbent Assay [ELISA] and Westerblot. In children aged less than 18 months, positive antibody test was combined with clinical features to make presumptive diagnosis of HIV infection. Diagnosis of malaria was confirmed using blood film and bronchopneumonia using chest X-ray. Diarrhea was defined as passage of watery or loose stools or an increase in frequency above normal for a child. Severe anaemia was defined using a packed cell volume of less than 15%. Sepsis was defined as clinical features of systemic inflammatory response (fever, tachycardia, tachypnea, leukocytosis or leukopenia) associated with infection. Diagnosis of tuberculosis was made in the presence of chronic cough that have lasted for more three weeks supported by varied combination of the following: positive family history of tuberculosis, positive mantoux, suggestive chest X-ray and elevated erythrocyte sedimentation rate. Diagnosis of scabies was clinical based on the typical itching papular rash located at the intertrigous areas. Chronic suppurative otitis media and rickets were suspected clinically and confirmed by culture of ear swab and X-ray of the limbs respectively.


A total of 7703 children were admitted into the paediatric wards and 212 of them were cases of PEM during the period under review. This represented about 2.8% of the total paediatric admissions. One hundred and twenty seven (59.9%) were males while 85 (40.1) were females giving a male: female ratio of 1: 0.7. The age group studied was 6 to 59 months (under-5). The mean age of the participants was 15.4 ± 9.3 months.

PEM and demography

PEM was most common among the age groups 6 to 12 and 13 to 24 months, and these accounted for 55.7% and 36.8% of the study population respectively. There was however, no statistically significant difference between the age groups and various forms of PEM as shown in Table 1(χ² = 19.38, df =16, p = 0. 249). The most common form of PEM noted in this review was marasmus (34.9%). Except for marasmic-kwashiokor, more males than females had more of all the various types although this was not statistically significant (χ² = 8.382, df =4, p = 0. 079) as shown in Table2. Admissions for PEM were recorded more in 1996, 1999 and 2004 (15.1, 13.7 and 12.3% respectively), but there were no consistent pattern in the yearly admissions of children with PEM during the period under review (Figure 1).

PEM admissions according to the age groups (months)
PEM type 0-12 m (%) 13-24 m (%) 25-36 m (%) 37-60 m (%) 49-60 m (%)
Kwashiokor 16 (13.6) 19 (24.4) 3 (33.3) 1 (33.3) 1 (25)
Underweight 11 (9.3) 6 (7.7) 0 (0) 0 (0) 0 (0)
Marasmic-kwash 6 (5.1) 8 (10.3) 0 (0) 1 (33.3) 0 (0)
Marasmus 48 (40.7) 24 (30.8) 2 (22.2) 0 (0) 0 (0)
Unclassified 37 (31.4) 21 (26.9) 4 (44.4) 1 (33.3) 3 (75)
Total 118 (100) 78 (100) 9 (100) 3(100) 4 (100)

χ² = 19.38, df =16, P = 0. 249.

Table 3
The associated co-morbidities seen among patients
Co-morbidity Frequency
Diarrhea 48 (72.2)
Malaria 29 (43.9)
Sepsis 25 (37.9)
Severe anaemia 16 (24.2)
Bronchopneumonia. 11 (16.7)
HIV 9 (13.6)
Tuberculosis 8 (12.1)
other 5 (7.5)

The table shows the associated co-morbidities noted in the patients.

Table 4
Prevalence of PEM by breastfeeding pattern
Breastfeeding pattern Prevalence 95% Confidence Intervals
Exclusive breast feeding for 0–3 months 18.9 11.2 – 26.6
Predominant breastfeeding 0–3 months 48.6 38.8 – 58.4
Predominant breastfeeding 4–6 months 24.3 15.9 – 32.7
Breast milk substitutes 8.1 2.7 – 13.5

The table shows the prevalence of the various pattern of feeding for the children during their early infancy. The 95% confidence interval is also reported.

Ubesie et al.

Ubesie et al. Nutrition Journal 2012 11:43   doi:10.1186/1475-2891-11-43

Prognostic indicators

The duration of hospitalization was available in only 84 subjects and ranged from 0 to 62 days. The mean duration of hospitalization was 16 ± 15 days. Kwashiokor patients had the highest mean hospitalization days of 19.15 days while marasmic and underweight patients had the least days of 14.52 and 14.55 days respectively. There was no statistically significant difference in the mean hospitalization days for the various types of PEM (F = 0.317, df =4, P = 0. 866). A total of 85 (40.1%) children died while on admission, 124 (58.5%) recovered and were discharged home while 3 (1.4%) were discharged against medical advice. Mortality was higher among the males (50.9%) than females (34.1%) although this was not statistically significant (χ² = 0.723, df =2, P = 0. 697). Most of the deaths were recorded in the age groups 0–12 (55.3%) and 13–24 (36.5%) months although this difference was not statistically significant (χ² = 10.98, df =8, p = 0. 203). The marasmic-kwashiokor and unclassified groups had higher mortality rates (53.3% and 54.5% respectively) than the marasmus (37.8%) or kwashiorkor groups (30%). There was a statistically significant difference in the mortality rates of the various types of PEM as shown in Table 5 (χ² = 17.26, df =4, p = 0. 002) The number of complications ranged from none to four. Kwashiokor has the highest mean number of complications (2.06) while unclassified had the least number of 1.26. There was a statistically significant difference in the number of complications and the various PEM (F = 8.92, df =4, P <0.05)

High PEM associated mortality

The overall mortality in our study was 40.1% which although lower than the WHO estimated 60%[2] is still very high. Studies conducted in various parts of Africa have documented unacceptable high mortality rates among children admitted for PEM. In Oshogbo, South West Nigeria, Ibekwe and Ashworth [6] documented an average mortality rate of 22% over a five year period among 803 children admitted for PEM in a Nutritional Rehabilitation Center. Similarly, in a hospital based study in north-eastern Zambia, involving children below the age of five years, Gernaat et al.[4] documented an overall mortality rate of 25.8% among 288 children admitted for various types of severe/complicated malnutrition . Higher mortality rate for marasmic kwashiorkor than marasmus or kwashiorkor was noted in this review. Gernaat et al.[4] noted similar finding in their review among Zambian children admitted and managed for PEM. This reason for this is unclear. However, Ibekwe and Ashworth [6] did note that PEM associated mortality among oedematous patients was significantly higher compared to those with marasmus. It can be argued therefore, that presence of oedema in a malnourished child connotes poor prognosis. The mean duration of hospitalization was 16 days which is similar to 13.1 and 14.3 days reported by Cartmell et al. [13] but differs from the 35 days reported by Ibekwe and Ashworth [6]. Both this review and the study by Cartmell et al. were hospital based while that of Ibekwe and Ashworth was conducted in a Nutrition Rehabilitation Center. The pressure on bed spaces in a hospital setting could have contributed to earlier discharges in hospital settings.

Associated risk factors for PEM

Our review noted that PEM was more common among children from the lower social class (69.4%) and those predominantly breast fed for three months or less (48.6%) compared to exclusively breast fed children (18.9%). The reason for this may not be unconnected to the fact that poor families have low purchasing power for adequate nutritious foods for their families. Illiteracy on the other hand, may influence feeding practices. The low rate of exclusive breast feeding noted in this review despite the Baby Friendly Initiatives is also very worrisome. Poverty and illiteracy as risk factors for PEM have been documented in the literature. . In a case control study conducted in Dhaka, Bangladesh which involved children aged six to 24 months, Nahar et al.[15] compared 507 children with weight-for-age z-score (WAZ) < −3 matched for age, sex and place of residence with 500 children whose weight-for-age z-score (WAZ) were > −2.5 . They documented that severely-underweight children were more likely to have: undernourished poorly educated teenage mothers, history of shorter duration of predominant breastfeeding, and fathers who were poorly educated and unskilled day-labourers [15].

Diarrhea, malaria, sepsis and severe anaemia were the most prevalent associated co-morbidities from our review in that order. In Maputo, the most prevalent co-morbidities associated with PEM by Cartmell et al. were anaemia, bronchopneumonia, malaria and diarrhea. The prevalence of human immune deficiency virus (HIV) from our review was 13.6% and this compares to a prevalence of 12% in the Maputo study. This finding underscored the high rate of HIV infection among children with severe forms of PEM and the need to routinely screen such children for HIV when they present at a health facility.


Younger children aged less than two years accounted for most of the admissions in this review. Marasmic-kwashiokor was associated with higher case fatality rate than other types of PEM. There is need therefore to strengthen the infant feeding practices by promoting exclusive breastfeeding for the first 6 months of life, followed by appropriate weaning with continued breast feeding till second year of life. PEM was associated with high rate of mortality in this hospital setting and preventive strategies need to be emphasized instead.

Below are 10 interesting facts about poverty and malnutrition.

  1. Malnutrition takes two general forms. Protein-energy malnutrition, which is basically a lack of calories and protein. This form of malnutrition is the most lethal and is the type of malnutrition that is referred to when world hunger is discussed. The second type of malnutrition is micronutrient or vitamin and mineral deficiency.
  2. According to The United Nations Food and Agriculture Organization, it is estimated that nearly 870 million people of the 7.1 billion people in the world – or one in eight – were suffering from chronic undernourishment in 2010-2012.
  3. Poverty and malnutrition have a direct link – poverty is the main and principal cause of malnutrition. The World Bank estimated that in 2008 that there were about 1.35 million poor people in developing countries who live on $1.25 a day or less.
  4. In addition to poverty, the other main causes of malnutrition are harmful economic systems, war and conflict and climate change.
  5. The countries with the highest rates of malnutrition also have the lowest economic indicators.
  6. Children are the most vulnerable victims of malnutrition.  Poor nutrition plays a role in at least half of the 10.9 million child deaths each year.
  7. Mothers who lack access to proper nutrients bear malnourished children. These children face greater challenges in their ability to learn and thrive. They are more susceptible to illness and disease. Their compromised opportunities for healthy development and mental and physical agility usually means the cycle of poverty continues.
  8. In another link between poverty and malnutrition, the WHO reports that one out of three people in developing countries are affected by vitamin and mineral deficiencies.
  9. The world produces enough food to feed everyone. The real problem is that many people in the world do not have sufficient land to grow or income to purchase enough food. Poverty and malnutrition can create a self-sustaining cycle where there is never enough security or stability for recovery of health or economic development.
  10. Some countries address the problem of poverty and malnutrition by administering programs that provide assistance to those who suffer from a lack of nutrients in their diet by offering dietary supplements and fortified foods. This is seen as a cost-effective strategy in combating poverty and malnutrition.

– Nina Verfaillie

Chapter 12. Protein-energy malnutrition

Protein-energy malnutrition (PEM) in young children is currently the most important nutritional problem in most countries in Asia, Latin America, the Near East and Africa. Energy deficiency is the major cause. No accurate figures exist on the world prevalence of PEM, but World Health Organization (WHO) estimates suggest that the prevalence of PEM in children under five years of age in developing countries has fallen progressively, from 42.6 percent in 1975 to 34.6 percent in 1995. However, in some regions this fall in percentage has not been as rapid as the rise in population; thus in some regions, such as Africa and South Asia, the number of malnourished children has in fact risen. In fact the number of underweight children worldwide has risen from 195 million in 1975 to an estimated 200 million at the end of 1994, which means that more than one-third of the world’s under-five population is still malnourished.

Failure to grow adequately is the first and most important manifestation of PEM. It often results from consuming too little food, especially energy, and is frequently aggravated by infections. A child who manifests growth failure may be shorter in length or height or lighter in weight than expected for a child of his or her age, or may be thinner than expected for height.

The conceptual framework described in Chapter 1 suggests that there are three necessary conditions to prevent malnutrition or growth failure:

  • adequate food availability and consumption;
  • good health and access to medical care; and
  • adequate care and feeding practices.

If any one of these is absent, PEM is a likely outcome.

The term protein-energy malnutrition entered the medical literature fairly recently, but the condition has been known for many years. In earlier literature it was called by other names, including protein-calorie malnutrition (PCM) and protein-energy deficiency.

The term PEM is used to describe a broad array of clinical conditions ranging from the mild to the serious. At one end of the spectrum, mild PEM manifests itself mainly as poor physical growth in children; at the other end of the spectrum, kwashiorkor (characterized by the presence of oedema) and nutritional marasmus (characterized by severe wasting) have high case fatality rates.

It has been known for centuries that grossly inadequate food intake during famine and food shortages leads to weight loss and wasting and eventually to death from starvation. However, it was not until the 1930s that Cicely Williams, working in Ghana, described in detail the condition she termed “kwashiorkor” (using the local Ga word meaning “the disease of the displaced child”). In the 1950s kwashiorkor began to get a great deal of attention. It was often described as the most important form of malnutrition, and it was believed to be caused mainly by protein deficiency. The solution seemed to be to make more protein-rich foods available to children at risk. This stress on kwashiorkor and on protein led to a relative neglect of nutritional marasmus and adequate food and energy intakes for children.

The current view is that most PEM is the result of inadequate intake or poor utilization of food and energy, not a deficiency of one nutrient and not usually simply a lack of dietary protein. It has also been increasingly realized that infections contribute importantly to PEM. Nutritional marasmus is now recognized to be often more prevalent than kwashiorkor. It is unknown why a given child may develop one syndrome as opposed to the other, and it is now seen that these two serious clinical forms of PEM constitute only the small tip of the iceberg. In most populations studied in poor countries, the point prevalence rate for kwashiorkor and nutritional marasmus combined is 1 to 5 percent, whereas 30 to 70 percent of children up to five years of age manifest what is now termed mild or moderate PEM, diagnosed mainly on the basis of anthropometric measurements.

Causes and epidemiology

PEM, unlike the other important nutritional deficiency diseases, is a macronutrient deficiency, not a micronutrient deficiency. Although termed PEM, it is now generally accepted to stem in most cases from energy deficiency, often caused by insufficient food intake. Energy deficiency is more important and more common than protein deficiency. It is very often associated with infections and with micronutrient deficiencies. Inadequate care, for example infrequent feeding, may play a part.

