Introduction to Human Nutrition 2nd Edition ( PDFDrive )

in. temp Forms Heat resistance (a) Gram stain (a) Source 328 Introduction to Human Nutrition pt. temp spores (b) Aerobic/ (b) Associated foodsb in. pHa Yes Heat-sensitive, Min. Awb but can form anaerobic (a) Soil, dust and 0°C Yes heat-resistant vegetation 0–35°C spores (D121 = (a) Gram 3 0.03–2.35 min) positive (b) Cooked rice, cereals 95 and cereal-based Emetic toxin: (b) Facultative products, herbs and pI extremely heat anaerobe spices 0°C resistant (can 0–40°C withstand 6 121°C for 90 min) 94 p II Toxin: destroyed by (a) Gram (a) Soil, sediment, 3°C 5 min at 85°C positive intestinal tract of fish 5–37°C and mammals 0 Group I (b) Obligate 97 Spores: anaerobe (b) Canned foods, D100 = 25 min smoked and salted D121 = <0.001 min fish, honey 0.1–0.2 min Group II Spores: D100 < 0.1 min D121 = <0.001 min

Staphylococcus Food handlers play a major (a) 1–6 h (a) Nausea, (a) 7° aureus role in transmission. S. (b) 1–2 vomiting, (b) 35 aureus is carried in nose/ abdominal pain (c) 4.5 throat of ~40% of healthy days and diarrhea (d) 0.8 individuals and can be easily transferred to food (b) <1.0 μg toxin via the hands. Most (>105 cells/g implicated foods have been needed to ready-to-eat foods that produce have been contaminated sufficient toxin) by poor handling practices and stored at incorrect temperatures, allowing S. aureus to grow to levels (>105 cells/g) that will produce sufficient heat- stable staphylococcal toxin a Under otherwise optimal conditions; limits will vary according to strain, temperature, type of acid b Not an exhaustive list. Min., minimum; Opt., optimal; Aw, water activity.

°C No Toxin: heat (a) Gram (a) Exposed skin lesions, 5–37°C resistant (able positive nose, throat and 5 to withstand hands 83 boiling for up (b) Facultative to 30 min) anaerobe (b) Generally foods of animal origin that have been physically handled and have not received a subsequent bactericidal treatment (in the case of pH), solute (in the case of Aw), and other factors. Food Safety 329

Table 14.2 Characteristics of food-borne bacterial infections Food-borne illness Bacteria Comment (a) Onset (a) Symptoms Bacillus cereus (b) Duration (b) Infectious dose Vegetative cells are inactivated (a) 8–16 h (a) Abdominal pain and (diarrheal) by normal cooking (b) 12–14 h temperatures; however, diarrhea Clostridium spores are quite heat (a) 12–18 h (b) >105 cells per fringens resistant. The diarrheal (can be enterotoxin is produced 8–22 h) (a) Diarrhea and severe when spores germinate in abdominal pain the small intestine af ter (b) 24 h consumption of (b) >106 cells/g contaminated food Illness results from consumption of food containing high numbers of cells (>106/g) followed by enterotoxin production in the large intestine. When contaminated food is cooked, sporulation is induced. As the food cools, the spores germinate and vegetative cells continue to multiply, unless the food is cooled quickly and stored under refrigerated conditions

(a) Min. temp Heat resistance (a) Gram stain (a) Source 330 Introduction to Human Nutrition (b) Opt. temp (b) Aerobic/ (b) Associated foodsb (c) Min. pHa Heat-sensitive, but (d) Min. Awb forms heat- anaerobic (a) Soil and dust resistant spores (b) Meat, milk, (a) 10°C (D121 = (a) Gram positive (b) 30–35°C 0.03–2.35 min) (b) Facultative vegetables, fish and (c) 4.3 soups (d) 0.95 anaerobe (a) 15°C Heat-sensitive, but (a) Gram positive (a) Soil and animal (b) 43–45°C forms heat- (b) Obligate feces (c) 5.0 resistant spores (d) 0.95 (D95 = 1.3–2.8 min) anaerobe (b) Meat, poultry, gravy, dried and precooked foods

