Malnutrition and Immunity

1. Malnutrition and Immunity BMB 505 – Advanced Nutrition and Nutritional Biochemistry Yearul Kabir (Handout # 3) Date: 21.01.2010

2. Nutrition and Infection • The response of a host to an infectious agent depends upon several factors. While the genetic constitution of the individual primarily determines the potential of the individual to produce adequate and appropriate immune responses which can act against the microbes, the dose and virulence of the microbes tend to determine the nature of the disease. • The interactions between the host and the microbes are also influenced by a number of environmental factors, nutritional status being one critical factor. • Disease manifestations emerge as a direct consequence of the organisms per se or because of the toxic products they secrete or release. • Less common disease mechanisms may emerge as secondary interactions of a host defensive mechanism with the invading organism or its products.

3. Nutrition and Infection… • A complex interactive battle occurs between the invading microorganisms and defensive mechanisms of the host. Metabolic and biochemical responses of the host contribute to these defensives, which eventually determine the outcome of each episode of infection. • Symptomatic infectious illness and even some asymptomatic ones are accompanied by direct or functional losses in the body content of many nutrients and by a redistribution in the body localization of others. • The magnitude of these changes is dependent on the severity and duration of an infection. • If the infectious process can be cured or eliminated naturally by host defensive mechanisms, lost body nutrients can then be reacquired and body stores reconstituted.

4. Nutrition and Infection… • This restoration may take a period of weeks to months. • If on the other hand, the infectious process is not eliminated and becomes subacute, chronic, or progressive, body composition becomes markedly altered and a new “relative equilibrium” of body nutrient balances emerges, but at a severely wasted level.

5. Host Defense Mechanisms • In order to prevent entry of pathogenic microorganisms into the body or to eliminate those that do gain access, the human and animal host possesses a variety of defensive mechanisms. • The nonspecific defenses are characterized by both passive and active components that respond to infections of any kind. In addition, more powerful immune defenses are triggered by antigenic components of specific single microorganisms. • Passive defensive components includes: • The anatomic barriers formed by skin, mucous membranes • Normal secretions of the body, including tears, saliva, gastric juice and mucus • Normal serum contains a number of proteins that serve as antimicrobial factors in host defense such as lysozyme, transferrin, complement.

6. Host Defense Mechanisms… • Active components of host defense can be subdivided into specific and non-specific defenses. • The non-specific components respond in a relatively similar manner to a large variety of different pathogenic microorganisms, including the production of phagocytic cells, and the synthesis of proteins such as interferon, lysozyme and the acute-phase reactants. • The antigenically specific responses are provided by the immune system and require a capacity for “memory”. • Specific immunity is generated by an interplay of both the humoral and cell-mediated arms of the immune system. • It is important to note that the function of all active host defensive mechanisms and many of the passive ones require an ongoing capacity of body cells to synthesize new proteins.

7. Host Defense Mechanisms… • For this reason, any nutritional deficit or imbalance that influences protein synthetic functions can lead in turn to functional impairment of some defensive mechanism and thus, generally, to a weakening of host resistance. • It is however over simplification to conclude that malnutrition always leads to an increased incidence of infectious diseases and to disease processes of increased severity. • In some instances, the malnourished state of the host makes it difficult for an invading microorganism to acquire certain nutrients from host tissues that the organism needs for its own growth and replication. In such a situation, the infectious process would be less severe than expected. • This phenomenon is seen most often in viral or parasitic diseases.

8. Host Defense Mechanisms… • Malnutrition does not have a uniform, across-the-board effect on all aspects of host defense. Rather, some components of the host’s defensive mechanisms are more resistant to malnutrition than are other components. • While PEM is the most common and important cause of immunologic dysfunction. A growing body of evidence indicates that isolated deficiencies of many single nutrients can also impair some aspect of host immunity. • In fact, excesses of some single nutrients, such as iron, zinc, ot vitamin E or imbalances among some nutrients, such as essential amino acid, can also cause a functional disruption of immune system components.

9. Host Defense Mechanisms… Nonspecific active components of host defense • Phagocytic cells, predominantly neutrophils and macrophages, are generally the first kind of host cell to interact with invading microorganisms or damaged host tissues. • When these cells become activated, they release hormone-like endogenous mediator substances that trigger generalized nonspecific host defensive reactions. • They stimulate hypothalamic centers to initiate fever and perhaps anorexia • They cause the liver to take up amino acids, zinc, and iron and initiate the synthesis of various enzymes, acute-phase reactant proteins and lipoprotein-triglyceride complexes for release into the plasma.