The cause of PEM (and of some other deficiency diseases prevalent in developing countries) should not, however, be viewed simply in terms of inadequate intake of nutrients. For satisfactory nutrition, foods and the nutrients they contain must be available to the family in adequate quantity; the correct balance of foods and nutrients must be fed at the right intervals; the individual must have an appetite to consume the food; there must be proper digestion and absorption of the nutrients in the food; the metabolism of the person must be reasonably normal; and there should be no conditions that prevent body cells from utilizing the nutrients or that result in abnormal losses of nutrients. Factors that adversely influence any of these requisites can be causes of malnutrition, particularly PEM. The aetiology, therefore, can be complex. Certain factors that contribute to PEM, particularly in the young child, are related to the host, the agent (the diet) and the environment. The underlying causes could also be categorized as those related to the child’s food security, health (including protection from infections and appropriate treatment of illness) and care, including maternal and family practices such as those related to frequency of feeding, breastfeeding and weaning.
Protein-Energy Malnutrition

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Romesh Khardori, MD, PhD, FACP

The World Health Organization (WHO)[1] defines malnutrition as “the cellular imbalance between the supply of nutrients and energy and the body’s demand for them to ensure growth, maintenance, and specific functions.” The term protein-energy malnutrition (PEM) applies to a group of related disorders that include marasmus, kwashiorkor (see the images below), and intermediate states of marasmus-kwashiorkor. The term marasmus is derived from the Greek word marasmos, which means withering or wasting. Marasmus involves inadequate intake of protein and calories and is characterized by emaciation. The term kwashiorkor is taken from the Ga language of Ghana and means “the sickness of the weaning.” Williams first used the term in 1933, and it refers to an inadequate protein intake with reasonable caloric (energy) intake. Edema is characteristic of kwashiorkor but is absent in marasmus.

This photograph shows children and a nurse attendant at a Nigerian orphanage in the late 1960s. Notice four of the children with gray-blond hair, a symptom of the protein-deficiency disease kwashiorkor. Image courtesy of Dr. Lyle Conrad and the CDC Public Health Image Library.

This late 1960s photograph shows a seated, listless child who was among many kwashiorkor cases found in Nigerian relief camps during the Nigerian-Biafran war. Kwashiorkor is a disease brought on due to a severe dietary protein deficiency, and this child, whose diet fit such a deficiency profile, presented with symptoms including edema of legs and feet, light-colored, thinning hair, anemia, a pot-belly, and shiny skin. Image courtesy of Dr. Lyle Conrad and the CDC Public Health Image Library.

Studies suggest that marasmus represents an adaptive response to starvation, whereas kwashiorkor represents a maladaptive response to starvation. Children may present with a mixed picture of marasmus and kwashiorkor, and children may present with milder forms of malnutrition. For this reason, Jelliffe suggested the term protein-calorie (energy) malnutrition to include both entities.

Although protein-energy malnutrition affects virtually every organ system, this article primarily focuses on its cutaneous manifestations. Patients with protein-energy malnutrition may also have deficiencies of vitamins, essential fatty acids, and trace elements, all of which may contribute to their dermatosis.

In general, marasmus is an insufficient energy intake to match the body’s requirements. As a result, the body draws on its own stores, resulting in emaciation. In kwashiorkor, adequate carbohydrate consumption and decreased protein intake lead to decreased synthesis of visceral proteins. The resulting hypoalbuminemia contributes to extravascular fluid accumulation. Impaired synthesis of B-lipoprotein produces a fatty liver.

Protein-energy malnutrition also involves an inadequate intake of many essential nutrients. Low serum levels of zinc have been implicated as the cause of skin ulceration in many patients. In a 1979 study of 42 children with marasmus, investigators found that only those children with low serum levels of zinc developed skin ulceration. Serum levels of zinc correlated closely with the presence of edema, stunting of growth, and severe wasting. The classic “mosaic skin” and “flaky paint” dermatosis of kwashiorkor bears considerable resemblance to the skin changes of acrodermatitis enteropathica, the dermatosis of zinc deficiency.

In 2007, Lin et al[2] stated that “a prospective assessment of food and nutrient intake in a population of Malawian children at risk for kwashiorkor” found “no association between the development of kwashiorkor and the consumption of any food or nutrient.”

Marasmus and kwashiorkor can both be associated with impaired glucose clearance that relates to dysfunction of pancreatic beta-cells.[3] In utero, plastic mechanisms appear to operate, adjusting metabolic physiology and adapting postnatal undernutrition and malnutrition to define whether marasmus and kwashiorkor will develop.[4]

United States

Protein-energy malnutrition is the most common form of nutritional deficiency among patients who are hospitalized in the United States. As many as half of all patients admitted to the hospital have malnutrition to some degree. In a recent survey in a large children’s hospital, the prevalence of acute and chronic protein-energy malnutrition was more than one half. This is very much a disease that occurs in 21st century America, and a case in an 8-month-old child in suburban Detroit, Mich, was reported in 2010.[9] Additional cases of kwashiorkor have been noted to occur in the United States. An interesting report of a baby with a clinical picture imitating Stevens-Johnson syndrome but who in fact had kwashiorkor has been noted.[10] Babies solely fed on rice milk can develop kwashiorkor even in the United States.

In a survey focusing on low-income areas of the United States, 22-35% of children aged 2-6 years were below the 15th percentile for weight. Another survey showed that 11% of children in low-income areas had height-for-age measurements below the 5th percentile. Poor growth is seen in 10% of children in rural populations.

In hospitalized elderly persons, up to 55% are undernourished. Up to 85% of institutionalized elderly persons are undernourished. Studies have shown that up to 50% have vitamin and mineral intake that is less than the recommended dietary allowance and up to 30% of elderly persons have below-normal levels of vitamins and minerals.


In 2000, the WHO[11] estimated that malnourished children numbered 181.9 million (32%) in developing countries. In addition, an estimated 149.6 million children younger than 5 years are malnourished when measured in terms of weight for age. In south central Asia and eastern Africa, about half the children have growth retardation due to protein-energy malnutrition. This figure is 5 times the prevalence in the western world.

A cross-sectional study of Palestinian adolescents found that 55.66% of boys and 64.81% of girls had inadequate energy intake, with inadequate protein intake in 15.07% of boys and 43.08% of girls. The recommended daily allowance for micronutrients was met by less than 80% of the study subjects.[12]


Approximately 50% of the 10 million deaths each year in developing countries occur because of malnutrition in children younger than 5 years. In kwashiorkor, mortality tends to decrease as the age of onset increases.


Dermatologic findings appear more significant and occur more frequently among darker-skinned peoples. This finding is likely explained by the greater prevalence and the increased severity of protein-energy malnutrition in developing countries and not to a difference in racial susceptibility.

The hungry and forgotten


chinese child

chinese child

Pilot projects in cooperation with the Ministry of Health have demonstrated the effectiveness of Ying Yang Bao, a simple easy-to-use complementary food supplement, in preventing and controlling childhood malnutrition.UNICEF has been supporting intensive efforts on finding solutions.

Even where children get the calories they need—as most do in rural China—they are not being fed the right things. In one study of 1,800 infants in rural Shaanxi province in China’s north-west, 49% were anaemic and 40% were significantly hampered in developing either cognitive or motor skills. Fewer than one in ten were stunted or wasting, meaning that in most cases the problem was not lack of calories, but lack of nutrients.

China shares this affliction with much of the developing world. But it has the resources to respond. Parents have the means to feed their babies properly. And with a relatively modest investment, the government could do a better job of improving childhood nutrition. The difficulties lie in educating parents—and officials.

“Babies are probably 50% malnourished” in poor rural areas, says Scott Rozelle, co-director of the Rural Education Action Programme (REAP), a research outfit at Stanford University which has done extensive tests on anaemia in rural China. “But almost no mums are malnourished.” Mr Rozelle says that in one of his surveys rural mothers showed a better understanding of how to feed pigs than babies: 71% said pigs need micronutrients, whereas only 20% said babies need them.

Mr Lu’s charity and REAP argue that a nutritional supplement called ying yang bao should be available to rural mothers. A powdery concoction of soyabeans, iron, zinc, calcium and vitamins, it is supposed to be sprinkled on food once a day. Each packet costs less than one yuan (16 cents) to produce and one yuan to distribute, paid by the government.

Trials conducted since 2006 have consistently shown that ying yang bao reduces anaemia and improves growth and development in infants and toddlers. But persuading parents of this (or grandparents, if the parents are off working in cities) has not been easy. About half give up feeding it to their children. “Poor people feel very suspicious”, Mr Lu says. They wonder if free supplements are unsafe, or fake. “Then they worry will we charge later?”

This may be the legacy in rural China of years of seeing government invest little—and often charge a lot—for basic services. Moreover, at the local level the workers who are meant to help mothers may well be family-planning officials responsible for controlling population, a role that hardly inspires trust.

At higher levels of government, too, officials need a lot of persuading that nutrition programmes are not a waste of public money. In 2011 China began instituting a programme similar to America’s federal school-lunch programme for the poor, at a cost of 16 billion yuan ($2.6 billion) a year. But one assessment suggests that perhaps half the schools are providing substandard, uncooked meals, partly because some local governments refuse to foot the bill for kitchens and cooks.

In 2012 the health ministry made a modest investment of 100m yuan to provide supplements to 270,000 babies in 100 counties. This year 400,000 babies in 300 counties are meant to get them. Later this year Mr Lu’s charity will begin a tiny pilot of an early-parenting programme, akin to America’s Head Start, in 50 villages, with 50 more villages being used for controlled comparison. James Heckman, an economist and Nobel laureate who has researched early-childhood development, is helping design the study. Such programmes look promising. But they are tiny.

Part of the problem in getting local or provincial governments to spend money on childhood nutrition is that the payoffs are years in the making. And the returns might not go to the village or province, but to cities miles away, in the form of more skilled workers who move there. Central ministries are keen to invest, Mr Lu says, but they want to spend their cash on things that officials crave more than children do—like buildings in villages for each ministry.

For Mr Lu one kind of building does promise a big payoff—village early-education centres, or preschools. His charity has set them up in 677 villages, often using redundant elementary schools. In Songjia village Tian Lin, 22, and her older sister, Tian Hongjiao, teach 26 children aged three to six, including the younger sister’s own three-year-old son. They cook lunch with whatever the children bring from home. Those with migrant-worker parents, who are a bit better off, may have a chunk of pork; others bring a meagre potato or vegetable. Either way all the children get a ying yang bao with their lunch.

In 2012 a study found the anaemia rate among the three- to five-year-olds in this county was close to 18%, more than twice the average for poor rural areas nationwide, according to Mr Lu’s CDRF. He reckons that, on coming to the centres, the children show only 20% of the memory retention of their urban counterparts and 40-60% of their language abilities and cognition. But nutritional supplements help. A study of nine- and ten-year olds, co-written by Mr Rozelle, found that taking a daily chewable vitamin with iron for six months not only cut anaemia levels. It also improved their maths.

pre-school centre in Songjia

pre-school centre in Songjia

Malnutrition Plagues Children of Rural China
China became an economic superpower in only a matter of decades. Forbes Magazine’s annual rich list reported that China has had 152 billionaires this past year. The once struggling nation has shown promising improvement. According to the World Bank, the number of impoverished people living in China dropped from 683 million in 1990 to 157 million in 2009. This improvement is a result of the rapid urbanization in China in recent years. Greater economic opportunity and government assistance is now available in cities. However, children in rural villages are stuck in a seemingly unbreakable cycle of poverty.

The children of rural China face a variety of challenges that are virtually nonexistent in the cities. Among one of the most glaring is the struggle against malnutrition. UNICEF estimates that there are 12.7 million stunted children in China; this life-long condition that results from severe malnutrition plagues children most during early childhood.

stunted due to malnutrition during his first two years of life.

Lttle Han’s elder brother (right) is 9-years-old and stands barely 1.2 meter tall. It is likely that he is stunted due to malnutrition during his first two years of life.

Back home, noodles without beef and porridge are the staple foods. For an average rural family in Hualong, potato is almost their sole source of vegetable.  Beef and mutton are only consumed during rare festive occasions.

Many families cannot afford to keep any sheep or cattle, therefore both milk and meat can be rarely found on the dining table.

“Babies eat the same food as their mothers after breastfeeding stops – we all know there is not enough nutrition for them, but we didn’t know what to do,” said Dr. Wang Chunhua, from the  township hospital,. She has delivered over 500 babies during her 10 years’ service in Hualong.

In addition to malnutrition, anemia takes a tremendous toll on rural Chinese children. Stanford University conducted a test on 1824 babies in China’s Shaanxi Province. Forty nine percent of the babies tested were anemic and 28 percent were near anemic. Furthermore, of all the babies tested, 40 percent displayed cognitive or motor problems.

Why are rates of anemia so high? Stanford reports that while the parents were generally willing to spend additional money on food for their children, they were uninformed on what type of nutritional value the food should have. Many micronutrients, such as iron, were missing, indicating that fresh fruits and vegetables were consumed infrequently. Additionally, further investigation revealed that mothers stopped breastfeeding after six months. From that point on, the child would typically eat rice porridge or soups.

Misinformed parents are often responsible for their children’s poor health. Parents often do not introduce solid food into children’s diets until they are 12 to 18 months old, though it is recommended that solid food make up half of a one-year-old’s diet. Many parents believe myths that babies cannot digest hard foods or that particular foods, like rice, are better for cognitive development.

Treating anemia and replenishing nutrients is actually quite easy. Stanford researchers state that simply taking iron supplements can counter anemia. To address the rampant malnutrition in China’s poor, rural provinces, UNICEF has begun to distribute a nutrition supplement called Ying Yang Bao. Ying Yang Bao is a small packet of powdered vitamins, minerals and proteins that can be mixed into solid foods like porridge.

Many rural Chinese families cannot afford to buy fresh fruits, vegetables and proteins like beef. Dairy products are also expensive and difficult to access. Often, noodles, porridge, rice and starches like potatoes constitute meals. Fortunately, the micronutrients in Ying Yang Bao are easily dissolved in porridges and soups.