Campylobacter C. jejuni is one of the most (a) 2–5 days (a) Moderate to severe common causes of bacterial (b) 1–7 days diarrhea, sometimes Verotoxigenic food poisoning in many bloody diarrhea. Escherichia coli industrialized countries. (a) 1–6 days Severe abdominal (VTEC) Although campylobacters (b) 4–6 days pain. Vomiting is rare are fragile organisms, and Complications are Listeria do not survive or multiply (a) Up to 10 uncommon, but monocytogenes very well on foods, the low weeks (FG: include bacteremia, infectious dose means 20–27 h) reactive arthritis and that a small level of Guillain–Barré contamination may result in (b) Days to syndrome illness. Compared with weeks (FG: other food-borne bacteria self- (b) 500 cells with low infectious doses, limiting, relatively few outbreaks usually 1–3 (a) Diarrhea and severe have been identified days) abdominal cramps, bloody diarrhea VTEC is of considerable (hemorrhagic colitis), concern due to the severity approx. 5% (mostly of illness. The organism is children) develop easily killed by cooking, but hemolytic uremic the low infective dose syndrome (HUS) means that foods must be cooked thoroughly and (b) 10–100 cells protected from (a) Flu-like symptoms, cross-contamination meningitis and/or L. monocytogenes causes septicemia. While serious illness in individuals pregnant women ma with impaired cell-mediated experience a mild flu immunity. Highly susceptible like illness, infection individuals include pregnant may result in women, neonates, miscarriage, stillbirth older people and or birth of a severely immunocompromised ill infant. (FG: fever, individuals. The organism is watery diarrhea, also reported to cause nausea, headache febrile gastroenteritis (FG) and pains in joints in healthy persons. Foods and muscles) associated with (b) Unknown transmission tend to be processed, ready-to-eat foods, with long shelf-lives (>5 days) stored at refrigeration temperatures

(a) 32°C Heat-sensitive (a) Gram (a) Chickens, birds, (b) 42–43°C negative cattle, flies, and (c) 4.9 water (d) 0.98 (b) Fastidious e. microaerophile (b) Undercooked chicken, raw milk, beef, pork, lamb, shellfish, and water (a) 7°C Heat-sensitive (a) Gram (a) Cattle, sheep, pigs, (b) 37°C negative deer (c) 4.5 (d) 0.97 (b) Facultative (b) Undercooked beef anaerobe burgers, raw milk, (a) 0°C Heat-sensitive salad vegetables, (b) 30–37°C (a) Gram positive and unpasteurized (c) 4.3 (b) Facultative apple juice (d) 0.90 anaerobe (a) Soil, improperly made silage ay u- (b) Fresh sof t cheeses, raw milk, deli meats, pâté, hot dogs, raw vegetables, ice cream, and seafood y Food Safety 331

Table 14.2 Continued Food-borne illness Bacteria Comment (a) Onset (a) Symptoms (b) Duration (b) Infectious dose Salmonella Although there are approx. (a) Usually (a) Fever, abdominal 2400 different Salmonella 12–36 h, pain, diarrhea, Vibrio cholerae serotypes only a small but may be nausea and serogroup number account for most 6–72 h sometimes vomiting. non-O1 human infections, with Can be fatal in older S. Typhimurium and S. (b) 2–5 days people or those with Vibrio Enteritidis predominating. weakened immune parahaemolyticus Undercooked food from system infected food animals is most commonly implicated. (b) ~106 cells Egg-associated salmonellosis is an (a) 1–3 days (a) Diarrhea, abdominal important public health (b) Diarrhea cramps, fever, some problem vomiting, and nausea lasts 6–7 Vibrio cholerae non-O1 is days (b) >106 cells related to V. cholerae O1 (the organism that causes (a) 12–24 h (a) Diarrhea, abdominal Asiatic or epidemic cholera), (b) <7 days cramps, nausea, but causes a disease vomiting, headache, reported to be less severe fever, chills than cholera. It has been generally believed that (b) >106 cells water was the main vehicle for transmission, but an increasing number of cases have been associated with food V. parahaemolyticus can be considered to be the leading cause of seafood- borne bacterial gastroenteritis. It is frequently isolated from fish from both marine and brackish-water environments