10. Host Defense Mechanisms… • These mediators also stimulate the bone marrow to manufacture and release additional phagocytic cells. • The immune system, especially its cell-mediated functions, is adversely affected by generalized PEM as well as by various forms of single nutrient abnormality. • Similarly, a number of these malnutritional states have an adverse effect on the function of phagocytic cells.

11. Nutritional Responses to Infection • Cells in the liver and lymphoid tissues rapidly increase their rates of synthesis of the proteins needed for host defensive mechanisms and the proliferation of phagocytic and lymphoid cells is speeded. • In order to support these anabolic requirements and to provide the increased fuels needed to maintain high metabolic rates in the presence of anorexia (loss of appetite for food) and a diminished food intake, catabolic processes are also accelerated. • Stored labile protein present in muscle fibers and somatic tissues serve to provide the require additional supply of amino acid substrate, thereby free for reutilization via numerous metabolic pathways in cells and tissues. • These are used for glucose production as well as for the synthesis of the new proteins required for host defense. • In fueling the increased metabolic activity, the body appears to increase its utilization of glucose. In contrast utilization of lipid fuels does not appear to be accelerated.

12. Hepatic Synthesis of Protein • The accelerated flux of free amino acids into the liver allows them to be used for two primary purposes, i.e., for the synthesis of new proteins or for the production of glucose. • Although infection does not alter the manner in which hepatic proteins are produced, but it has a profound effect on rates of protein synthesis and the types of protein being synthesized. • Information is not available as to how, or in some instances even why, certain hepatic proteins are selected for accelerated production. • The majority of newly synthesized hepatic proteins, however, are those classified as acute-phase reactants, a designation that matches their rapid increase in plasma during the acute phase of infectious or inflammatory diseases.

13. Hepatic Synthesis of Protein… • These acute-phase reactants are all glycoproteins, and include such diverse proteins as • Heptoglobin • Acid glycoprotein • Ceruloplasmin • C-reactive protein • Fibrinogen Each of these proteins has some role to play in the nonspecific aspects of host defense. Increases of some hepatic proteins (new protein molecules) may require decreases of others. Decline in plasma albumin conc. is perhaps the most consistently observed biochemical change during a wide variety of infectious diseases, which is assumed as a compensatory mechanisms associated with the increase in acute-phase reactant production.

14. Vitamins and Immune System • Most studies performed in experimental animals. • Animals with a low intake of vitamin B1 had a reduced production of antibodies and a decreased total number of lymphocytes. • Animals fed with a vitamin B2 deficient diet showed a reduced thymus weight, antibody production and a lower activity of macrophages. • Vitamin B6 deficiency impair humoral and cellular immunity more profoundly than did vitamin B1 and B2 deficiencies. • In animal studies, vitamin E supplementation has showed an improvement of the resistance against infectious organisms and of the humoral immune response. • The physiological role of antioxidants for achieving ‘optimal’ immune function is clearly demonstrated by the conc. of vitamin C in macrophages and neutrophils, which is about 150 times higher than in the surrounding plasma.

15. Malnutrition, Infection, and Immunity There is a complex three-way relationship between malnutrition, the immune system and infection, with malnutrition eliciting immune system dysfunctions which in turn promote increased vulnerability of the host to infection, and the latter intensifying the severity of malnutrition. The immune dysfunctions associated with malnutrition are referred to as Nutritional-Acquired Immune Deficiency Syndrome (NAIDS).

16. Characterization of Malnourished • Functional complement deficit • Diminished opsonic capacity of serum • Diminished avidity of antibody response • Inhibition of neutrophil and macrophage migration • Reduced intracellular killing capacity of phagocytic cells • Decreased secretory IgA (sIgA) production, and endocrine function adaptations such as • diminished synthesis of insulin and increased circulating levels of growth hormone and the glucocorticoids. Malnutrition alters all defense mechanisms including • anatomic barriers • cell-mediated immune (CMI) responses • phagocytic cell/microbicidal functions, and • humoral (antibody and complement responses) among many others.