UNICEF reports that, between 2008 and 2011, more than 30,000 rural children received Ying Yang Bao. After consumption, anemia levels were cut in half. A long-term solution to malnutrition is still in the works. While aid from UNICEF and other organizations is improving the health of rural children, education is a key issue to be addressed. Parents are misguided by myths and superstitions, which has led to the silent suffering on many children. A public education program has not been officially instituted, but would be another component of China’s long-term solution for malnutrition.

– Bridget Tobin

Child: Care, Health and Development

Volume 31Issue 4pages 417–423July 2005

  • feeding practices;
  • nutrition;
  • rural China


Background  China has the largest population in the world with more than 70% of the people living in rural areas. Over 34% of children under the age of 5 years are responded to show moderate or severe growth stunting, so United Nations International Children’s Emergency Fund and Chinese Ministry of Health conducted this large-scale survey in China. This study aimed to learn the feeding practice, to find the problems in child-feeding practice and to provide evidence for the government to develop an approach to child malnutrition in rural China.

Methods  A structured  questionnaire  was  used  to  survey  21 036  mothers  of  children  with  age  of 0–24 months.

Results  Of the 20 915 children, 98.22% were breastfeeding and 24.36% were exclusively breastfeeding. The proportion of children with weekly protein intake was 78.47%. Among the infants under 4 months, the risk of pneumonia in the group of exclusive breastfeeding was 1.69%, while in the group of non-exclusive breastfeeding was 3.63%, showing a statistically significant difference between the two groups. The risk of diarrhoea in the group of exclusive breastfeeding and in the group of non-exclusive breastfeeding among the infants under 4 months was 24.37% and 40.86%, respectively, also showing a statistically significant difference between the two groups. For children with age 4–6 months, the complementary feeding contributed to a higher prevalence of diarrhoea, but not pneumonia.

Conclusions  The breastfeeding was very common, but the exclusive breastfeeding was quite low and the exclusive breastfeeding for children under the age of 4 months decreased the risks of pneumonia and diarrhoea. For children with age 4–6 months, the exclusive breastfeeding could decrease the risk of diarrhoea, too. Protein intake was insufficient for children in rural China. The rural people lacked health knowledge and were greatly influenced by traditional feeding practices.

Physical growth of children and adolescents in China over the past 35 years

Xin-Nan Zong a & Hui Li a

  1. Department of Growth and Development, Capital Institute of Pediatrics, No. 2 Yabao Road, Chaoyang District, Beijing 100020, China.

Correspondence to Hui Li (email:

(Submitted: 18 June 2013 – Revised version received: 10 December 2013 – Accepted: 14 January 2014 – Published online: 05 June 2014.)

Bulletin of the World Health Organization 2014; 92:555-564. doi:


In 1978, the Government of China introduced economic reforms to convert the country’s planned economy into a free-market system. Since then, sustained economic productivity has greatly increased the food supply, average household income and personal expenditure on food.1,2 With increasing urbanization, the average Chinese diet has become higher in fat and calories, and lower in dietary fibre.3 Also, the level of physical activity during work and leisure time has declined.4In short, dietary changes after these economic reforms have been accompanied by a rise in diseases related to affluence.5,6

Child-growth assessments are useful not only for monitoring a population’s nutritional status, but also for gauging inequalities in human development among different populations.7 Although many growth and nutrition surveys among children and adolescents have been carried out in China,8,9 few have tried to link trends in child growth and nutrition to changes in economic development. One study that evaluated the effects of China’s economic reforms on the growth of children showed an increase in the average height of children in both rural and urban areas. However, the increase in urban areas was five times that of rural areas.10

Since the economic reforms, income inequalities have increased between western rural areas and coastal areas, as well as between and within rural and urban areas.11These inequalities have probably influenced the regional distribution of malnutrition and how this distribution has changed over time.12

The objective of this paper is to give an overall picture of long-term trends in the growth and nutritional status of Chinese children and adolescents by examining the results of seven large surveys conducted over the past 35 years. We focused on regional disparities in child and adolescent growth and nutritional status, as well as on changes in the pattern and rates of malnutrition after the transition to a more high-fat, high-energy-density and low-fibre diet in an attempt to determine if these changes were associated with the country’s economic development.


Data procurement

Growth and nutrition data

Data on the growth and nutritional status of children and adolescents between 0 and 18 years of age were extracted from published data and raw datasets of seven large surveys undertaken in one or more areas with different economic characteristics in China between 1975 and 2010. The following surveys were included: National Growth Survey of Children under 7 years in the Nine Cities of China; National Growth Survey for Rural Children under 7 years in the Ten Provinces of China; National Epidemiological Survey on Simple Obesity in Childhood; Chinese National Survey on Students’ Constitution and Health; China National Nutrition Survey; Chinese Food and Nutrition Surveillance system and China Health and Nutrition Survey. A summary of these surveys can be found in Table 1.

Classification of economic areas was based on five indices: regional gross domestic product (GDP), total yearly income per capita, average food consumption per capita, natural growth rate of population, and the regional social welfare index.8 The areas were categorized from highest to lowest economic status as large coastal cities, high, medium or low cities, high, medium or low rural areas and poor western rural areas.

Economic data

Development indicators for China were obtained from the World Bank;29 GDP per capita, the Gini index and the percentage of the population living in urban areas between 1970 and 2012.

Mortality data

Mortality rates for infants and for children less than 5 years of age between 1990 and 2013 were obtained from the Global Burden of Disease study.30

Dietary data

Dietary data for children and adolescents – daily intake of calories, fats, and protein – were obtained from the China Health and Nutrition Survey24 and the China National Nutrition Survey.20

Sedentary behaviour and physical activity

To describe trends in the level of physical activity, data on sedentary behaviour (hours per day watching television or videos or using the computer) and on passive commuting to and from school were obtained from replies to the China Health and Nutrition Survey questionnaire.25,26

Data analysis

Since the study designs, location and demographic characteristics of the population vary among the surveys, data from subsequent rounds of the same survey were used to assess trends. We assessed undernutrition using data for underweight and stunting. Underweight was defined as less than minus two standard deviations from the median weight-for-age of the reference population. Stunting was defined as less than minus two standard deviations from median height-for-age of the reference population. We assessed obesity using data for both overweight and obesity as defined by the Working Group on Obesity in China, adjusted for each year of age.31

We examined the statistical associations between physical growth and economic development using ecological comparisons and trends. To explore the relationship between height and GDP and urbanization and infant and child mortality rates, we calculated Pearson’s correlation coefficients (r), adjusting for sex. Trends in the prevalence of underweight, stunting, overweight and obesity were assessed using the χ2 test. SPSS version 13.0 (SPSS Inc., Chicago, United States of America) was used for the statistical analyses.


Secular trends in growth

Between 1975 and 2010, the average height of children and adolescents increased steadily, without any tendency to plateau. The largest increment was noted around puberty, particularly among males, e.g. an increase of 11.9 cm in 13-year-old urban boys. The difference in height between the sexes at 18 years of age increased from 10.3 cm to 12.3 cm during this same period.

Body weight increased in both sexes and all age groups from 1985–2010. After 2005, in all age categories boys were heavier than girls (Fig. 1). To assess whether the increase in adolescents’ average height was associated with economic development – as captured by urbanization, GDP per capita and the Gini index – (Fig. 2), we looked for correlations between two of these indicators and the average height of adolescents 17–18 years of age.

Fig. 1. Changes in physical height and body weight of children and adolescents living in Chinese urban areas, 1975–2010

Fig. 1. Changes in physical height and body weight of children and adolescents living in Chinese urban areas, 1975–2010

Fig. 1. Changes in physical height and body weight of children and adolescents living in Chinese urban areas, 1975–2010

Sample size: n = 140 229 aged 0–18 years in 1975; n = 79 194 for children less than 7 years of age in 1985; n = 79 154 for children less than 7 years of age in 1995; n = 69 760 for children less than 7 years of age in 2005; n = 204 973 aged 7–18 years in 1985; n = 105 409 aged 7–18 years in 1995; n = 117 997 aged 7–18 years in 2005 and n = 107 574 aged 7–18 years in 2010.
Data sources: National Growth Survey of Children under 7 years in the Nine Cities of China13 and Chinese National Survey on Students Constitution and Health.32

Fig. 2. Trends in gross domestic product (GDP) per capita, Gini index, urban population and child mortality rate in China, 1975–2010

Height showed a close correlation with GDP

Height showed a close correlation with GDP

US$, United States dollars.
Data sources: GDP, Gini index and urban population from the World Bank;29 infant mortality and under-5 years mortality rates from the World population prospects: the 2010 revision.30

Height showed a close correlation with GDP per capita (r = 0.90, P < 0.0001) and with urbanization (r = 0.92, P < 0.0001). We also looked for a correlation between the decline in infant and under-5 mortality rates (Fig. 2) and average height and observed that they were both negatively correlated (r = −0.95; P < 0.0001), even after sex adjustment (r = −0.94; P < 0.0001).

Geographical disparities

Differences in height were observed in areas having different economic characteristics. Data from the National Growth Survey of Children under 7 years in Nine Cities of China and the National Growth Survey for Rural Children under 7 years in Ten Provinces of China showed that, on average, children of both sexes in rural areas were 2.1 cm (standard deviation, SD: 1.2) shorter than those in suburban areas and 3.6 cm (SD: 2.0) shorter than those in urban areas.

According to the Chinese National Survey on Students’ Constitution and Health, children and adolescents between 7 and 18 years of age who lived in a coastal city were taller, on average, than those living in other provincial capitals. They were also markedly taller, on average, than those living in medium-sized or small cities. Similar differences were observed among rural areas showing high, moderate and poor economic development (Fig. 3).

Fig. 3. Physical heighta in children and adolescents of different economic status groups, China, 2005

National Growth Survey of Children under 7 years in the Nine Cities of China

National Growth Survey of Children under 7 years in the Nine Cities of China

a Height was measured as length for children less than 3 years of age.
Sample size: n = 69 760 urban children less than 7 years of age; n = 69 015 suburban children less than 7 years of age; n = 95 925 rural children less than 7 years of age;n = 81 438 urban children and adolescents aged 7–18 years; n = 111 584 rural children and adolescents aged 7–18 years.
Data sources: National Growth Survey of Children under 7 years in the Nine Cities of China,13 National Growth Survey for Rural Children under 7 years in the Ten Provinces of China9 and Chinese National Survey on Students Constitution and Health.17,18

Trends in malnutrition

The prevalence of undernutrition in children less than 5 years of age was highest in poor rural areas. Compared with the 1990s, the overall prevalence of undernutrition has declined sharply – by 74% for underweight and 70% for stunting. Significant downward trends in the prevalence of both underweight and stunting were observed for all areas (P < 0.001). However, in poor rural areas in 2010, the prevalence of underweight and stunting was still high, at 8.0% and 20.3%, respectively (Fig. 4).

Fig. 4. Trends in underweighta and stuntingb in children less than 5 years of age, China, 1990–2010

below minus two standard deviations from median weight-for-age of the reference population

below minus two standard deviations from median weight-for-age of the reference population

a Underweight was defined as below minus two standard deviations from median weight-for-age of the reference population.
b Stunting was defined as below minus two standard deviations from median height-for-age of the reference population.
Sample size: n = 3200 rural children and n = 1130 urban children in 1990; n = 2139 rural children and n = 765 urban children in 1995; n = 10 729 rural children and n = 5770 urban children in 2000; n = 10 501 rural children and n = 5535 urban children in 2005; n = 10 596 rural children and n = 4803 urban children in 2010.
Data source: Chinese Food and Nutrition Surveillance System.21–23

In 2010, the combined prevalence of overweight and obesity was found to be highest among urban boys (23.2%), followed by rural boys (13.8%), urban girls (12.7%) and rural girls (8.6%). Significant increases were noted in the combined prevalence of overweight and obesity in all groups (P < 0.001) (Fig. 5). Between 1985 and 2010, the proportion of obese males increased faster than that of obese females. In urban areas, male obesity increased 0.34 percentage points per year, compared with 0.15 for female obesity. In rural areas, the increase was 0.18 percentage points per year for male obesity, compared with 0.10 for female obesity. The increase in obesity in urban areas between 1985 and 2000 was twice that of the increase in rural areas during the same time period. However, between 2005 and 2010, the annual increase in obesity in rural areas has outpaced that of urban areas (0.34 versus 0.30 percentage points in males and 0.17 versus 0.10 percentage points in females).

Fig. 6 (not shown) illustrates the burden of obesity in areas with different economic characteristics. Large coastal cities were the first to exhibit a rise in overweight and obesity and had the largest increase in prevalence – 32.6% (males) and 19.1% (females) in 2010. Similar increases followed in other areas: first in large, prosperous cities, followed by medium-sized cities with a large middle class and, finally, by the more affluent rural areas. Although an increase in obesity was noted between 1985 and 2010 in western rural areas with low economic development, these areas still had the lowest prevalence of obesity in 2010.

Trends in nutrition and physical activity

To assess whether factors associated with increased body weight in children and adolescents were affected by China’s economic reforms, we obtained data on fat and protein intake and level of physical activity. Between 1991 and 2009, people’s diets in China changed considerably. For children and adolescents between 7 and 17 years of age, the average daily fat intake increased from 55 to 66 g and the average daily protein intake decreased from 66 to 58 g. There was also an increase in fats as a proportion of total caloric intake and an increase in the proportion of children and adolescents obtaining more than 30% of their energy from fat. In addition, during this period time spent in front of a television, video or computer also increased, as did the proportion of children and adolescents who commuted to school in a motorized vehicle (Fig. 7)(not shown).