(a) Min. temp Heat resistance (a) Gram stain (a) Source 332 Introduction to Human Nutrition (b) Aerobic/ (b) Associated foodsb (b) Opt. temp anaerobic (c) Min. pHa (a) Gram (a) Water, soil, animal (d) Min. Awb feces, raw poultry, negative raw meats, and raw (a) 7°C Heat-sensitive (b) Facultative seafood (b) 35–37°C (c) 4.0 anaerobe (b) Raw meats, poultry, (d) 0.93 eggs, raw milk and (a) Gram other dairy products, h negative raw fruits and vegetables (e.g., l (a) 10°C Heat-sensitive (b) Facultative alfalfa sprouts and (b) 37°C anaerobe melons) a (c) 5.0 (a) Costal waters, raw (d) 0.97 oysters (b) Shellfish l (a) 5°C Heat-sensitive (a) Gram (a) Costal and (b) 37°C negative estuarine waters, (c) 4.8 raw shellfish (d) 0.94 (b) Facultative anaerobe (b) Fish and raw shellfish

Vibrio vulnificus V. vulnificus is considered to (a) 16 h (a) Wound infections, be one of the most invasive (b) Days to gastroenteritis, Yersinia and rapidly lethal of human primarily septicemia enterocolitica pathogens. Infection starts weeks with a gastrointestinal (b) Unknown in healthy illness, and rapidly (a) 3–7 days individuals but in progresses to a septicemic (b) 1–3 weeks predisposed <100 condition. It is mostly cells associated with the consumption of raw oysters. (a) Diarrhea, abdominal Human infections are rare, pain and fever. but those at most risk either Intestinal pain, have underlying illnesses or especially in young are immunocompromised adults, may be confused with Y. enterocolitica is appendicitis psychrotrophic and known to be quite resistant to (b) Unknown freezing, surviving in frozen food for extended periods. The organism is present in a wide range of animals, especially pigs. Milk and pork have been implicated in outbreaks, especially in countries where pork is eaten raw or undercooked a Under otherwise optimal conditions; limits will vary according to strain, temperature, type of acid b Not an exhaustive list. Heat-sensitive: cells destroyed by typical cooking temperatures; Min.: minimum; Opt.: optimal; Aw:

(a) 8°C Heat-sensitive (a) Gram (a) Coastal waters, (b) 37°C negative sediment, plankton, (c) 5 shellfish y (d) 0.96 (b) Facultative anaerobe (b) Oysters, clams, crabs l (a) –1.3°C Heat-sensitive (a) Gram (a) Wide range of (b) 25–37°C negative animals (e.g., pigs, (c) 4.1 dogs, cats) and (d) 0.96 (b) Facultative water anaerobe (b) Undercooked pork, raw milk and water (in the case of pH), solute (in the case of Aw) and other factors. water activity. Food Safety 333

