6. Collinge J, Sidle KCL, Meads J, Ironside J, Hill AF. Molecular analysis of prionstrain variation and the aetiology of ‘new variant’ CJD. Nature 1996;383:685

7. Brown P, Preece MA, Will RG. “Friendly fire” in medicine: hormones, ho-mografts, and Creutzfeldt–Jakob disease. Lancet 1992;340:24

8. Brown P. Donor pool size and the risk of blood-borne Creutzfeldt–Jakob disease.Transfusion 1998;38:312

9. Young K, Piccardo P, Dlouhy S, et al. In: Harris DA, ed.Prions: molecular andcellular biology. Wymondham: Horizon Scientific Press, 1999:139

10. Lehmann S, Harris DA. Mutant and infectious prion proteins display commonbiochemical properties in cultured cells. J Biol Chem 1996;271:1633

11. Chiesa R, Piccardo P, Ghetti B, Harris DA. Neurological illness in transgenicmice expressing a prion protein with an insertional mutation. Neuron 1998;21:1339

12. Alper T, Cramp WA, Haig DA, Clarke MC. Does the agent of scrapie replicatewithout nucleic acid? Nature 1967;214:764

13. Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science1982;216:136

14. Prusiner SB, Groth DF, Bolton DC, Kent SB, Hood LE. Purification and struc-tural properties of a major scrapie prion protein. Cell 1984;38:127

15. Griffith JS. Self-replication and scrapie. Nature 1967;215:104316. Oesch B, Westaway D, Walchli M, et al. A cellular gene encodes scrapie PrP

27-30 protein. Cell 1985;40:735

17. Pauly PC, Harris DA. Copper stimulates endocytosis of the prion protein. J BiolChem 1998;273:33107

18. Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95:1336319. Pan K-M, Baldwin M, Nguyen J, et al. Conversion of a-helices into b-sheets

features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA1993;90:10962

20. Donne DG, Viles JH, Groth D, et al. Structure of the recombinant full-lengthhamster prion protein PrP(29-231): the N terminus is highly flexible. Proc NatlAcad Sci USA 1997;94:13452

21. Riek R, Hornemann S, Wider G, et al. NMR structure of the mouse prion proteindomain PrP(121-231). Nature 1996;382:180

22. Bueler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie.Cell 1993;73:1339

23. Prusiner SB, Scott M, Foster D, et al. Transgenetic studies implicate interactionsbetween homologous PrP isoforms in scrapie prion replication. Cell 1990;63:673

24. Kocisko DA, Come JH, Priola SA, et al. Cell-free formation of protease-resistantprion protein. Nature 1994;370:471

25. Kaneko K, et al. A synthetic peptide initiates Gerstmann–Stra¨ussler–Scheinker(GSS) disease in transgenic mice. J Mol Biol 2000;295:997

26. Welch WJ, Gambetti P. Chaperoning brain diseases. Nature 1998;392:2327. Wickner RB, Edskes HK, Maddelein ML, Taylor KL, Moriyama H. Prions of

yeast and fungi. Proteins as genetic material. J Biol Chem 1999;274:555

Malnutrition: Causes, Consequences, andSolutions

Sarath Gopalan, MDFrom the Pushpawati Singhania Research Institute, New Delhi, India

INTRODUCTION

As we enter the 21st century and the new millennium, malnutri-tion, acting either directly or indirectly, remains the single mostimportant factor impairing health and productivity of large humanpopulations. The ongoing demographic and developmental transi-tion has brought about a steady change in the profile of malnutri-tion, especially in the latter half of the previous century. This hasbeen particularly noticeable in the developing countries.1 Untilapproximately 50 y ago, malnutrition was largely considered to bethe problem of the poor. Famines, due to acute shortage of food,periodically devastated vast populations in Asia and Africa. Florid,classic nutritional deficiency diseases such as kwashiorkor, kera-tomalacia, pellagra, beriberi, and goitre took a heavy toll. Thanksto the timely advent of the “green revolution,” gloomy Malthusianprophecies of near extinction of populations from famine werebelied. Florid nutritional-deficiency diseases were largely broughtunder control. However, considerable undernutrition reflected in“mild” and “moderate” malnutrition, stunting in children, andanemias in pregnancy associated with low–birth-weight deliveriesare still widely prevalent in many parts of the Third World. Thus,nearly half of children younger than 5 y in South Asia are presentlystunted and nearly one-third of infants born are of low birth weight(,2.5 kg).2