The economic transition

In the wake of the 1978 reforms, China underwent many changes in its social structures, living conditions and diet. This has been accompanied by a positive trend in the physical growth of children.33 An empirical division of China’s economic development into stages based on the time cycle of China growth surveys facilitates the analysis of its association with trends in children’s growth. In Stage I (before 1975) – out of scope of this analysis – a previous subtle upward trend in growth ceased and even reversed owing to the detrimental effects of famine. In Stage II (1975–1985), children’s growth began to improve again with the recovery of the national economy, and positive trends emerged in older age groups of children in the major cities. In Stage III (1985–1995), physical growth continued to improve in parallel with sustained economic growth. The increment in height among children in rural areas exceeded that seen in children living in urban areas because of improved living standards, health care and increased food supply in the rural areas in the mid-1980s.9 In Stage IV (1995–2005), even higher growth increments were documented among both urban and rural residents. According to data from 2005 to 2010 (Stage V), the increment has continued and does not seem to be levelling off.34

The growth of children in China has improved in recent decades and this improvement is more pronounced at puberty than at earlier or later ages, consistent with other population-based studies.35 The increase in height at the age of 18 years is already present in younger ages and the eventual increase in adult height is established during the first 2 years of life.

In the Netherlands, the secular increase in growth has come to a halt after 150 years, with males now 13.1 cm taller on average than females.36 Since sex difference in adult height widens gradually as secular increases in growth continue, the difference of 12.3 cm between the sexes in 2010 suggests that the positive trend in Chinese children may continue.

Before the economic reforms, food had been in short supply,3 but after 1978, when a policy of liberal food production was introduced and annual economic growth improved, people began to eat more meat and grains and less vegetables. Child growth and nutrition improved and overweight and obesity were still rare. In 1985 and 1986, the prevalence of obesity in children and adolescents was below 1% in large cities.15,19

In 1986, China started its first specific survey on obesity and found that the Chinese diet had become richer in fats and calories and lower in fibre, a change that was introducing an increased risk of chronic diseases.37,38 Obesity among infants and preschool children increased by a factor of 2.8 between 1986 and 2006.15 And between 1985 and 2010, overweight among school-aged children and adolescents increased from 1.11% to 9.62% and obesity from 0.13% to 4.95%.16 Additionally, between 1993 and 2009 the prevalence of obesity rose from 6.1% to 13.1% among children between the ages of 6 and 17 years.39 The higher prevalence of overweight males contrasts with the situation in some non-Asian countries.40

In 2012, for the first time in history, China’s urban population outnumbered its rural population.41 This urbanization can be seen as a double-edged sword. Although it has brought increased access to health care and improvements in basic health infrastructure for many, it has also brought about changes in diet and lifestyle, such as an increase in the availability of sweets and fast-food restaurants and in the use of television, personal computers and cars, all of which can pose substantial health risks.42,43

We have shown that in recent decades fat intake and physical inactivity have risen among Chinese children, with a resulting increase in childhood obesity and a documented decline in physical fitness. For instance, the capacity for endurance running among Chinese students declined significantly between 1985 and 2010.32,44

Dual burden of malnutrition

Large discrepancies still exist between rural and urban areas both in health conditions and in health care.45 Decades of observation suggest that despite improved growth in children belonging to all economic groups, a large growth disparity persists between the rural and suburban areas and the urban areas,9 and among different economic subgroups within these areas.17,18

Compared with the late 1980s and early 1990s,46 in 2010, malnutrition in childhood declined dramatically, owing to sustained economic development, sound nutrition policies, improved health services for women and children and broad implementation of child nutritional interventions.23 However, in the same year, nutrition in rural areas was still poor, with a high prevalence of underweight and stunting among children less than5 years of age. Another survey in 2009 reported 15.9% prevalence for stunting, 7.8% for underweight and 3.7% for wasting in poor rural ares.47

We have also observed a paradoxical situation: in 2006, prevalence of overweight children was as high as 16.8%, while that of stunting was 57.6% among the children in the same poor areas of China’s midwestern provinces.48 The coexistence of stunting and overweight in the same child is a result of protein and energy malnutrition, which retards height despite increased body weight,49 and Chinese rural children have a lower daily protein intake than urban children.24

Childhood obesity has become a serious public health problem in China.19,50 The current strategies for preventing and controlling malnutrition need to be re-examined. Research on obesity prevention and control needs to be improved and nutrition policies need to be aligned with appropriate obesity prevention strategies. Cross-sectoral collaboration such as between health and agriculture, needs to be promoted.

Our study has shown that regional inequalities in child growth and nutrition in China accompany regional economic disparities. Therefore, to promote equitable growth for all children in China, strategies for optimal nutrition need to focus more closely on disadvantaged groups in the poor and underdeveloped areas.


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  4. Qin L, Stolk RP, Corpeleijn E. Motorized transportation, social status, and adiposity: the China Health and Nutrition Survey. Am J Prev Med. 2012;43(1):1–10. pmid: 22704739
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  7. de Onis M, Frongillo EA, Blössner M. Is malnutrition declining? An analysis of changes in levels of child malnutrition since 1980. Bull World Health Organ. 2000;78(10):1222–33. pmid: 11100617
  8. Ji CY, Chen TJ. Secular changes in stature and body mass index for Chinese youth in sixteen major cities, 1950s-2005. Am J Hum Biol. 2008;20(5):530–7. pmid: 18478539
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  10. Shen T, Habicht JP, Chang Y. Effect of economic reforms on child growth in urban and rural areas of China. N Engl J Med. 1996;335(6):400–6. pmid: 8663882
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listless child who was among many kwashiorkor cases

listless child who was among many kwashiorkor cases

This late 1960s photograph shows a seated, listless child who was among many kwashiorkor cases found in Nigerian relief camps during the Nigerian-Biafran war. Kwashiorkor is a disease brought on due to a severe dietary protein deficiency, and this child, whose diet fit such a deficiency profile, presented with symptoms including edema of legs and feet, light-colored, thinning hair, anemia, a pot-belly, and shiny skin. Image courtesy of Dr. Lyle Conrad and the CDC Public Health Image Library.



Even where children get the calories they need—as most do in rural China—they are not being fed the right things. In one study of 1,800 infants in rural Shaanxi province in China’s north-west, 49% were anemic and 40% were significantly hampered in developing either cognitive or motor skills. Fewer than one in ten were stunted or wasting, meaning that in most cases the problem was not lack of calories, but lack of micronutrients.

Part of the problem in getting local or provincial governments to spend money on childhood nutrition is that the payoffs are years in the making. And the returns might not go to the village or province, but to cities miles away, in the form of more skilled workers who move there. Central ministries are keen to invest, Mr Lu says, but they want to spend their cash on things that officials crave more than children do—like buildings in villages for each ministry.

For Mr Lu one kind of building does promise a big payoff—village early-education centres, or preschools. His charity has set them up in 677 villages, often using redundant elementary schools. In Songjia village Tian Lin, 22, and her older sister, Tian Hongjiao, teach 26 children aged three to six, including the younger sister’s own three-year-old son. They cook lunch with whatever the children bring from home. Those with migrant-worker parents, who are a bit better off, may have a chunk of pork; others bring a meagre potato or vegetable. Either way all the children get a ying yang bao with their lunch.

In 2012 a study found the anemia rate among the three- to five-year-olds in this county was close to 18%, more than twice the average for poor rural areas nationwide, according to Mr Lu’s CDRF. He reckons that, on coming to the centres, the children show only 20% of the memory retention of their urban counterparts and 40-60% of their language abilities and cognition. But nutritional supplements help. A study of nine- and ten-year olds, co-written by Mr Rozelle, found that taking a daily chewable vitamin with iron for six months not only cut anaemia levels. It also improved their maths.

children under the age of five, wasting and stunting

children under the age of five, wasting and stunting

Despite progress, malnutrition remains a challenge

AKARTA, 30 August 2012 (IRIN) – While Indonesia in relative terms is cutting the number of malnourished children under the age of five, wasting and stunting – especially in certain pockets of the country – remain a major concern, say health experts.



Vitamin A deficiency

A few salient facts

  • An estimated 250 million preschool children are vitamin A deficient and it is likely that in vitamin A deficient areas a substantial proportion of pregnant women is vitamin A deficient.
  • An estimated 250 000 to 500 000 vitamin A-deficient children become blind every year, half of them dying within 12 months of losing their sight.

A collateral challenge

Vitamin A deficiency (VAD) is the leading cause of preventable blindness in children and increases the risk of disease and death from severe infections. In pregnant women VAD causes night blindness and may increase the risk of maternal mortality.

Vitamin A deficiency is a public health problem in more than half of all countries, especially in Africa and South-East Asia, hitting hardest young children and pregnant women in low-income countries.

Crucial for maternal and child survival, supplying adequate vitamin A in high-risk areas can significantly reduce mortality. Conversely, its absence causes a needlessly high risk of disease and death.

  • For children, lack of vitamin A causes severe visual impairment and blindness, and significantly increases the risk of severe illness, and even death, from such common childhood infections as diarrhoeal disease and measles.
  • For pregnant women in high-risk areas, vitamin A deficiency occurs especially during the last trimester when demand by both the unborn child and the mother is highest. The mother’s deficiency is demonstrated by the high prevalence of night blindness during this period. The impact of VAD on mother-to-child HIV transmission needs further investigation.

The most damaging micronutrient deficiencies in the world are the consequence of low dietary intake of iron, vitamin A, iodine and zinc. Vitamin A deficiency (VAD) is prevalent among the poor whose diets are based mainly on rice or other carbohydrate-rich, micronutrient-poor calory sources. Rice does not contain any β-carotene (provitamin A), which their body could then convert into vitamin A. Dependence on rice as the predominant food source, therefore, necessarily leads to VAD, most severely affecting small children and pregnant women. In 2012 the World Health Organization reported that about 250 million preschool children are affected by VAD, and that providing those children with vitamin A could prevent about a third of all under-five deaths, which amounts to up to 2.7 million children that could be saved from dying unnecessarily.

VAD compromises the immune systems of approximately 40 percent of children under five in the developing world, greatly increasing the severeness of common childhood infections, often leading to deadly outcomes. VAD is most severe in Southeast Asia and Africa. For the 400 million rice-consuming poor, the medical consequences are fatal: impaired vision—, in extreme cases irreversible blindness; impaired epithelial integrity, exposing the affected individuals to infections; reduced immune response; impaired haemopoiesis (and hence reduced capacity to transport oxygen in the blood) and skeletal growth; among other debilitating afflictions.

Rice containing provitamin A could substantially reduce the problems described above. This can only be achieved using genetic engineering because there is no provitamin A in the rice seeds, even though it is present in the leaves. Thousands of rice varieties have been screened for this trait without success. Existing coloured rice varieties contain pigments that belong to a different chemical class.

Small children are most susceptible to micronutrient deficiencies. Initially a VAD affects their eyesight, but at the same time it impairs their immune system, and children fall prey to common infectious diseases. Vitamin A and zinc alone could save more thn a third of the 12 million children who die annually because of malnutrition worldwide.

Golden Rice has the potential to complement existing efforts that seek to reduce blindness and other VAD induced diseases. Those efforts include industrial fortification of basic foodstuffs with vitamin A, distribution of vitamin supplements, and increasing consumption of other foods rich in vitamin A.

Distribution of Vitamin A Deficiency (WHO, 2009)

Distribution of Vitamin A Deficiency (WHO, 2009)


Black, Robert E, Cesar G Victora, Susan P Walker, Zulfiqar A Bhutta, Parul Christian, Mercedes de Onis, Majid Ezzati, Sally Grantham-McGregor, Joanne Katz, Reynaldo Martorell, Ricardo Uauy, the Maternal and Child Nutrition Study Group. 2013. “Maternal and child undernutrition and overweight in low-income and middle-income countries. “Lancet Volume 382, No. 9890, p 427–451.  (The article is available free of charge, but you will be required to register with Lancet.)

Black RE, Morris SS, Bryce J. “Where and why are 10 million children dying every year?”Lancet. 2003 Jun 28;361(9376):2226-34.

Black, Robert E, Lindsay H Allen, Zulfiqar A Bhutta, Laura E Caulfield, Mercedes de Onis, Majid Ezzati, Colin Mathers, Juan Rivera, for the Maternal and Child Undernutrition Study Group Maternal and child undernutrition: global and regional exposures and health consequences. (Article access is free but will require registration) The Lancet  Vol. 371, Issue 9608, 19 January 2008, 243-260.

Jennifer Bryce, Cynthia Boschi-Pinto, Kenji Shibuya, Robert E. Black, and the WHO Child Health Epidemiology Reference Group. 2005. “WHO estimates of the causes of death in children.” Lancet ; 365: 1147–52.

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Food and Agriculture Organization. 2012. FAO Statistical Yearbook 2012

Food and Agriculture Organization, International Fund for Agricultural Development, World Food Program. 2014. “The State of Food Insecurity in the World 2014. Strengthening the enabling environment for food security and nutrition.”  Rome: FAO

Institute of Development Studies. “Hunger and Nutrition Commitment Index.”  Accessed March 2015.

International Food Policy Research Institute. 2014a. 2014 Global Food Policy Report

International Food Policy Research Institute. 2014b. 2014 Global Hunger Index

Oxford University Press. 1971. Oxford English Dictionary. Definition for malnutrition.

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Rosen, Stacey, Birgit Meade, Keith Fuglie, and Nicholas Rada. 2014.  International Food Security Assessment, 2014-24.  Economic Research Service, United States Department of Agriculture.

UNHCR 2014 “Mid-Year Trends” June 2014.

UNICEF, WHO, The World Bank. 2014a. “Levels and Trends in Child Malnutrition.”

UNICEF-WHO-The World Bank. 2014b “Summary of key facts about the 2013 joint malnutrition estimates.”

Cesar G Victora, Linda Adair, Caroline Fall, Pedro C Hallal, Reynaldo Martorell, Linda Richter, and Harshpal Singh Sachdev. 2008. “Maternal and child undernutrition: consequences for adult health and human capital.” Lancet. 2008 Jan 26; 371(9609): 340–357.

World Bank. 2015. Poverty website. and the Overview page Accessed March 2015.

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World Health Organization.  “Micronutrient Deficiencies.”  Accessed March 2015.