17. Some of the immunological changes observed in malnourished individuals are summarized in table 1.

18. Table 1. Continuation

19. Effects of Malnutrition on Possible Defense Mechanisms • Malnutrition affects adversely various defense mechanisms in the human body • Antibody Formation: In experimental animals, deficiencies of various vitamins of B-complex, Vitamin A, Vitamin C and proteins have all been shown to interfere with antibody formation. • In man, antibody formation is low in deficiency of protein, pyridoxine, pantothenic acid and multiple factors associated with a grossly inadequate diet. • Phagocytic activity: Severe undernutrition or protein depletion in experimental animals leads to atrophy of liver, spleen, bone marrow and lymphoid tissue from which phagocytes originate. • There is also evidence indicating that deficiencies of vitamin A, ascorbic acid, pyridoxine, folic acid, thiamine and riboflavin reduce the activity of phagocytes.

20. Effects of Malnutrition on Possible Defense Mechanisms… • Tissue integrity: Dietary inadequacies decrease resistance of the tissues to infection by causing pathological changes in epithelial and other cells. • The gross epithelial lesions resulting from nutrient deficiencies include: • metaplastic hyperkeratosis due to lack of vitamin A • dermatitis, cheilosis and angular stomatosis resulting from ariboflavinosis • the characteristic dermatosis and mucosal atrophy of pellagra • spongy gums and subcutaneous hemorrhages of scurvy and • atrophy of skin and GI mucosa of severe protein deficiency

21. Effects of Malnutrition on Possible Defense Mechanisms… • Intestineal Flora: Changes in the normal intestinal flora induced by diet can influence a susceptibility to some intestinal pathogens. • in Kwashiorkor, there is a large increase in the total count of intestinal bacteria and a tendency for the bacteria of lower intestinal to appear in the upper intestinal tract, as in common with patients suffering from sprue. • Further, intestinal organisms which are known pathogenic in normal human subjects may become pathogenic in acute diarrhoeal diseases of malnourished children. • Resistance of Infection: Lysozymes which can destroy pathogenic microorganisms are excreted in tears and sweat. Their activity has been reported to be reduced in human subjects suffering from Vitamin A deficiency. • Rats suffering from deficiency of Vitamin A or B-complex have been reported to be more susceptible to diphtheria toxin than normal animals.

22. Effects of Malnutrition on Resistance to Infection • Some of the normal defense mechanisms of the body are impaired and do not function properly in the malnourished subject. • For example, children with Kwashiorkor were shown to be unable to form antibodies to either typhoid vaccine or diphtheria toxoid; their capacity to do so was restored after protein therapy. • Another defense mechanism that has been studied in relation to nutrition is that of leucocytosis (increased production of WBC) and phagocytic activity (destruction of bacteria by white corpuscles). Children with Kwashiorkor show a lower than normal leucocyte response in the presence of an infection. • Perhaps of greater importance is the reduced phagocytic efficiency in malnourished subjects of the polymorphonuclear leucocytes that are part of the fight against invading bacteria. • When malnutrition is present, these cells appear to have a defect in their intracellular bactericidal (bacteria-destroying) capacity.

23. Effects of Infection on Nutritional Status • Infection affects nutritional status in several ways: • Protein: Most important of these is that bacterial and some other infections lead to an increased loss of nitrogen from the body. • First demonstrated in serious infections such as typhoid fever, but it has subsequently been shown in much milder infections such as otitis media, tonsillitis, chicken pox and abscesses. Also occur in common cold, fever, tuberculosis, rheumatoid arthritis, pneumonia, measles, etc. • Nitrogen is lost by several mechanisms. The principal one is probably increased breakdown of tissue protein and mobilization of amino acid, especially from the muscles. • The nitrogen is excreted in the urine and is evidence of a depletion of body protein from muscles.

24. Effects of Infection on Nutritional Status… • In children whose diet is marginal in protein content, or those who are already protein depleted, growth will be retarded during and after infections. • Recovery requires increased intake of protein, above maintenance levels, in the post-infection period. • Calorie: Anorexia or loss of appetite is another factor in the relationship between infection and nutrition. • Infections, especially if accompanied by a fever, often lead to loss of appetite and therefore to reduce food intake. • Some infectious diseases commonly cause vomiting with the same result. • Gross underfeeding of sick children for long periods is one of the most important causes for the wide prevalence of PEM among preschool children in the developing countries.