Although undernutrition continues to be a problem of the poor,especially among children and women of developing countries,there has been disturbing evidence of escalation of the incidence of

nutrition-related chronic diseases such as obesity, coronary heartdisease, and diabetes mellitus among adults of the relatively af-fluent sections of the developed and developing countries. As aresult, developing countries in particular face the double burden ofundernutrition among poor women and children at one end of thesocioeconomic spectrum and of malnutrition among the relativelyaffluent adults of the middle class at the other end.3

There is growing evidence that populations of the Third World,emerging from poverty into affluence with consequent changes indiets and lifestyles, may be more vulnerable and prone to suchchronic degenerative diseases. Indian immigrants to the UnitedKingdom, for instance, have been found to suffer more fromcoronary heart disease and diabetes than either natives of theUnited Kingdom or their own national counterparts belonging totheir erstwhile socioeconomic class in India.4

The fascinating work of Barker et al.5 suggests that the mani-festations of malnutrition at the two ends of the socioeconomicspectrum may indeed be causally and metabolically related. Theirobservations indicate that intrauterine growth retardation could so“program” the fetal tissues as to render them more vulnerable tonutrition-related disorders such as syndrome X and chronic degen-erative diseases in later adult life. In short, according to theirfar-reaching hypothesis, nutrition-related chronic diseases of adult-hood could be the “late” effects of early fetal undernutrition. Thoseborn in poverty with intrauterine growth retardation and attainingaffluence in later adult life may be special victims!

CAUSES OF MALNUTRITION

Undernutrition, widely prevalent, especially in developing coun-tries, is part of the so-called poverty syndrome, which has themutually synergistic attributes of low family income, large familysize, poor education, poor environment and housing, poor access to

Correspondence to: Sarath Gopalan, MD, Consultant in Paediatric Gastro-enterology and Clinical Nutrition, Pushpawati Singhania Research Insti-tute, Honorary Director CRNSS, Nutrition Foundation of India Building,C-13 Qutab Institutional Area, New Delhi 110016, India. E-mail:nfi@ren02.nic.in or crnss@hotmail.com

556 Gopalan Nutrition Volume 16, Numbers 7/8, 2000

health care, and inadequate access to food. Actually one-third ofhouseholds in some developing countries today are caught in thispoverty trap. The two main factors that could account for inade-quate access to foods by poor households are 1) inadequate avail-ability of food at the overall nutritional levels and 2) inequitabledistribution of food available within the country, with poor house-holds being the main sufferers. It is now clear that it is not the lackof overall availability of food at the national level but ratherpoverty at the level of individual households that is the majorfactor underlying undernutrition. We are witness to the cruelparadox of impressive buffer stocks of food grains at the nationallevels, on the one hand, and several pockets of poverty andundernutrition within the countries, on the other.

A close correlation between the level of female literacy in acountry, on the one hand, and child mortality rate and nutritionalstatus of children, on the other, has been observed (Table I). Thelevel of female education is apparently a major determinant ofhealth and nutritional status. Apparently, even in families with lowincome, educated mothers prove more resourceful in managingmeager resources in a manner that will ensure maximal possiblebenefit with respect to health and nutrition status of their families.Poor education and ignorance are also reflected in an inequitableintrafamilial distribution of food, with young children and womenbeing the worst sufferers. The diets of young children between 6mo and 2 y of age inpoor households are particularly inadequatewith respect to both quantity and quality. Even a small part of thediet available within the family could help correct a good part ofthese deficiencies.

It is ignorance rather than lack of adequate food within thefamily that is often responsible for lack of proper nutritional careamong pregnant women. The need for ensuring adequacy of foodespecially during pregnancy is hardly appreciated; as a result, inpoor households, diets of women during pregnancy are even worsethan during their non-pregnant state.

Environmental sanitation, poor housing conditions, and lack ofproper personal hygiene often aggravated by scarcity of waterfavor the development of acute gastrointestinal infections, espe-cially in children. Diarrheas and respiratory diseases account forconsiderable morbidity and contribute to the aggravation of un-dernutrition. The mutual deleterious synergistic interaction be-tween undernutrition and infection is now widely appreciated.Lack of adequate access to prompt treatment also helps to prolong

the duration of illnesses, with consequent worsening of nutritionstatus. The prevalence of widespread stunting in children youngerthan 5 y is attributable to the confluence of these synergistic factorsof the poverty syndrome.