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The matter of stunting in the Ganges Plains

Larry H. Bernstein, MD, FCAP, Curator


Nicholas Kristof wrote had an excellent Op-Ed in the Oct 15, 2015 NY Times.  There is some relevant background on tranthyretin and protein-energy malnutrition that I have previously posted relevant to the discussion, and there are also specific religious beliefs as well as climate change and pollution factors that can’t be ignored.

Water and Climate in the Himalayas

The mountainous states of India, and the nations of Nepal and Bhutan share one of the world’s greatest freshwater resources — water from the snows of the Himalayas and the monsoons which the mountains create. More than 1.4 billion people depend on water from the rivers of the Himalaya, with the eastern rivers like the Ganges much more dependent on rain and groundwater than on direct flow from glaciers. Glacier melt is only 4 percent of the annual 220,000 billion cubic meters of flow for the rivers of Nepal, which feed the Ganges, as estimated in a recent report. One of these rivers is the Trisuli, in this photograph flowing down past Betrawati from the Langtang region of central Nepal.

On a recent journey to Uttarakhand, India, and Nepal, with support from the Karuna Foundation US, the use of water and its abundance, scarcity and quality as our climate changes was crucial everywhere we went. The photos and research presented here were made through the gracious cooperation of the Uttarakhand Environmental Education Center (UEEC), World Wildlife Fund – Nepal (WWF), and The Mountain Institute. Additional information is from International Centre for Integrated Mountain Development (ICIMOD) reports, other NGOs and press reports.

Water flowing down from the Himalaya is mostly abused and polluted as it flows through the cities, even though the water is needed for human use. In Kathmandu, rivers like the Bagmati and its tributary the Vishnumati (also called Bishnumati), seen here, are public and industrial dumps of every kind of waste, despite frequent public awareness campaigns and periodic clean up attempts. As the Nepal Times put it, “The Bagmati River is an open sewer.” Nevertheless, people use the water for washing, household use, rituals, and for funeral ceremonies at ghats, including at the holy Hindu temple of Pashupati. The Bagmati is a snow- and rain-fed, not glacial river, and the Vishnumati, only 18 km long, is entirely supplied by rain and groundwater.

Nepal is extremely rich with water, with more than 6,000 rivers and the rains of the monsoon. Yet, according to a report by the International Water Management Institute, more than a quarter of the 29 million population has no access to safe drinking water and “little consideration is given to environmental requirements.” In the Himalayan foothills, where rivers and groundwater are much less polluted than in the cities and valley, seasonal water shortages and lack of safe in-home water supply nevertheless affect most people. We saw families and mothers stooped over to fill bottles, jugs and pans with water leaking from pipes that were snaking down dirt streets in the village of Kalikistan, Rusuwa, Nepal. The pipes supply the village of Jibjibe, but leaks spurted and dripped along the 2 km route, part of which was temporarily suspended across a raw landslide scar (see the Landslides photo set for more about this).

Gesturing broadly up to the surrounding mountains, primary school teacher Dessli Rai of the village of Torke Maimajhuwa, Nepal, tells us there are now no long-lasting snows after winter and thus much less water in the spring pre-monsoon season. The 50-year-old said the change has been noticeable for more than a decade but seems to be increasing. Small streams flowing down from the hills in this area north of Ilam now are drying up, “completely finished, day by day,” in March instead of flowing for two more months. His observations were commonly repeated by others we met in the region: It used to snow heavily at around 2400 m and below, up to a meter in depth and the snow would remain to provide meltwater over several months. In the neighboring Indian state of Uttarakhand, “it never snows in Almora anymore,” said Anuradha Pande of the UEEC. Recent studies reported by ICIMOD found that it has not snowed in Almora, eleveation 1600 m, for 3 to four years and that the lack of snow at medium elevation locations removed “an important source of water for agriculture.” Farmers reported “delayed and erratic rainfall during the rainy season followed by prolonged dry periods.”

In the dawn, four women carry water containers from a spring into the village of Chausali, near Almora, Uttarakhand, India. Women are particularly affected by climate changes due to their daily work which includes getting water, collecting forest wood and fodder, and working in dangerous landslide areas near villages. Researchers of the Indi-German Environment Programme found that, “In the fragile ecological zone in the hilly areas of Uttarakhand, human activities, including agriculture, cause extensive land degradation which, in turn, adversely affect water retention and recharge. The problem of water shortage, exacerbated by extreme weather events such as erratic rainfall, cloudbursts, unpredictable temperatures, etc. leads to detrimental effects on agriculture, forestry” and even manufacturing.

More than 15 women wait as a very slow flow from another spring in Chausali, India, fills their water containers. Several springs in this area have dried up, causing the community to change the traditional division among castes. Women here are limited to filling one container a day. Previously different castes used separate springs, but now upper and lower castes are using the same water sources. Across similar Himalayan foothills areas, inhabitants told ICIMOD researchers in 2011 that local drinking water sources seemed to be drying up; and “on average, they reported a 50 percent decrease in drinking water sources.”

The last of the water from a cistern in Chausali village is drawn up by Bhem Singh Latwal and his wife Kamla Latwal in early March — a time when late winter rains would be expected to have at least partially refilled the underground tank. But in recent years winter rain is scarce, they said. This cistern, fed from rain falling on roofs of the family buildings, was built in 1952 to supply livestock and irrigate the garden. Recent aid from the Indo-German Environment Program through UEEC in the Almora area has helped build new water-conservation facilities like erosion control dams, rooftop rainwater harvesting systems, rejuvenation of springs and catchment areas. The goals of this and other UEEC work include increased availability of drinking and agricultural water, increased soil moisture, and reduced health impacts of drought.

Throughout the Himalayas, most people in villages do not have piped in water but must rely for household use on public roadside taps from springs or catchments. Many community water sources are drying up in the foothills and mountainous regions of Nepal at the same time that regional temperatures are rising at a rapid rate. Studies published in 2011 showed that the “region is one of the world’s hotspots in terms of warming trends.” An ICIMOD report on water in the Himalaya said that the mean maximum temperature in Nepal increased by 0.06 degrees C per year between 1977 and 2000 — equivalent to more than a degree F per decade. In Nepal just as in India, there are already signs of changes in the dates of the onset and retreat of the monsoon as well as the number and frequency of extreme precipitation events, according to scientific research published by ICIMOD.

In the Nepalese village of Jibjibe, a Village Development Committee of Rasuwa District, the family and neighbors of farmer Bhawanath Paudel fill a hand-dug water storage pond. Jibjibe is a village of about 4,000 people which like many mountain hamlets spreads down a steep hillside notched by agricultural terraces above the Phalankhu River. Over the years the townspeople have dealt with uncertain water supplies by building three reservoirs, the water from which runs down past houses in small pipes but is rationed during droughts. When water is flowing, farmers irrigate their vegetable crops like onions, peas, tomatoes, mustard and cabbage and fill small ponds to save the water. Locally-run programs in farmer education, climate change education, and water management have advanced with advice and encouragement of the World Wildlife Fund.

The Ganga’s main stem and tributaries drain more than one million square kilometers of China, Nepal, India and Bangladesh. The Ganga basin in India, which includes the Yamuna sub-basin, covers one fourth of India’s geographical area. From the confluences of the Bhagirathi and the Alaknanda tributaries in the Himalayas, the river Ganga gains additional flow from Nepal’s tributaries, glacial snowmelt and monsoon rainfall. Now the basin’s sediment loads, which are integral to the river system, are driven by the deforestation of the Gangetic plains and construction across the Himalayan regions. For at least two and a half millennia, the river Ganga has nourished human civilizations and great dynasties, and Hindu and Buddhist pilgrimage places have grown up along the riverbanks. By the 4th century BCE, Pataliputra (now near Patna, the capital of the state of Bihar) was one of ten ancient capital cities of India. At the headwaters of the Ganga in the Himalayas, sacred shrines at Gangotri, Kedarnath and Badrinath establish the sources of the river’s sacred power in the Hindu traditions. The temples of Kedarnath and Badrinath rest at the snouts of Himalayan glaciers. Farther downstream in the sacred towns of Uttarkashi and Rishikesh and along the plains at Haridwar, Allahabad (Prayag), Banaras, Vindhyachal, Nadia and Kalighat people worship Ganga’s waters through rituals of purification. The Ganga has been worshipped as a river goddess by Hindus across India and the world. According to the Hindu view, sacred spaces are not detached from ecology and the built environment but are embedded in them; Hindu texts and rituals explain this conjunction of divine power and the physical world. In this integrated view, Ganga is a goddess who absolves worldly impurities and rejuvenates the cosmos with her purificatory power. She is also a mother who cleans up human sin and mess with loving forgiveness. Hindus show their respect to her in oil lamp rituals (arati) performed on the riverbank and in temple worship (puja). Most importantly, devotees seek spiritual purification by doing ritual ablutions (snan) in the river.

Today more than 800 million people reside in the Ganga basin. From the Himalayas to the Bay of Bengal, the Ganga passes by more than 30 major cities of 300,000 or more residents and borders many smaller towns and agricultural tracts. The Ganga provides municipal and industrial water for these cities and they return polluted wastewater to the river system in great quantities.(see Central Pollution Control Board The Upper Ganga plain in the state of Uttar Pradesh is home to sugar factories, leather tanneries, textile industries of cotton, wool, jute and silk, food processing industries related with rice, dal and edible oils, paper and pulp industries, heavy chemical factories, and fertilizer and rubber manufacturing units. Industrial wastewater is discharged by all these industries and contains hazardous chemicals and pathogens. Four major thermal power plants depend upon water from the Ganga.

Water quality in river streams affects and is also affected by ground water tables that are depleted by over-pumping for agriculture. When surface water is polluted and rendered unusable for human purposes, residents turn to groundwater for domestic, municipal, agricultural and industrial needs and this leads to further depletion. The groundwater supply also needs to be recharged by river flows. When hydroelectric dams and canals divert water to needy urban centers they affect this recharge rate. In the warming climate, more rapid and extensive glacial melt may bring more water into the river system at some times of the year but this increase in volume and change in the timing of melting can lead to flash floods especially in riverbeds that have become disembedded from ecological and hydrological systems by dams and diversions. Increased rainfall and glacial melt may help to recharge groundwater and dilute river pollution but they may also lead to dangerous and deadly flooding.

J Environ Qual. 2001 Mar-Apr;30(2):356-68.

Effect on water resources from upstream water diversion in the Ganges basin.

Adel MM1.

Author information


Bangladesh faces at least 30 upstream water diversion constructions of which Farakka Barrage is the major one. The effects of Farakka Barrage on water resources, socioeconomy, and culture have been investigated downstream in the basins of the Ganges and its distributaries. A diversion of up to 60% of the Ganges water over 25 yr has caused (i) reduction of water in surface water resources, (ii) increased dependence on ground water, (iii) destruction of the breeding and raising grounds for 109 species of Gangetic fishes and other aquatic species and amphibians, (iv) increased malnutrition, (v) deficiency in soil organic matter content, (vi) change in the agricultural practices, (vii) eradication of inland navigable routes, (viii) outbreak of waterborne diseases, (ix) loss of professions, and (x) obstruction to religious observances and pastimes. Further, arsenopyrites buried in the prebarrage water table have come in contact with air and formed water-soluble compounds of arsenic. Inadequate recharging of ground water hinders the natural cleansing of arsenic, and threatens about 75,000,000 lives who are likely to use water contaminated with up to 2 mg/L of arsenic. Furthermore, the depletion of surface water resources has caused environmental heating and cooling effects. Apart from these effects, sudden releases of water by the barrage during the flood season cause devestating floods. In consideration of such a heavy toll for the areas downstream, strict international rules have to be laid down to preserve the riparian ecosystems.

Environ Int. 2006 Aug;32(6):831-49. Epub 2006 Jun 16.

Ecological and toxicological effects of inorganic nitrogen pollution in aquatic ecosystems: A global assessment.

Camargo JA1Alonso A.

Author information


We provide a global assessment, with detailed multi-scale data, of the ecological and toxicological effects generated by inorganic nitrogen pollution in aquatic ecosystems. Our synthesis of the published scientific literature shows three major environmental problems: (1) it can increase the concentration of hydrogen ions in freshwater ecosystems without much acid-neutralizing capacity, resulting in acidification of those systems; (2) it can stimulate or enhance the development, maintenance and proliferation of primary producers, resulting in eutrophication of aquatic ecosystems; (3) it can reach toxic levels that impair the ability of aquatic animals to survive, grow and reproduce. Inorganic nitrogen pollution of ground and surface waters can also induce adverse effects on human health and economy. Because reductions in SO2 emissions have reduced the atmospheric deposition of H2SO4 across large portions of North America and Europe, while emissions of NOx have gone unchecked, HNO3 is now playing an increasing role in the acidification of freshwater ecosystems. This acidification process has caused several adverse effects on primary and secondary producers, with significant biotic impoverishments, particularly concerning invertebrates and fishes, in many atmospherically acidified lakes and streams. The cultural eutrophication of freshwater, estuarine, and coastal marine ecosystems can cause ecological and toxicological effects that are either directly or indirectly related to the proliferation of primary producers. Extensive kills of both invertebrates and fishes are probably the most dramatic manifestation of hypoxia (or anoxia) in eutrophic and hypereutrophic aquatic ecosystems with low water turnover rates. The decline in dissolved oxygen concentrations can also promote the formation of reduced compounds, such as hydrogen sulphide, resulting in higher adverse (toxic) effects on aquatic animals. Additionally, the occurrence of toxic algae can significantly contribute to the extensive kills of aquatic animals. Cyanobacteria, dinoflagellates and diatoms appear to be major responsible that may be stimulated by inorganic nitrogen pollution. Among the different inorganic nitrogenous compounds (NH4+, NH3, NO2-, HNO2NO3-) that aquatic animals can take up directly from the ambient water, unionized ammonia is the most toxic, while ammonium and nitrate ions are the least toxic. In general, seawater animals seem to be more tolerant to the toxicity of inorganic nitrogenous compounds than freshwater animals, probably because of the ameliorating effect of water salinity (sodium, chloride, calcium and other ions) on the tolerance of aquatic animals. Ingested nitrites and nitrates from polluted drinking waters can induce methemoglobinemia in humans, particularly in young infants, by blocking the oxygen-carrying capacity of hemoglobin. Ingested nitrites and nitrates also have a potential role in developing cancers of the digestive tract through their contribution to the formation of nitrosamines. In addition, some scientific evidences suggest that ingested nitrites and nitrates might result in mutagenicity, teratogenicity and birth defects, contribute to the risks of non-Hodgkin’s lymphoma and bladder and ovarian cancers, play a role in the etiology of insulin-dependent diabetes mellitus and in the development of thyroid hypertrophy, or cause spontaneous abortions and respiratory tract infections. Indirect health hazards can occur as a consequence of algal toxins, causing nausea, vomiting, diarrhoea, pneumonia, gastroenteritis, hepatoenteritis, muscular cramps, and several poisoning syndromes (paralytic shellfish poisoning, neurotoxic shellfish poisoning, amnesic shellfish poisoning). Other indirect health hazards can also come from the potential relationship between inorganic nitrogen pollution and human infectious diseases (malaria, cholera). Human sickness and death, extensive kills of aquatic animals, and other negative effects, can have elevated costs on human economy, with the recreation and tourism industry suffering the most important economic impacts, at least locally. It is concluded that levels of total nitrogen lower than 0.5-1.0 mg TN/L could prevent aquatic ecosystems (excluding those ecosystems with naturally high N levels) from developing acidification and eutrophication, at least by inorganic nitrogen pollution. Those relatively low TN levels could also protect aquatic animals against the toxicity of inorganic nitrogenous compounds since, in the absence of eutrophication, surface waters usually present relatively high concentrations of dissolved oxygen, most inorganic reactive nitrogen being in the form of nitrate. Additionally, human health and economy would be safer from the adverse effects of inorganic nitrogen pollution.