25. Effects of Infection on Nutritional Status… • In children whose diet is marginal in protein content, or those who are already protein depleted, growth will be retarded during and after infections. • Recovery requires increased intake of protein, above maintenance levels, in the post-infection period. • Calorie: Anorexia or loss of appetite is another factor in the relationship between infection and nutrition. • Infections, especially if accompanied by a fever, often lead to loss of appetite and therefore to reduce food intake. • Some infectious diseases commonly cause vomiting with the same result. • Gross underfeeding of sick children for long periods is one of the most important causes for the wide prevalence of PEM among preschool children in the developing countries.

26. Effects of Infection on Nutritional Status… • In children whose diet is marginal in protein content, or those who are already protein depleted, growth will be retarded during and after infections. • Recovery requires increased intake of protein, above maintenance levels, in the post-infection period. • Calorie: Anorexia or loss of appetite is another factor in the relationship between infection and nutrition. • Infections, especially if accompanied by a fever, often lead to loss of appetite and therefore to reduce food intake. • Some infectious diseases commonly cause vomiting with the same result. • Gross underfeeding of sick children for long periods is one of the most important causes for the wide prevalence of PEM among preschool children in the developing countries.

27. Effects of Infection on Nutritional Status… • Vitamins: Blood levels of vitamin A are reduced in several infections. • Xerophthalmiaand Keratomalacia have been shown to be precipitated by infections in malnourished children receiving a diet deficiency in vitamin A. • Minerals: Hookworm infection causes enough blood loss to cause anemia even when iron intakes are normal. Malaria causes haemolysis of RBC and hence leads of anemia. • Tuberculosis increase losses of calcium and phosphorus in the urine and feces. • Diarrhoeal diseases interfere in the absorption of dietary minerals and causes losses of Na, K, Cl, Ca and P from the body.

28. Effects of Infection on Nutritional Status… • Lipids: An increase in liver fat and in the fat content of the feces has been observed in influenza and pneumonia and probably occurs in many other infections. • Absorption of fat is also decreased in intestinal infections which provoke diarrhea. • Carbohydrates: Marked reduction in blood glucose levels has been reported to occur in many infectious diseases. This may probably be secondary to reduced calorie intake and low glycogen stores in liver.

29. Effect of Infection on Growth and Development • Several investigations have shown that frequent occurrence of infectious diseases affects adversely the growth rate of children. • Children not suffering from any illness, were once inch taller than those who had experienced ‘severe’ illness. • Many investigator in the developing countries have reported that children suffering frequently from measles, chickenpox or diarrhea show marked loss of body weight and body fat and wasting of muscle as compared with children from the same locality not suffering from any illness.

30. Nutrition and Immunodeficiency Disorders • What is Immunodeficiency Disorders? • Immunodeficiency disorders refers to a group of disorders in which the immune system does not function normally. • Our bodies’ immune cells attack and kill what they see as foreign invaders, usually bacteria, viruses, and fungi. When the immune system does not work properly, a person is more likely to suffer from frequent and longer lasting infections, often from organisms that don’t normally make most people sick. • Immunodeficiency disorders occur when the body's immune response is reduced or absent. • Congenital immunodeficiency is present at birth. • Another type of immunodeficiency disorder is called acquired immunodeficiency, which develops later in life.

31. Causes, incidence, and risk factors • Immune system disorders occur when the immune system does not fight tumors or harmful substances as it should. The immune response may be over active or under active. • Immunodeficiency disorders may affect any part of the immune system. Most commonly, such a condition occurs when specialized white blood cells called T or B lymphocytes (or both) do not work as well as they should, or when your body doesn't produce enough antibodies. • Malnutrition, particularly with lack of protein, and many cancers, may also cause immunodeficiency. • Persons who have had their spleen removed are at higher risk for from certain bacteria that the spleen would normally help fight. • Patients with diabetes are also at higher risk for certain infections. • Increasing age reduces the effectiveness of the immune system to some degree. Immune system tissues (particularly lymphoid tissue such as the thymus) shrink, and the number and activity of white blood cells drop.