MALNUTRITION IN AFFLUENT ADULTS

The disturbing escalation of the incidence of nutrition-relatedchronic degenerative diseases of adults, namely, obesity, coronaryheart disease, and diabetes, is in a sense the price of “develop-ment.” It is also true that as part of “development” life expectancyhas steadily risen in several developing countries; and, as a result,many more children are now attaining adulthood. This may beexpected to contribute to some extent to the observed increase inthe incidence of chronic degenerative diseases. However, the factthat there has been an increase in age-specific mortality andmorbidity due to chronic degenerative diseases will show thatincreased life expectancy is not the total explanation. Developmentbrings in its train changes in dietary habits and lifestyles. There areimportant dietary changes that take place in the population as theymove up in the socioeconomic scale6:

1. Substitution of millet (so-called coarse grains) by the moreprestigious cereals wheat and rice, with increasing prefer-ence for the highly polished varieties of the latter. Thissubstitution is usually accompanied by reduction in overallcereal intake (although cereal intake by European andNorth-American standards continues to be relatively high).These changes could result in a significant decrease in theoverall fiber content of the diet. Fiber content of polishedrice is just 2.4 g/100 g and that of refined wheat is 3.0 g/100g versus a fiber content of 20.4 g%, 18.6 g%, and 14.2 g%in bajra (Pennisetum typhoideum), ragi (Eleusime cora-cana), and jowar (Sorghum vulgare), respectively. Underthe circumstances, the total substitution of millet by rice orwheat could result in almost 50% reduction in fiber content.The fiber content of raw rice (brown) is 5–8 g/100 g versus2.4 g/100 g for polished rice, and the fiber content of wholemeal wheat (100%) is 9.6 g/100 g versus 3.0 g/100 g forrefined wheat.

2. Progressive increase in the intake of edible fat, with increas-ing preference for hydrogenated fat in place of vegetableoils (in the case of the middle classes) and relatively highintake of ghee (clarified butter; in the most prosperoussegments). Hydrogenated fat is a good source of trans-fattyacids, which have been proven to be deleterious.

3. Increased intake of sugar.4. Increase in overall energy intake in relation to energy ex-

penditure. The degree of vigorous physical activities char-acteristic of the lifestyles of the rural working class is hardlyto be seen among the urban middle class, whose occupationsare usually sedentary and whose daily lifestyles hardly allowmuch time for regular exercise.

Apart from these factors in the urban context, the possible rolesof stress, incidental to competitive occupations, on the one hand,and intense air pollution, contributing noxious oxidants to theenvironment, on the other, also have to be considered.

There are two questions of considerable practical importancewith respect to the escalation of the incidence of chronic degen-erative infections now being seen among the urban middle class ofdeveloping countries, especially those of South Asia:

1. Are these populations genetically more prone to degenera-tive diseases? or

2. Is this escalation a “first-generation” phenomenon to be seenlargely in those born in poverty and acquiring affluence inadult life? In short, is this phenomenon explicable on thebasis of Barker’s hypothesis?

These questions are important. If the second question is an-swered affirmately, it will be legitimate to expect that the overall

TABLE I.

CORRELATION OF FEMALE LITERACY RATE WITHMORTALITY RATE OF CHILDREN YOUNGER THAN 5 Y AND

PERCENTAGE OF LOW BIRTH WEIGHT*

CountryFemale literacy

(1995)Mortality

(1997)Low birth weight

(1997)

Philippines 94 41 9Thailand 92 38 6Vietnam 91 43 17Sri Lanka 87 19 25Singapore 86 4 7Malaysia 78 11 8Indonesia 78 68 8Myanmar 78 114 24China 73 47 9India 38 108 33Pakistan 24 136 25Bhutan 28 121 —Bangladesh 26 109 50Nepal 14 104 —

* From The State of the World’s Children.Geneva: UNICEF, 1999

Nutrition Volume 16, Numbers 7/8, 2000 557Malnutrition: Causes, Consequences, and Solutions

increase in the incidence of chronic degenerative disease in theurban affluent population in some developing countries is likely tobe a transient phenomenon incidental to developmental transition.

SOLUTIONS

Undernutrition, which is widely prevalent among poor populationsespecially in developing countries, can, in the ultimate analysis, beovercome not by narrow vertical program limited to supplemen-tation of one or more synthetic nutrients or by state welfare feedingbut by improvement of habitual diets in households. In situationsof dire poverty and consequent hunger, the immediate need is forenergy-rich foods such as cereals and millets. Most diets in verypoor households, among whom malnutrition is widespread, consistpredominantly of such cereals and millets, with very little of“protective” foods such as vegetables, fruits, pulses (legumes), andmilk. However, as pointed out above, in a considerable proportionof poor households, it should be possible to promote better intakeof vegetables and pulses even under present socioeconomic con-ditions through a program of nutrition education. The challenge isto achieve diversification and broadening of the dietary base. Thepresent intake of vegetables in poor South-Asian diets is approx-imately 50 g/d as opposed 150 g/d in Southeast-Asian countriesand at least 400 g/d in China and the United States. The vastbiodiversity prevailing in Asia favors the augmentation of theproduction and consumption of vegetables. However, a vigorous,sustained program of nutrition education is needed to bring aboutthis change.