Dirty Water

India and China share a grave environmental problem—extreme water pollution


The hazy dawn knits river to sky on the banks of the holy Ganges river in Varanasi. Even at sunrise, the city’s 4.5-mile waterfront bustles. Bathers brush their teeth, soap themselves, and scrub their children. Legions wash laundry, gather water, and scour dishes. Men swim and lounge on ghats (steps that descend into the Ganges). Black noses and curving horns betray the presence of submerged water buffalo.

Women in bright saris gather in groups or with their families at the water’s edge. Up to 60,000 pilgrims journey to this sacred, 3,000-year-old city from across India each day. They sculpt altars in slick, gray mud, making offerings of flowers and candles. They pour Ganges water, pray, take a sacramental sip and immerse themselves in the turbid river for spiritual healing.

At the “burning ghats,” flames consume the bodies of the dead: Hindus believe casting their remains into the Ganges guides their souls to heaven. To them, this river is the mother goddess, Ganga Ma, who washes away humanity’s sins.

Four hundred million people rely on the Ganges watershed for drinking water, including Varanasi’s 1.6 million residents. But along its 1,560-mile journey from the Himalayas to the Bay of Bengal, the river absorbs raw sewage from 116 cities. Waste has turned these waters into a highway for viruses and bacteria, including deadly, dysentery-causing microbes like E. coli O157 and Shigella, and those that cause cholera, hepatitis A, and typhoid fever. Last year, the Indian government pledged $4 billion for river cleanup to stem the tide of waterborne disease.

But the problem of environmental water pollution extends far beyond the Ganges. Municipal waste, pesticides, and industrial chemicals foul waterways and drinking water across the globe, with the worst pollution concentrated in developing countries. If India’s waterways are the dubious poster children for sewage, then China’s waters take that role for toxic chemicals. Municipal waste is also a severe problem in China, but three decades of meteoric industrial growth have laced lakes and rivers with a witches’ brew of chemicals. Some Chinese waters are now among the most polluted on Earth.

There are few statistics on global health impacts from waterborne chemical exposures, but there is data on fecal contamination. Diarrhea is the second-largest killer of children under five, causing about 1.5 million deaths annually, says Eric Mintz, an epidemiologist at the U.S. Centers for Disease Control and Prevention. India tops that list. Mintz notes that the younger the child, the greater their risk of life-threatening dehydration. Unsafe drinking water, sanitation, and poor hygiene are almost always to blame. In 2006, nearly one billion people lacked access to “improved” drinking water (from a municipal water supply or a deep-dug well), according to the World Health Organization (WHO). Another 2.5 billion lived in homes without a toilet.

Problems on a holy river
Year round, children stream through the emergency room at Varanasi’s Sir Sundar Lal Hospital with illnesses that can be directly attributed to use of contaminated water, says Dr. Ashok Kumar, a pediatrician. They are treated—and quickly re-infected. “As a result, most of these children also have concomitant malnutrition, which further weakens their immunity and makes them vulnerable to more frequent and severe episodes of diarrhea,” he says. They also carry waterborne intestinal parasites like cryptosporidium and giardia, which further stunt their growth and development. For many families, costs are prohibitive, so children don’t get proper medical care—or come too late.

One of the Ganges’s most vocal protectors is Veer Bhadra Mishra, a 70-year-old Brahmin civil engineer and priest of Varanasi’s second-largest temple. In 1982, he founded the Sankat Mochan Foundation (SMF; Sankat Mochan means “deliverer from troubles”) with colleagues from Banaras Hindu University. Their goal was to foster awareness about the causes of Ganges pollution—and to act as guardians, technical advisers and activists to spark river cleanup.

Varanasi generates over 80 million gallons of sewage daily. “The whole city’s nightsoil is coming to the river,” says Mishra. Output continues to rise with the burgeoning population and many of the 33 outflows along the city waterfront are adjacent to the busiest ghats. “If public health is the issue, point-source pollution from untreated sewage is over 90 percent of the problem,” he says.

A lab run by SMF has monitored river water quality since 1993. Downriver, concentrations of bacteria that indicate fecal contamination sometimes top 1.5 million in a 100-milliliter test tube of water. In the U.S., beaches are closed when concentrations reach 200.

Sarai Mohana, one of many “unplanned villages” downstream, is ground zero for Varanasi’s sewage crisis. It lies at the confluence of the Varuna River, where black, stinking water pours into the Ganges and methane bubbles rise from the sediment. No pilgrims come here: the village is home to some of Varanasi’s poorest citizens and the river is utilitarian. Makeshift housing and crop fields dot the shoreline where cows and buffaloes graze or bathe. Fishermen cast their nets nearby, one of them, 35-year-old Nakharu Sahani lives in Sarai Mohana. His family eats fish every day, but they don’t drink from the Ganges. “How could we drink this water?” he asks.

He and other residents lack both sewerage and a piped, treated drinking water supply. They draw foul-smelling, discolored water that sometimes squirms with thread-like worms from hand-pumped wells.

Sarai Mohana was included in the only published study on public use of the Ganges and health. Steve Hamner, a microbiologist from Montana State University, interviewed 104 families at four locations along the river in 2004. “Though it was a small sampling, this study demonstrated a very high incidence of waterborne disease,” he says.

Socio-economic factors influence infection rates. At more affluent sites upstream where people have indoor plumbing, the waterborne illness rate over the previous year was 38 percent. Sarai Mohana had a 90 percent illness rate.

Moves toward cleanup
Mishra has been trying to bring cheap, algae-based sewage treatment to India since 1994. This “advanced integrated wastewater pond system” (AIWPS), developed by University of California Berkeley engineers William Oswald and Bailey Green, has been used in California for 44 years. Treated water meets stringent state standards for irrigation, discharge into a river, or for processing into clean drinking water.

Over 45 days, sewage cycles through an engineered natural system that mimics how nature deals with waste, says Green. In a series of four ponds, bacteria, algae, and sunlight ferment and break down sludge and purify the water, removing 99.999 percent of fecal coliform bacteria.

In February 2009, Prime Minister Manmohan Singh named Ganges cleanup a nation-wide priority, creating the new National Ganga River Basin Authority. The government committed $4 billion to stop the flow of waste into the Ganges by 2020, including a $1 billion World Bank loan. Some of that money will explore alternative technologies. Funding has been approved for a small-scale demonstration AIWPS plant capable of handling 10 million gallons of waste per day. Green’s company, California-based GO2 Water, Inc., and SMF submitted a detailed project design to the government in February. The plant could be up and running by 2011, Green says.

If approved, it would take another five years to design and build a second, larger AIWPS plant just below the city. This energy-efficient plant will be fed by a new sealed, gravity-driven interceptor sewer system that flows downhill, requiring less electricity. It could handle the entire city’s sewage flow.

In 1985, Mishra’s battle to clean up the Ganges helped attract the attention of Rajiv Gandhi, who launched the Ganga Action Plan (GAP). As part of that initiative, the government built a traditional wastewater treatment for Varanasi using what Green considers “conventional, energy-intensive technology developed for cold climates.” The system is ill-suited to the tropics: it requires continuous electricity in a country plagued by constant outages—and when monsoon rains overwhelm pumping stations, sewage never reaches the treatment facility and gushes into the Ganges. The plant treats less than a quarter of the current sewage output.

Most importantly, the process fails to remove pathogenic organisms that end up back in the river. Local farmers also use “treated” effluent to irrigate crop fields, contaminating nearby shallow tube wells.

According to a government audit report, GAP spent an estimated $200 million (901 crore rupees) between 1991 and 2000. For years, officials argued they had met GAP objectives despite empirical evidence that the Ganges grows ever-more polluted. “To put it simply, the plan failed,” Mishra says. “The river has never been close to healthy.”

In 1997, SMF’s proposal for construction of an algae pond system and gravity interceptor sewers was unanimously approved by the city. After the state government scuttled the plan, a subsequent lawsuit languished in the highest court for over a decade.

Until new infrastructure is built, the 40 percent of India’s population that lives in the Ganges river basin will be exposed to waterborne pathogens. Many will get sick; some will die. In-home solutions like water filters, single-dose chlorination and UV disinfection could act as temporary band-aids to purify drinking water. But the only way to curb the transmission of waterborne disease is through effective sewage treatment and access to clean drinking water, says Mishra. “We have landed on the moon and cannot do this?” he asks.

The Red-Brown Yellow River
Northwest across Asia lies another dirty “Mother River,” the Yellow River that once cradled Chinese civilization and remains the country’s spiritual home today. It snakes through 3,000 miles of mountains, plains, and farmland, past dams, factories and cities before emptying into the Bohai Sea. Some years, the mouth of the river runs dry. Though 140 million rely on it for water, certain sections run brown or red, and three-fifths of the river is too toxic for human contact. And no wonder: as of four years ago, over half of China’s 21,000 chemical plants sat on the banks of the Yellow and Yangtze rivers.

In Liangjiawan, a small, blue-collar and farming community, residents unknowingly drank untreated Yellow River water for a few years. Their water treatment plant had malfunctioned and pollutants concentrated when a new dam was built nearby. Villagers were dying of myriad cancers: pancreatic, brain, stomach, and liver. Public outcry led by Green Camel Bell, a local NGO, has sparked construction of new treatment facilities.

Across the country, three decades of double-digit economic growth have drained rivers at the same time flooding them with noxious chemicals. Unbridled rapid industrial development often has serious environmental consequences, including carcinogens in the water, said Hisashi Ogawa, the WHO’s Western Pacific regional adviser on environmental health. Despite billions of dollars spent on cleanup, lax enforcement has left 40 percent of China’s rivers undrinkable, according to a 2006 State Environmental Protection Agency (SEPA) report.

But last February, the government unveiled new data. With long-ignored agricultural chemicals factored in, water quality was twice as bad as previously reported.

Some 90 million Chinese—one in 14—must drink, bathe in, or cook with water so noxious that the World Bank warns of potential “catastrophic consequences for future generations.” Hundreds of so-called “cancer villages” cluster on polluted shorelines. Some communities suffer staggering rates of spontaneous abortion, birth defects, diminished IQs, and other maladies, says Elizabeth Economy, director of Asia Studies at the U.S. Council on Foreign Relations.

The statistics make grim reading. The WHO estimates that 22 percent of deaths in China stem from environmental causes. A 2007 government report blamed alarming jumps in cancer incidence on air and water pollution: 19 percent in cities and 23 percent in the industrialized countryside. Last year, a Fudan University study noted a serious public health risk from lead, mercury, chromium, cadmium, and arsenic. However, there is little hard data on health impacts. “No systematic epidemiological studies have been conducted proving links between industrial pollution and disease,” says Yok-shiu Lee, a University of Hong Kong urban planning professor.

Fighting back
With high medical costs and few practitioners in rural areas, many patients don’t get care or are buried in debt. The government is currently in the midst of health reform.

Citizens are becoming acutely aware of the growing health crisis. Headlines chronicle frequent industrial accidents, new cancer villages, hundreds of lead poisoning cases, and more. Beginning in 1997 the State Council pushed the mostly-state-owned media to report on environmental issues. But information-gathering is often hampered by local officials with entrenched economic interests, and there is very little oversight and massive corruption, says a health researcher who requested anonymity.

Information now spreads over the Internet, on blogs and in chat rooms, though many people are still hesitant to speak openly. In 2006, former journalist Ma Jun built an online water pollution map now consisting of 58,000 records on more than 30,000 domestic and foreign companies. His Bejing-based Institute of Public and Environmental Affairs compiles official statistics and grassroots monitoring into a searchable database. This data has shamed a few multinationals into leaning on their polluting Chinese suppliers.

About 3,000 registered environmental organizations have sprung up since the first was formed over a decade ago. Today, NGOs are activist groups that bring government and public attention to environmental issues, though they still must operate carefully within political constraints. Some educate the public about their rights. Some press for government action. Others file lawsuits against polluting industries. Without media attention or support, most pollution victims, many of whom are poor and uneducated, have little recourse.

Green Anhui is one of these activist groups. They fight for the Huai River Basin, which ranks with the Yellow, Ao, and the Yangtze as among China’s most polluted. The “ugly river” and its tributaries are riddled with factories—and health problems. Over two and a half years, 53 people from Quigang—a village of 2,000 people—died of cancer, including a toddler. Children who attended a riverside school were vomiting and suffered from nosebleeds, dizziness and diarrhea. Water quality tests were sabotaged and villagers who spoke out were beaten, according to a Woodrow Wilson Center China Environment Forum (CEF) report.