334 Introduction to Human Nutrition Table 14.3 Characteristics of the illnesses caused by hepatitis A and norovirus Hepatitis A (picornavirus) Norovirus (calicivirus) Properties Particles are featureless spheres 28 nm in diameter, single- Particles are spheres 25–35 nm in diameter, single-stranded RNA Infection stranded RNA coated with protein coated with protein that has characteristic cupped surface Illness depressions Infection via intestine to liver, incubation period 15–20 Shedding days (mean 28 days) Infection of intestinal lining, incubation period 24–48 h Diagnosis Immunity Illness from immune destruction of infected liver cells: Nausea, vomiting, diarrhea, etc., lasting for 24–48 h fever, malaise, anorexia, nausea, abdominal discomfort, often followed by jaundice; severity tends to increase During illness (in vomitus and feces), possibly 7 days after onset with age: ranges from unapparent infection to weeks of debility, occasionally with permanent sequelae Detection of virus in stool ELISA or PCR or of antibody against the virus in patient’s blood serum; no standard methods, reagents Shedding of virus peaks during the second half of the not readily available for most agents incubation period (10–14 days), usually ends by 7 days after onset of jaundice Apparently transient Based on detection of IgM class antibody. Hepatitis A virus in the patient’s blood serum (kits available) Immunity is durable (possibly lifelong) after infection ELISA, enzyme-linked immunosorbent assay; IgM, immunoglobulin M; PCR, polymerase chain reaction. Exposure is by contact with infected individuals or food from a common supplier occurred in Osaka, fecally contaminated water or other materials. Shell- Japan, in 1991, affecting 4700 teachers and pupils fish (bivalve molluscs) have been the predominant from 14 schools in the city. food vehicle. Shellfish beds may frequently become contaminated with human feces from sewage dis- Rotaviruses charges. Aerosolization of vomitus-containing virus particles has been proposed as another mode of trans- Serogroup A rotaviruses are the single most impor- mission of the virus and may also be a source of food tant cause of infantile gastroenteritis worldwide, contamination. Sensitive detection assays have now affecting an estimated 130 million infants and causing revealed that shedding of the virus in feces may con- 873 000 deaths every year. The rotavirus genome tinue for up to a week after the illness subsides. consists of 11 segments of double-stranded RNA surrounded by a double-shelled viral capsid. When Astroviruses examined by electron microscopy, the double-shelled particles resemble a wheel-like structure morphologi- Under the electron microscope, astroviruses appear as cally (Latin rota, wheel). The incubation period of the small, round viruses that have surface projections illness is 1–3 days, and the illness is characterized by resembling a five- or six-pointed star (Greek astron, fever, vomiting, and diarrhea. Although the majority star). The illness differs from the norovirus in that the of rotavirus infections involve infants, outbreaks of incubation period is longer (3–4 days), the duration food-borne, and water-borne disease affecting all age of illness is longer (often lasting for 7–14 days), and groups have been reported, albeit infrequently. vomiting is less common, with diarrhea being the predominant symptom. In addition, the very young Other viruses (<1 year) appear to be the most susceptible group, whereas norovirus affects all age groups. Astrovirus Picornaviruses other than hepatitis A can also be outbreaks have been reported to occur in crèches, transmitted by the food-borne route. Polioviruses are schools, hospital wards, and nursing homes, but in transmitted by food but virulent strains of this agent many cases there was no well-defined mode of trans- are now extremely rare. Coxsackie virus and echovi- mission. One large outbreak linked to contaminated rus have been associated with food-borne outbreaks, but data are limited. Hepatitis E has been linked to a