32. Conditions and diseases that can result in an immunodeficiency disorder • Ataxia-telangiectasia • DiGeorge syndrome • Chediak-Higashi syndrome • Job syndrome • Leukocyte adhesion defects • Panhypogammaglobulinemia • Bruton disease • Congenital agammaglobulinemia • Selective deficiency of IgA • Combined immunodeficiency disease • Wiscott-Aldrich syndrome • Complement deficiencies • Hypogammaglobulinemia

33. Symptoms, Signs and Tests • The symptoms vary with the specific disorder. • Signs and tests • Persistent, recurrent infections, or severe infection by microorganisms that do not usually cause severe infection, may be a sign that an immunodeficiency disorder is present. Other signs include: • Poor response to treatment • Delayed or incomplete recovery from illness • Certain types of cancers (such as Kaposi’s sarcoma or non-Hodgkin's lymphoma) • Certain infections (such as pneumocystis carinii pneumonia or recurrent fungal yeast infections)

34. Symptoms, Signs and Tests … • Tests used to help diagnose an immunodeficiency disorder may include: • White blood cell count • Antibody/immunoglobulin levels • T (thymus derived) lymphocyte count • Complement levels or other measurements of immune-response components

35. Causes • Congenital immunodeficiency disorders are caused by a genetic abnormality, which is often X-linked. That is, boys are more likely to be affected than girls. As a result, about 60% of affected people are male. • Acquired immunodeficiency disorders may result from almost any prolonged serious disorder. • Examples are cancer, blood disorders (such as aplastic anemia, leukemia, and myelofibrosis), kidney failure, diabetes, liver disorders, and spleen disorders. • Diabetes can result in an immunodeficiency disorder because white blood cells do not function well when the blood sugar level is high. • Infections can also cause immunodeficiency disorders. • Human immunodeficiency virus (HIV) infection results in acquired immunodeficiency syndrome (AIDS), the most common severe acquired immunodeficiency disorder.

36. Causes… • Undernutrition: When undernutrition causes weight to decrease to less than 80% of recommended weight, the immune system is usually impaired. A decrease to less than 70% usually results in severe impairment. Use of certain drugs called immunosuppressants may result in an acquired immunodeficiency disorder. These drugs are intentionally used to suppress the immune system. • For example, immunosuppressants are used to prevent rejection of a transplanted organ or tissue, and corticosteroids, a type of immunosuppressant, are used to suppress inflammation due to various disorders. • However, immunosuppressants also suppress the body's ability to fight infections and perhaps to destroy cancer cells. • Chemotherapy and radiation therapy can also result in immunodeficiency disorders.

37. Dietary Modification in Infection and Fever General Dietary Consideration The diet in fevers and infections depends upon the nature and severity of the pathologic conditions and upon the length of the convalescence. In general it should meet the following requirements: • Energy: The needs for energy are increased by 10 to 30% during and after acute infections. • The caloric requirement may be increased as much as 50% in case of high fevers lasting for a longer period and the tissue destruction is great. • However, due to fever, the patient’s appetite is poor and digestion may be hampered, hence the maximum number of calories that can be tolerated by him should be given.

38. Dietary Modification… • Protein: A high protein diet supplying about 1.25 to 1.5 g protein per kg body weight should be fed. • About 100 g protein or more is prescribed for the adult when a fever is prolonged. • Protein supplements which can be incorporated in beverages may be given • Carbohydrates: They should be high and as liberal as possible. • Glycogen stores are replenished by a liberal in take of carbohydrates. • Any sugars such as glucose, corn syrup, and cane sugar may be used. • It is advisable to add glucose in all liquids and fruit juices given to the patient since it is well tolerated in large amounts and is easily assimilated by the body.

39. Dietary Modification… • Fats: The energy intake may be rapidly increased through the judicious use of fats, but fried foods and rich pastries may retard digestion unduly. • Minerals: Loss of the two electrolytes, sodium and potassium, should be replaced. • A sufficient intake of sodium in the form of sodium chloride is accomplished by the use of salty broth and soups and by liberal sprinklings of salt on food. • Generally speaking, foods are a good source of potassium, but a limited food intake might result in potassium depletion whenever fever is high and prolonged. • Thus, Potassium, which is also needed in greater amounts, should be given through fruit juices and milk which are relatively good sources of potassium.

40. Dietary Modification… • Requirement of zinc and iron increases since both are involved in the immune process. Infected patients show a decreased blood zinc level because of its migration to tissues and organs. • Zinc excretion in urine also increases. • Iron losses occur due to increased destruction of the red blood cells. • Iron supplementation is often required to correct the anemia that results from some parasite infections.