Green Anhui stepped in, focusing press and government attention on three chemical plants in nearby Bengbu. The plants were dumping benzene and other toxics into the Huai’s Baojiagou tributary in alarming quantities. It took two years to shut them down. This model is now being used in other locations, says Xiu Min Li, co-director of Pacific Environment’s China Program, Green Anhui’s California-based partner.

Even skin contact with benzene can trigger anemia, nervous system or reproductive damage, leukemia and other ills. Over a hundred tons of benzene, aniline and nitrobenzene spilled into the Songhua River when a petrochemical plant exploded in Jilin Province in November 2005. Since the river straddles the Russian border, the ensuing government cover-up caused international embarrassment and internal scandal. Xie Zhenhua, then-head of China’s environmental protection agency stepped down and a vice-mayor, Wang Wei, committed suicide.

The disaster focused public attention on the magnitude of the nation’s water pollution crisis. “The Chinese government now sees water as their most important environmental issue,” says CEF director Jennifer Turner. Laws have become more progressive, she says. She ticks off a list of gains: stronger environmental impact assessment laws, mandatory reporting of industrial pollution levels, greater public access to environmental information, and growing citizen protests. China Daily reported that roughly 50,000 environmental protests broke out in 2005; uprisings have continued.

Companies and government officials can now be brought up on criminal charges for water pollution violations. Fines and penalties are higher. “People are being told they have the right to complain, to take cases to court, and the laws are making it easier to do so,” says Turner.

Although more cases are being tried, there are few victories for pollution victims. But last year, in a landmark ruling, the head of Biaoxin Chemical Co. Ltd. was sentenced to 11 years in prison for “spreading poison.”

Implementation remains scarce. A Greenpeace China report found that few large companies were disclosing pollution data and government agencies fail to enforce the disclosure requirement.

Great distance remains between the laws on the books and enforcement on the ground, says Vermont Law School professor Jingjing Liu. Turner agrees, but she’s optimistic. She believes that the health impacts from deadly pollutants, water scarcity and growing public pressure will catalyze stronger environmental governance.

With rising populations in China, India, and the developing world, the old adage that “the solution to pollution is dilution” no longer holds true. “When you combine multi-point pollution, chemical industrial runoff, lack of infrastructure to clean the water at all, and poverty, you have a recipe for a health crisis as great as any pandemic in our history,” says Maude Barlow, U.N. senior adviser on water.

Mishra couches it differently. “The Mother is sick and needs our help,” he says.

Photo: Banks of the holy Ganges river in Varanasi / © Sharon Guynup


Water for growth and development in the Ganges, Brahmaputra, and Meghna basins: an economic perspective

Intl J River Basin Management 2015; Volume 13Issue 3,  387-400

Golam Rasula*

The Ganges, Brahmaputra, and Meghna (GBM) river system flows through five countries – Bangladesh, Bhutan, China, India, and Nepal – characterized by large population, limited land resources, and frequent floods and natural hazards. Although the GBM region is well endowed with water sources, this is one of the poorest regions in the world. Its economy and human and environmental health depend on water, and water is thus at the heart of sustainable development, economic growth, and poverty reduction. This paper examines the opportunities for, and potential socio-economic benefits of, water resource management in the GBM region in the face of changing climate. It argues that water can be an entry point for addressing challenges common to the region, particularly through multi-purpose river projects that store monsoon water, mitigate the effects of floods and droughts, augment dry season river flows, expand irrigation and navigation facilities, generate hydropower, and enhance energy and environmental security. The paper emphasizes the importance of effective regional cooperation in water management to achieve these benefits. Upstream–downstream interdependencies necessitate development of a shared river system in an integrated and collaborative manner.

Transthyretin and Lean Body Mass in Stable and Stressed State

Curator: Larry H Bernstein, MD, FCAP

A Second Look at the Transthyretin Nutrition Inflammatory Conundrum

Voluntary and Involuntary S- Insufficiency

Writer and Curator: Larry H Bernstein, MD, FCAP

Malnutrition in India, high newborn death rate and stunting of children age under five years

Larry H Bernstein, MD, FCAP, Reviewer and Curator

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Voluntary and Involuntary S- Insufficiency

Writer and Curator: Larry H Bernstein, MD, FCAP 

Transthyretin and the Stressful Condition


This article is written among a series of articles concerned with stress, obesity, diet and exercise, as well as altitude and deep water diving for extended periods, and their effects.  There is a reason that I focus on transthyretin (TTR), although much can be said about micronutients and vitamins, and fat soluble vitamins in particular, and iron intake during pregnancy.    While the importance of vitamins and iron are well accepted, the metabolic basis for their activities is not fully understood.  In the case of a single amino acid, methionine, it is hugely important because of the role it plays in sulfur metabolism, the sulfhydryl group being essential for coenzyme A, cytochrome c, and for disulfide bonds.  The distribution of sulfur, like the distribution of iodine, is not uniform across geographic regions.  In addition, the content of sulfur found in plant sources is not comparable to that in animal protein.  There have been previous articles at this site on TTR, amyloid and sepsis.

Transthyretin and Lean Body Mass in Stable and Stressed State

A Second Look at the Transthyretin Nutrition Inflammatory Conundrum

Stabilizers that prevent transthyretin-mediated cardiomyocyte amyloidotic toxicity

Thyroid Function and Disorders

Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation: a Compilation of Articles in the Journal

Malnutrition in India, high newborn death rate and stunting of children age under five years

Vegan Diet is Sulfur Deficient and Heart Unhealthy

How Methionine Imbalance with Sulfur-Insufficiency Leads to Hyperhomocysteinemia

Amyloidosis with Cardiomyopathy

Advances in Separations Technology for the “OMICs” and Clarification of Therapeutic Targets

Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control

Automated Inferential Diagnosis of SIRS, sepsis, septic shock

Transthyretin and the Systemic Inflammatory Response 

Transthyretin has been widely used as a biomarker for identifying protein-energy malnutrition (PEM) and for monitoring the improvement of nutritional status after implementing a nutritional intervention by enteral feeding or by parenteral infusion. This has occurred because transthyretin (TTR) has a rapid removal from the circulation in 48 hours and it is readily measured by immunometric assay. Nevertheless, concerns have been raised about the use of TTR in the ICU setting, which prompts a review of the actual benefit of using this test in a number of settings. TTR is easily followed in the underweight and the high risk populations in an ambulatory setting, which has a significant background risk of chronic diseases.  It is sensitive to the systemic inflammatory response syndrom (SIRS), and needs to be understood in the context of acute illness to be used effectively. There are a number of physiologic changes associated with SIRS and the injury/repair process that will affect TTR and will be put in context in this review. The most important point is that in the context of an ICU setting, the contribution of TTR is significant in a complex milieu.  copyright @ Bentham Publishers Ltd. 2009.

Transthyretin as a marker to predict outcome in critically ill patients.
Arun Devakonda, Liziamma George, Suhail Raoof, Adebayo Esan, Anthony Saleh, Larry H. Bernstein.
Clin Biochem Oct 2008; 41(14-15): 1126-1130

A determination of TTR level is an objective method od measuring protein catabolic loss of severly ill patients and numerous studies show that TTR levels correlate with patient outcomes of non-critically ill patients. We evaluated whether TTR level correlates with the prevalence of PEM in the ICUand evaluated serum TTR level as an indicator of the effectiveness of nutrition support and the prognosis in critically ill patients.

TTR showed excellent concordance with patients classified with PEM or at high malnutrition risk, and followed for 7 days, it is a measure of the metabolic burden. TTR levels did not respond early to nutrition support because of the delayed return to anabolic status. It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition.

 The Stressful Condition as a Nutritionally Dependent Adaptive Dichotomy

Yves Ingenbleek and Larry Bernstein
Nutrition 1999;15(4):305-320 PII S0899-9007(99)00009-X

The injured body manifests a cascade of cytokine-induced metabolic events aimed at developing defense mechanisms and tissue repair. Rising concentrations of counterregulatory hormones work in concert with cytokines to generate overall insulin and insulin-like growth factor 1 (IGF-1), postreceptor resistance and energy requirements grounded on lipid dependency. Dalient features are self-sustained hypercortisolemia persisting as long as cytokines are oversecreted and down-regulation of the hypothalamo-pituitary-thyroid axis stabilized at low basal levels. Inhibition of thyroxine 5’deiodinating activity (5’DA) accounts for the depressed T3 values associated with the sparing of both N and energy-consuming processes. Both the liver and damaged territories adapt to stressful signals along up-regulated pathways disconnected from the central and peripheral control systems. Cytokines stimulate 5’DA and suppress the synthesis of TTR, causing the drop of retinol-binding protein (RBP) and the leakage of increased amounts of T4 and retinol in free form. TTR and RBP thus work as prohormonal reservoirs of precursor molecules which need to be converted into bioactive derivatives (T3 and retinoic acids) to reach transcriptional efficiency. The converting steps (5’DA and cellular retinol-binding protein-1) are activated to T4 and retinol, themselves operating as limiting factors to positive feedback loops. …The suicidal behavior of TBG, CBG, and IGFBP-3 allows the occurrence of peak endocrine and mitogenic influences at the site of inflammation. The production rate of TTR by the liver is the main determinant of both the hepatic release and blood transport of holoRBP, which explains why poor nutritional status concomitantly impairs thyroid- and retinoid-dependent acute phase responses, hindering the stressed body to appropriately face the survival crisis.  …
abbreviations: TBG, thyroxine-binding globulain; CBG, cortisol-binding globulin; IGFBP-3, insulin growth factor binding protein-3; TTR, transthyretin; RBP, retionol-binding protein.

Why Should Plasma Transthyretin Become a Routine Screening Tool in Elderly Persons? 

Yves Ingenbleek.
J Nutrition, Health & Aging 2009.

The homotetrameric TTR molecule (55 kDa as MM) was first identified in cerebrospinal fluid (CSF).  The initial name of prealbumin (PA)  was assigned based on the electrophoretic migration anodal to albumin. PA was soon recognized as a specific binding protein for thyroid hormone. and also of plasma retinol through the mediation of the small retinol-binding protein (RBP, 21 kDa as MM), which has a circulating half-life half that of TTR (24 h vs 48 h).

There exist at least 3 goos reasons why TTR should become a routine medical screening test in elderly persons.  The first id grounded on the assessment of protein nutritional status that is frequently compromized and may become a life threatening condition.  TTR was proposed as a marker of protein-energy malnutrition (PEM) in 1972. As a result of protein and energy deprivation, TTR hepatic synthesis is suppressed whereas all plasma indispensable amino acids (IAAs) manifest declining trends with the sole exception of methionine (Met) whose concentration usually remains unmodified. By comparison with ALB and transferrin (TF) plasma values, TTR did reveal a much higher degree of reactivity to changes in protein status that has been attributed to its shorter biological half-life and to its unusual tryptophan richness. The predictive ability of outcome offered by TTR is independent of that provided by ALB and TF. Uncomplicated PEM primarily affects the size of body nitrogen (N) pools, allowing reduced protein syntheses to levels compatible with survival.  These adaptiver changes are faithfully identified by the serial measurement of TTR whose reliability has never been disputed in protein-depleted states. On the contrary, the nutritional relevance of TTR has been controverted in acute and chronic inflammatory conditions due to the cytokine-induced transcriptional blockade of liver synthesis which is an obligatory step occurring independently from the prevailing nutritional status. Although PEM and stress ful disorders refer to distinct pathogenic mechanisms, their combined inhibitory effects on TTR liber production fueled a long-lasting strife regarding a poor specificity.  Recent body compositional studies have contributed to disentagling these intermingled morbidities, showing that evolutionary patterns displayed by plasma TTR are closely correlated with the fluctuations of lean body mass (LBM).

The second reason follows from advances describing the unexpected relationship established between TTR and homocysteine (Hcy), a S-containing AA not found in customary diets but resulting from the endogenous transmethylation of dietary methionine.  Hcy may be recycled to Met along a remethylation pathway (RM) or irreversibly degraded throughout the transsulfuration (TS) cascade to relase sulfaturia as end-product. Hcy is thus situated at the crossrad of RM and TS pathways which are in equilibrium keeping plasma Met values unaltered.  Three dietary water soluble B viatamins are implicated in the regulation of the Hcy-Met cycle. Folates (vit B9) are the most powerful agent, working as a supplier of the methyl group required for the RM process whereas cobalamines (vit B12) and pyridoxine (vit B6) operate as cofactors of Met-synthase and cystathionine-β-synthase.  Met synthase promotes the RM pathway whereas the rate-limiting CβS governs the TS degradative cascade. Dietary deficiency in any of the 3 vitamins may upregulate Hcy plasma values, an acquied biochemiucal anomaly increasingly encountered in aged populations.

The third reason refers to recent and fascinating data recorded in neurobiology and emphasizing the specific properties of TTR in the prevention of brain deterioration. TTR participates directly in the maintenance of memory and normal cognitive processes during the aging process by acting on the retinoid signaling pathway.  Moreover, TTR may bind amyloid β peptide in vitro, preventing its transformation into toxic amyloid fibrils and amyloid plaques.  TTR works as a limiting factor for the plasma transport of retinoid, which in turn operates as a limiting determinant of both physiologically active retinoic acid (RA) derivatives, implying that any fluctuation in protein status might well entail corresponding  alterations in cellular bioavailability of retinoid compounds.  Under normal aging circumstances, the concentration of retinoid compounds declines in cerebral tissues together with the downregulation of RA receptor expression. In animal models, depletion of RAs causes the deposition of amyloid-β peptides, favoring the formation of amyloid plaques.

Prealbumin and Nutritional Evaluation

Larry Bernstein, Walter Pleban
Nutrition Apr 1996; 12(4):255-259.