Food Safety 335 number of water-borne outbreaks but there has been no association with food. One food-borne outbreak of parvovirus linked to consumption of cockles has been reported. 14.5 Food-borne parasites Food-borne parasitic diseases are a major public Figure 14.1 Life cycle of Diphyllobothrium latum. health problem affecting millions of people, predomi- nantly in nonindustrialized countries. The incidence the consumption of raw, undercooked, or otherwise of parasitic disease associated with the consumption underprocessed freshwater fish or crustaceans con- of foods of animal origin has declined in industrial- taining the infective stages (metacercariae) of these ized countries in recent years, where improvements in parasites. Table 14.4 summarizes the distribution, animal husbandry and meat inspection have led to the principal reservoirs, and freshwater fish or crus- considerable safety and quality gains. The situation in taceans involved in the transmission of these parasites nonindustrialized countries is very different, in that in the food chain. The most important parasites with these diseases are associated with poor standards of respect to the numbers of people affected are species sanitation and hygiene, low educational standards, of the genera Clonorchis, Opisthorchis, and Paragoni- and extreme poverty. mus. The diseases caused by food-borne trematodes include cholangiocarcinoma, gallstones, severe liver Parasites are organisms that live off other living disease, and gastrointestinal problems. organisms, known as hosts. They may be transmitted from animals to humans, from humans to humans, Nematodes or from humans to animals. Food-borne parasitic disease occurs when the infective stages of parasites The food-borne roundworms of primary importance are eaten in raw or partially cooked protein foods, or in humans belong to the phylum Nematoda and are in raw vegetables and fruits that are inadequately known as nematodes. Undercooked or raw fishery washed before consumption. These organisms then products and pork meat are the usual foods live and reproduce within the tissues and organs of involved. infected human and animal hosts, and are often excreted in feces. The parasites involved in food-borne Where fishery products are the food vector, the disease usually have complex life cycles involving one definitive hosts of roundworms causing disease in or two intermediate hosts (Figure 14.1). The food- humans are piscivorous marine mammals such as borne parasites known to cause disease in humans are seals. Marine invertebrates and fish are the two inter- broadly classified as helminths (multicellular worms) mediate hosts and humans are infected when they and protozoa (single-celled microscopic organisms). consume raw or minimally processed products. Fish These include the major helminthic groups of trema- are the secondary hosts and are infected when they todes, nematodes, and cestodes, and some of the consume the invertebrate primary host or fish that are emerging protozoan pathogens, such as cryptospo- already infected. There are many species of nematodes ridia and cyclospora. The illnesses they can cause and a very large number of species of fish, worldwide, range from mild discomfort to debilitating illness and that are known to act as intermediate hosts. The most possibly death. common species of nematode causing disease in humans is Anisakis simplex, sometimes referred to as These infections occur endemically in some 20 countries, where it is estimated that over 40 million people worldwide, mainly in eastern and southern Asia, are affected. Of major concern are the fish-borne trematode infections. The trematode species con- cerned all have similar life cycles involving two inter- mediate hosts. The definitive host is man and other mammals. Food-borne infection takes place through

Table 14.4 Food-borne trematode infections Parasite Distribution Principal reservoirs Liver flukes (other than humans) Clonorchis sinensis Widespread in China, Taiwan, Macao, Japan, Korea and Vietnam. Dogs, cats, and many other Opisthorchis felineus Migrants to other countries found species of fish-eating to be infected; cases in Hawaii mammals Opisthorchis attributed to consumption of fish viverrini imported from China Cats, dogs, and other mammals that eat fish or Commonwealth of Independent fish waste States (CIS), eastern and central Europe Dogs, cats, fishing cats (Felis viverrina), and Laos and north-eastern Thailand other mammals that feed (Mekong River basin) on fish and fish waste Faciola hepatica Europe, the Middle East, the Far East, Sheep, cattle Africa, Australia, USA Intestinal flukes Dogs, cats, jackals, foxes, Heterophyes Mediterranean basin, especially Egypt pelicans, hawks, and and eastern Asia black kite heterophyes Metagonimus Eastern and southern Asia Dogs, cats, pigs, and fish- yokogawai and eating birds related species