41. Dietary Modification... • Vitamins: Vitamin requirements are increased if infection is accompanied by swelling and nacrosis of the tissue. • Fevers apparently increase the requirements for vitamin A and ascorbic acid, just as the B-complex vitamins are needed at increased levels proportionate to the increase in calories; that is, 0.5 mg thiamin, 0.6 mg riboflavin, and 6.6 mg niacin equivalents per 1000 additional kcal. • Oral therapy with antibiotics and drugs interferes with synthesis of some B-complex vitamins by intestinal bacteria, thus necessitating a prescription for vitamin supplements for a short time. • All vitamins may be given as supplements to the patient.

42. Dietary Modification… • Fluid: The fluid intake must be liberal to compensate for the losses from the skin and to permit adequate volume of urine for excreting the wastes. • From 2500 to 5000 ml daily are necessary, including beverages, soups, fruit juices, and water. • Texture and Consistency of the Diet: Soft texture and fluid to semi-solid consistency are desirable to promote appetite and help the patient to consume a diet which is nutritionally adequate. • Ease of digestion: Bland, readily digested foods should be used to facilitate digestion and rapid absorption.

43. Dietary Modification… • Intervals of feeding: Small quantities of food at intervals of two to three hours will permit adequate nutrition without overtaxing the digestive system at any one time. • Generally, 6-8 feedings should be sufficient. • With improvement, many patients consume more food if given three meals and a bedtime feeding.

44. Diet in Fevers of Short Duration • The duration of many fevers has been shortened by antibiotic and drug therapy, and nutritional needs are usually met without difficulty. • During an acute fever the patient’s appetite is often very poor, and small feedings of soft or liquid foods should be offered at frequent intervals. • Sufficient intake of fluids and salt is essential. • If the illness persists for more than a few days, high-protein, high-calorie foods will need to be emphasized.

45. Diet in Typhoid • Fever in typhoid is of a long duration. • The rise in temperature is very high, thus causing significant damage to the nutritional status of the person. • Antibiotic therapy helps a lot to curb the fever but however short the period may be, protein losses are very high, glycogen stores of the body are depleted to a very large extent and the water balance too may be affected severely. • The antibiotic therapy also kills the beneficial symbiotic bacterial flora of the intestine. • In this disease the intestines are the worst affected part of the body.

46. Dietary Modification in Typhoid • Dietary modifications are similar to those given in case of fevers of short duration. • However, caution must be exercised in preventing inclusion of irritating dietary fibers. • All whole-grain cereals and cereal products, leafy vegetables, raw vegetables and fruits should be eliminated from the diet. • Tender meat, fish and poultry, potatoes, soft-cooked vegetables and simple preparations restricting the use of excessive fat and spices is advised.

47. Dietary Modification in Tuberculosis • The energy needs are markedly increased due to wasting of tissues. • A diet providing 3000 to 3500 kcals, about 75-100 g protein and large amounts of calcium and iron (if there is bleeding) and Vitamins A and C are advised for fast recovery and quicker tissue regeneration. • B-complex vitamins especially pyridoxine and folic acid are prescribed in larger amounts. This is so because the drug, Isoniazid, which is commonly used in the treatment of tuberculosis is an antimetabolite of pyridoxine and prevents folate-dependent reactions.

48. Summary: Dietary Modification in Infection and Fevers • Precipitated infection, however mild it may seem, can play havoc on the body resources, increasing the need for several nutrients, especially fluids, energy, proteins, vitamins and electrolytes. • In case the infection is accompanied by fever, it adds to the nutritional stress since fever increases the metabolic rate enhancing the energy need. • Fevers of either long or short durations are caused by influenza, typhoid, tuberculosis, malaria, etc. • Easily digestible, nutritionally-rich diet, divided into small servings, taken at frequent intervals during the day is advisable under these conditions.

49. Recommended Books • Nutritional Biochemistry and Metabolism with Clinical Applications. Edited by Maria C. Linder. Lsevier Science Publishing Company Inc., New York, 1985. • Textbook of Human Nutrition. Editors: Mahtab S. Bamji, N. PralhadRao and Vonodini Reddy. Oxford & IBH Publishing Co. Pvt. Ltd., New Delhi, 1996. • Advanced Textbook on Food and Nutrition. Volume I, By M. Swaminathan, 1998.