We compressed 16-test-pattern classes of albumin (ALB), cholesterol (CHOL), and total protein (TPR) in 545 chemistry profiles to 4 classes by conveerting decision values to a number code to separate malnourished (1 or 2) from nonmalnourished (NM)(0) patients using as cutoff values for NM (0), mild (1), and moderate (2): ALB 35, 27 g/L; TPR 63, 53 g/L; CHOL 3.9, 2.8 mmol/L; and BUN 9.3, 3.6 mmol/L. The BUN was found to have  to have too low an S-value to make a contribution to the compressed classification. The cutoff values for classifying the data were assigned prior to statistical analysis, after examining information in the structured data. The data was obtained by a natural experiment in which the test profiles routinely done by the laboratory were randomly extracted. The analysis identifies the values used that best classify the data and are not dependent on distributional assumptions. The data were converted to 0, 1, or 2 as outcomes, to create a ternary truth table (eaxch row in nnn, the n value is 0 to 2). This allows for 3(81) possible patterns, without the inclusion of prealbumin (TTR). The emerging system has much fewer patterns in the information-rich truth table formed (a purposeful, far from random event). We added TTR, coded, and examined the data from 129 patients. The classes are a compressed truth table of n-coded patterns with outcomes of 0, 1, or 2 with protein-energy malnutrition (PEM) increasing from an all-0 to all-2 pattern.  Pattern class (F=154), PAB (F=35), ALB (F=56), and CHOL (F=18) were different across PEM class and predicted PEM class (R-sq. = 0.7864, F=119, p < E-5). Kruskall-Wallis analysis of class by ranks was significant for pattern class E-18), TTR (6.1E-15) ALB (E-16), CHOL (9E-10), and TPR (5E-13). The medians and standard error (SEM) for TTR, ALB, and CHOL of four TTR classes (NM, mild, mod, severe) are: TTR = 209, 8.7; 159, 9.3; 137, 10.4; 72, 11.1 mg/L. ALB – 36, 0.7; 30.5, 0.8; 25.0, 0.8; 24.5, 0.8 g/L. CHOL = 4.43, 0.17; 4.04, 0.20; 3.11, 0.21; 2.54, 0.22 mmol/L. TTR and CHOL values show the effect of nutrition support on TTR and CHOL in PEM. Moderately malnourished patients receiving nutrition support have TTR values in the normal range at 137 mg/L and at 159 mg/L when the ALB is at 25 g/L or at 30.5 g/L.

An Informational Approach to Likelihood of Malnutrition 

Larry Bernstein, Thomas Shaw-Stiffel, Lisa Zarney, Walter Pleban.
Nutrition Nov 1996;12(11):772-776.  PII: S0899-9007(96)00222-5.

Unidentified protein-energy malnutrition (PEM) is associated with comorbidities and increased hospital length of stay. We developed a model for identifying severe metabolic stress and likelihood of malnutrition using test patterns of albumin (ALB), cholesterol (CHOL), and total protein (TP) in 545 chemistry profiles…They were compressed to four pattern classes. ALB (F=170), CHOL (F = 21), and TP (F = 5.6) predicted PEM class (R-SQ = 0.806, F= 214; p < E^-6), but pattern class was the best predictor (R-SQ = 0.900, F= 1200, p< E^-10). Ktuskal-Wallis analysis of class by ranks was significant for pattern class (E^18), ALB (E^-18), CHOL (E^-14), TP (@E^-16). The means and SEM for tests in the three PEM classes (mild, mod, severe) were; ALB – 35.7, 0.8; 30.9, 0.5; 24.2, 0.5 g/L. CHOL – 3.93, 0.26; 3.98, 0.16; 3.03, 0.18 µmol/L, and TP – 68.8, 1.7; 60.0, 1.0; 50.6, 1.1 g/L. We classified patients at risk of malnutrition using truth table comprehension.

Downsizing of Lean Body Mass is a Key Determinant of Alzheimer’s Disease

Yves Ingenbleek, Larry Bernstein
J Alzheimer’s Dis 2015; 44: 745-754.

Lean body mass (LBM) encompasses all metabolically active organs distributed into visceral and structural tissue compartments and collecting the bulk of N and K stores of the human body. Transthyretin (TTR)  is a plasma protein mainly secreted by the liver within a trimolecular TTR-RBP-retinol complex revealing from birth to old age strikingly similar evolutionary patterns with LBM in health and disease. TTR is also synthesized by the choroid plexus along distinct regulatory pathways. Chronic dietary methionine (Met) deprivation or cytokine-induced inflammatory disorders generates LBM downsizing following differentiated physiopathological processes. Met-restricted regimens downregulate the transsulfuration cascade causing upstream elevation of homocysteine (Hcy) safeguarding Met homeostasis and downstream drop of hydrogen sulfide (H2S) impairing anti-oxidative capacities. Elderly persons constitute a vulnerable population group exposed to increasing Hcy burden and declining H2S protection, notably in plant-eating communities or in the course of inflammatory illnesses. Appropriate correction of defective protein status and eradication of inflammatory processes may restore an appropriate LBM size allowing the hepatic production of the retinol circulating complex to resume, in contrast with the refractory choroidal TTR secretory process. As a result of improved health status, augmented concentrations of plasma-derived TTR and retinol may reach the cerebrospinal fluid and dismantle senile amyloid plaques, contributing to the prevention or the delay of the onset of neurodegenerative events in elderly subjects at risk of Alzheimer’s disease.

Amyloidogenic and non-amyloidogenic transthyretin variants interact differently with human cardiomyocytes: insights into early events of non-fibrillar tissue damage

Pallavi Manral and Natalia Reixach

TTR (transthyretin) amyloidosis are diseases characterized by the aggregation and extracellular deposition of the normally soluble plasma protein TTR. Ex vivo and tissue culture studies suggest that tissue damage precedes TTR fibril deposition, indicating that early events in the amyloidogenic cascade have an impact on disease development. We used a human cardiomyocyte tissue culture model system to define these events. We previously described that the amyloidogenic V122I TTR variant is cytotoxic to human cardiac cells, whereas the naturally occurring, stable and non-amyloidogenic T119M TTR variant is not. We show that most of the V122I TTR interacting with the cells is extracellular and this interaction is mediated by a membraneprotein(s). In contrast, most of the non-amyloidogenic T119M TTR associated with the cells is intracellular where it undergoes lysosomal degradation. The TTR internalization process is highly dependent on membrane cholesterol content. Using a fluorescent labelled V122I TTR variant that has the same aggregation and cytotoxic potential as the native V122I TTR, we determined that its association with human cardiomyocytes is saturable with a KD near 650nM. Only amyloidogenic V122I TTR compete with fluorescent V122I force ll-binding sites. Finally, incubation of the human cardiomyocytes with V122I TTR but not with T119M TTR, generates superoxide species and activates caspase3/7. In summary, our results show that the interaction of the amyloidogenic V122I TTR is distinct from that of a non-amyloidogenic TTR variant and is characterized by its retention at the cell membrane, where it initiates the cytotoxic cascade.

Emerging roles for retinoids in regeneration and differentiation in normal and disease states

Lorraine J. Gudas
Biochimica et Biophysica Acta 1821 (2012) 213–221

The vitamin (retinol) metabolite, all-transretinoic acid (RA), is a signaling molecule that plays key roles in the development of the body plan and induces the differentiation of many types of cells. In this review the physiological and pathophysiological roles of retinoids (retinol and related metabolites) in mature animals are discussed. Both in the developing embryo and in the adult, RA signaling via combinatorial Hoxgene expression is important for cell positional memory. The genes that require RA for the maturation/differentiation of T cells are only beginning to be cataloged, but it is clear that retinoids play a major role in expression of key genes in the immune system. An exciting, recent publication in regeneration research shows that ALDH1a2(RALDH2), which is the rate-limiting enzyme in the production of RA from retinaldehyde, is highly induced shortly after amputation in the regenerating heart, adult fin, and larval fin in zebrafish. Thus, local generation of RA presumably plays a key role in fin formation during both embryogenesis and in fin regeneration. HIV transgenic mice and human patients with HIV-associated kidney disease exhibit a profound reduction in the level of RARβ protein in the glomeruli, and HIV transgenic mice show reduced retinol dehydrogenase levels, concomitant with a greater than 3-fold reduction in endogenous RA levels in the glomeruli. Levels of endogenous retinoids (those synthesized from retinol within cells) are altered in many different diseases in the lung, kidney, and central nervous system, contributing to pathophysiology.

The Membrane Receptor for Plasma Retinol-Binding Protein, A New Type of Cell-Surface Receptor

Hui Sun and Riki Kawaguchi
Intl Review Cell and Molec Biol, 2011; 288:Chap 1. Pp 1:34

Vitamin A is essential for diverse aspects of life ranging from embryogenesis to the proper functioning of most adul torgans. Its derivatives (retinoids) have potent biological activities such as regulating cell growth and differentiation. Plasma retinol-binding protein (RBP) is the specific vitamin A carrier protein in the blood that binds to vitamin A with high affinity and delivers it to target organs. A large amount of evidence has accumulated over the past decades supporting the existence of a cell-surface receptor for RBP that mediates cellular vitamin A uptake. Using an unbiased strategy, this specific cell-surface RBP receptor has been identified as STRA6, a multi-transmembrane domain protein with previously unknown function. STRA6 is not homologous to any protein of known function and represents a new type of cell-surface receptor. Consistent with the diverse functions of vitamin A, STRA6 is widely expressed in embryonic development and in adult organ systems. Mutations in human STRA6 are associated with severe pathological phenotypes in many organs
such as the eye, brain, heart, and lung. STRA6 binds to RBP with high affinity and mediates vitamin A uptake into cells. This review summarizes the history of the RBP receptor research, its expression in the context of known functions of vitamin A in distinct human organs, structure/function analysis of this new type of membrane receptor, pertinent questions regarding its very existence, and its potential implication in treating human diseases.

Choroid plexus dysfunction impairs beta-amyloid clearance in a triple transgenic mouse model of Alzheimer’s disease

Ibrahim González-Marrero, Lydia Giménez-Llort, Conrad E. Johanson, et al.
Front Cell Neurosc  Feb2015; 9(17): 1-10

Compromised secretory function of choroid plexus (CP) and defective cerebrospinal fluid (CSF) production, along with accumulation of beta-amyloid (Aβ) peptides at the blood-CSF barrier (BCSFB), contribute to complications of Alzheimer’s disease (AD). The AD triple transgenic mouse model (3xTg-AD) at 16 month-old mimics critical hallmarks of the human disease: β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) with a temporal-and regional-specific profile. Currently, little is known about transport and metabolic responses by CP to the disrupted homeostasis of CNS Aβ in AD. This study analyzed the effects of highly-expressed AD-linked human transgenes (APP, PS1 and tau) on lateral ventricle CP function. Confocal imaging and immunohistochemistry revealed an increase only of Aβ42 isoform in epithelial cytosol and in stroma surrounding choroidal capillaries; this buildup may reflect insufficient clearance transport from CSF to blood. Still, there was increased expression, presumably compensatory, of the choroidal Aβ transporters: the low density lipoprotein receptor-related protein1 (LRP1) and the receptor for advanced glycation end product (RAGE). A thickening of the epithelial basal membrane and greater collagen-IV deposition occurred around capillaries in CP, probably curtailing solute exchanges. Moreover, there was attenuated expression of epithelial aquaporin-1 and transthyretin(TTR) protein compared to Non-Tg mice. Collectively these findings indicate CP dysfunction hypothetically linked to increasing Aβ burden resulting in less efficient ion transport, concurrently with reduced production of CSF (less sink action on brain Aβ) and diminished secretion of TTR (less neuroprotection against cortical Aβ toxicity). The putative effects of a disabled CP-CSF system on CNS functions are discussed in the context of AD.

Endoplasmic reticulum: The unfolded protein response is tangled In neurodegeneration

Jeroen J.M. Hoozemans, Wiep Scheper
Intl J Biochem & Cell Biology 44 (2012) 1295–1298

Organelle facts•The ER is involved in the folding and maturation ofmembrane-bound and secreted proteins.•The ER exerts protein quality control to ensure correct folding and to detect and remove misfolded proteins.•Disturbance of ER homeostasis leads to protein misfolding and induces the UPR.•Activation of the UPR is aimed to restore proteostasis via an intricate transcriptional and (post)translational signaling network.•In neurodegenerative diseases classified as tauopathies the activation of the UPR coincides with the pathogenic accumulation of the microtubule associated protein tau.•The involvement of the UPR in tauopathies makes it a potential therapeutic target.

The endoplasmic reticulum (ER) is involved in the folding and maturation of membrane-bound and secreted proteins. Disturbed homeostasis in the ER can lead to accumulation of misfolded proteins, which trigger a stress response called the unfolded protein response (UPR). In neurodegenerative diseases that are classified as tauopathies, activation of the UPR coincides with the pathogenic accumulation of the microtubule associated protein tau. Several lines of evidence indicate that UPR activation contributes to increased levels of phosphorylated tau, a prerequisite for the formation of tau aggregates. Increased understanding of the crosstalk between signaling pathways involved in protein quality control in the ERand tau phosphorylation will support the development of new therapeutic targets that promote neuronal survival.

Chemical and/or biological therapeutic strategies to ameliorate protein misfolding diseases

Derrick Sek Tong Ong and Jeffery W Kelly
Current Opin Cell Biol 2011; 23:231–238

Inheriting a mutant misfolding-prone protein that cannot be efficiently folded in a given cell type(s) results in a spectrum of human loss-of-function misfolding diseases. The inability of the biological protein maturation pathways to adapt to a specific misfolding-prone protein also contributes to pathology. Chemical and biological therapeutic strategies are presented that restore protein homeostasis, or proteostasis, either by enhancing the biological capacity of the proteostasis network or through small molecule stabilization of a specific misfolding-prone protein. Herein, we review the recent literature on therapeutic strategies to ameliorate protein misfolding diseases that function through either of these mechanisms, or a combination thereof, and provide our perspective on the promise of alleviating protein misfolding diseases by taking advantage of proteostasis adaptation.

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