In the wake of the green revolution, pulse production haslagged behind and pulse intake has declined. This decline needs tobe corrected because pulses ensure protein quality in predomi-nantly cereal-based diets. Milk production and intake have, how-ever, significantly increased in the past few years in India, and withimproved technology it would be possible to augment the produc-tion even more.

The solution to problems of undernutrition must, in the ultimateanalysis, be based on food. A blunderbuss polypharmacy approachof providing a cocktail of synthetic nutrients cannot be the solutionin public health because no such cocktail can be nutritionally andphysiologically a substitution for proper food. The task of address-ing current deficiencies in diets from dietary deprivation cannot beevaded through resort to such soft pharmaceutical options.

In recent years, natural foods have been shown to contain, in

addition to the conventional macro- and micronutrients, a wholerange of bioactive phytochemicals that have health-promoting anddisease-preventing properties. Some of the traditional foods invogue in India and China such as turmeric and fenugreek havebeen shown to contain valuable health-promoting chemicals. Thesolution to the problem of undernutrition in poor households indeveloping countries largely consists of identifying and promotingthe consumption of inexpensive, locally available foods within theeconomic and geographic reach of even poor families. Apart fromiron (and folate) and iodine, synthetic supplements will seldom benecessary except in special situations where specific deficiencydiseases have been found to be prevalent in some highly deprivedareas.

The prevention and control of nutrition-related chronic degen-erative diseases among the affluent will call for two major ap-proaches: 1) avoidance of dietary excesses and 2) promotion ofoptimal physical activity to ensure that energy input does notunduly exceed energy expenditure. Diets consisting primarily ofcereals and vegetables not only provide fiber but also generallyfavor low serum cholesterol and optimal blood lipid profile. Theavoidance of excessive (saturated) fats, high intake of animalproteins, and excessive intake of alcohol and the inclusion of fatswith a proper balance betweenv-6 andv-3 fatty acids (such asadvocated in the omega plan)7 will be conducive to optimalnutrition.

REFERENCES

1. Gopalan C. Nutrition and developmental transition: lessons from Asian experi-ence. NFI Bul 1999;20:4

2. Ramachandran P. Low birth weights: the Indian experience. NFI Bull 1993;14:43. Shetty P. Diet, lifestyle and chronic disease: lessons from contrasting worlds. In:

Diet, nutrition and chronic disease: lessons from contrasting worlds. Chichester:Wiley, 1997:269

4. McKeigue PM. Cardiovascular disease and diabetes in migrants: interaction be-tween nutritional changes and genetic background. In:Diet, nutrition and chronicdisease: lessons from contrasting worlds. Chichester: Wiley, 1997:59

5. Barker DJP. Prenatal influences on disease in later life. In:Diet, nutrition andchronic disease: lessons from contrasting worlds. Chichester: Wiley, 1997:41

6. Gopalan C. Dietary guidelines from the perspective of developing countries.Presented at the International Conference on Dietary Guidelines, June 1988,Reyson Polytechnical Institute;Toronto, Canada

7. Simopoulos AP, Robinson J.The omega plan. New York: Harper Collins Pub-lishers, 1998

Is Fiber Protective Against Colon Cancer?Where the Research Is Leading Us

Joanne R. Lupton, PhDFrom the Faculty of Nutrition, Texas A&M University, College Station, Texas, USA

INTRODUCTION

Colon cancer is the second leading cause of death from cancer inthe United States today, and its development is highly responsive

to diet.1 With the important exception of the most recent summaryof data from the Nurse’s Study, which finds no relationship be-tween fiber intake and colon tumor incidence,2 most epidemiologicstudies have shown a protective effect.3 Clinical trials are ongoing,and the few that have been reported (with either a decrease incolonic cell proliferation or a decrease in polyp recurrence asendpoints) at best have shown only modest protective effects withfiber supplementation.4 In sharp contrast, almost every experimen-tal carcinogenesis study in rats has reported lower numbers oftumors with supplementation of specific fibers (in particular wheat

This study was supported by NIH CA 61750, CA59034, and AICR.

Correspondence to: Joanne R. Lupton, PhD, Faculty of Nutrition, 218Kleberg Building, Texas A&M University, College Station, TX 77843-2471, USA. E-mail: jlupton@tamu.edu

558 Lupton Nutrition Volume 16, Numbers 7/8, 2000