Food involved in Disease 336 Introduction to Human Nutrition transmission to humans The liver flukes, Opisthorchis viverrini, O. felineus Many species (c. 110) of freshwater and Clonorchis sinensis, are biologically fish, mainly Cyprinidae, e.g., carp, similar, food-borne trematodes that chronically roach and dace, most important infect the bile ducts and, more rarely, the being Pseudorasbora parva. pancreatic duct and gallbladder of humans Metacercariae in fish muscles and other mammals Freshwater fish of family Cyprinidae. Inflammation of the bile ducts which eventually Metacercariae in muscle and leads to fibrosis subcutaneous tissue The parasite can irritate the lining of the small Some 10 species of freshwater fish intestine, resulting in diarrhea and abdominal including Puntius orphoides and pain. In some instances the lining of the small Hampala dispar intestine breaks down, and the eggs produced by the parasite enter the bloodstream. Once in Metacercariae in fish muscles the bloodstream the eggs can be carried to other organs where they can cause significant Brackish water and freshwater fish, pathology, especially in the liver, heart, and especially mullet (Mugil spp.), brain Tilapia, and others. In Japan, species of fish genera Similar to Heterophyes heterophyes Acanthogobius and Glossogobius also involved. Metacercariae in muscle and skin Freshwater fish, e.g., sweetfish (Plecoglossus altivelis), dace (Tribolodon hakonensis), trout, and whitebait. Metacercariae in gills, fin, or tail

Nanophyetus spp. Eastern Siberia (mountain tributaries Dogs, cats, rats (?), and of Amur River) and parts of badgers Spelotrema Sakhalin peninsula, north-western brevicaeca USA Sea birds Cats, dogs, and fish-eating Haplorchis spp. Philippines Fasciolopsis buski birds Eastern and southern Asia Pigs Oriental countries Lung fluke Siberia, west Africa (Nigeria, Domestic and wild Paragonimus Cameroon), the Americas (Ecuador carnivora that feed on to USA), Japan, Korea, Thailand, crustaceans westermani and Laos, China related species in Asia, Africa and the Americas Based on data from Food Control, 6, Abdussalam et al., Food safety measures for the control of

Salmonid and other fish. Nanophyetiasis Metacercariae in muscles, fins, Diarrhea, usually accompanied by increased and kidneys numbers of circulating eosinophils, abdominal Crustaceans, amphipods, isopods, discomfort and nausea. Sometimes and brachyures asymptomatic Fish, frogs, and toads. Most infections are light and asymptomatic. Metacercariae in muscle Heavy infections show symptoms of diarrhea, Uncooked contaminated water plants abdominal pain, fever, ascites, anasarca, and intestinal obstruction such as water cress Freshwater and brackish water Paragonimiasis crabs (Eriocheir, Potamon, Parathelphusa), crayfish and shrimps. Metacercariae in muscles, gills, liver (hepatopancreas), and cardia region. Wild boar meat suspected as a source of infection f food-borne trematode infections, page 9, copyright 1995 with permission from Elsevier. Food Safety 337

338 Introduction to Human Nutrition the herringworm. The other species involved in anisa- nourishment. Infections can be prevented by sanitary kiasis in North America, Europe, and Japan is Pseudo- disposal and treatment of human waste and by terranova decipiens (the codworm or sealworm). thorough cooking and freezing of contaminated pork and beef. Nematodes are commonly present in fish caught in the wild, most frequently in the liver and belly cavity, Protozoa but can also occur in the flesh. Anisakiasis is an uncommon disease because the parasite is killed by The protozoal human parasites are unicellular organ- heating (55°C for 1 min), and by freezing (−20°C for isms that colonize the intestinal epithelium and form 24 h). There is a risk of illness from fishery products cysts. These are excreted and may survive for long consumed raw, for example sushi, or after only mild periods in the environment. There are five genera of processing, such as salting at low concentrations or concern in foods: Giardia, Entamoeba, Toxoplasma, smoking. Many countries now require that fish used Cyclospora, and Cryptosporidium. for these mildly processed products be frozen before processing or before sale. Table 14.5 summarizes the distribution, principal reservoirs and route of transmission of these parasites Trichinella spiralis is the cause of trichinosis in in the food chain. humans. This most commonly results from the con- sumption of contaminated raw or undercooked pork 14.6 Transmissible spongiform or pork products. Since the mid-1980s outbreaks have encephalopathies and food been associated with raw and undercooked horse- meat. Isolated cases have been reported from the con- Transmissible spongiform encephalopathies (TSEs) sumption of bear meat and ground beef in the USA. are fatal degenerative brain diseases which include The incidence of trichinosis can be controlled by BSE in cattle; scrapie in sheep; kuru, Creutzfeldt– avoiding feeding infected waste foods to pigs or by Jakob disease (CJD), and new variant CJD (vCJD) in fully cooking pig swill. Freezing pork products (−15°C humans. They are characterized by the appearance in for 20 days) or thorough cooking (78°C at the thermal the brain of vacuoles – clear holes that give the brain center) before human consumption will destroy tri- a sponge-like appearance – from which the condi- china larvae. tions derive their name. Cestodes Several theories have been proposed to explain the nature of the agents that cause TSE. Prusiner was Cestodes are tapeworms and the species of major awarded the Nobel Prize in 1997 for the prion theory, concern associated with consumption of fish is the which postulates that the agent is a proteinaceous fish tapeworm, Diphyllobothrium latum. Humans are infectious particle (PrP) that is capable of replication one of the definitive hosts, along with other fish- without the need of an agent-specific nucleic acid. eating mammals. Freshwater copepods and fish are The disease-associated prion (PrPSc) has been shown the intermediate hosts. The plerocercoid is present in to have a different helical shape to normal cellular the flesh of the fish and infects humans following the prion protein (PrPC) found on neuronal cells and consumption of raw or minimally processed fish. The some other cells, for example lymphoid cells. However, recorded epidemiology of D. latum shows it to be while it is widely acknowledged that PrPSc is very prevalent in many countries worldwide. The inci- closely associated with the causative agent, there is a dence is relatively high in Scandinavia and the Baltic reluctance by some to accept PrPSc as the sole agent region of Europe. Diphyllobothriasis in humans can responsible for transmission. Another hypothesis be prevented by cooking or freezing fish before con- suggests the agent is an unconventional virus, while a sumption. Infections with tapeworms are also associ- third suggests that it is a virion that has similar prop- ated with eating undercooked or raw pork and beef. erties to a virus but uses host proteins to coat its nucleic acid. Taenia saginata (the beef tapeworm) and Taenia solium (the pork tapeworm) are unique among para- Bovine spongiform encephalopathy sites in that they have no vascular, respiratory, or digestive systems. Humans are their definitive hosts BSE, sometimes referred to as “mad cow disease,” was and they rely solely on the human body for all of their first identified in the UK in 1986. The disease is fatal

Food Safety 339 Table 14.5 Food-borne protozoa Occurrence Transmission Definitive host Incubation Infective dose Pathogenesis 3–25 days Low (~10 cysts) Giardia intestinalis Food-borne, water- Humans, Chronic diarrhea, malabsorption, worldwide borne, person– domestic, and weight loss person wild animals Entamoeba 2–4 weeks Very low Amebiasis, abdominal pain, histolytica Food-borne, water- Humans (~1 cyst) fever, diarrhea, ulceration of worldwide borne, person– the colon (severe cases) person (food Humans, cats, Toxoplasma handlers) several 5–23 days ~1–30 cysts Mostly asymptomatic. In severe gondii mammals cases: hepatitis, pneumonia, worldwide Food-borne (raw or blindness, severe neurological inadequately disorders. cooked infected meat), water- Can also be transmitted borne, fecal–oral transplacentally resulting in a (infected cats) spontaneous abortion, a stillborn, or mental/physical Cyclospora Food-borne, Humans Several days Not known, retardation cayetanensis water-borne to weeks probably very worldwide Humans, low Often asymptomatic. Food-borne, water- domestic, and Difficult to Abdominal cramps, vomiting, Cryptosporidium borne, animal– wild animals define, in Very low (~1 parvum person, fecal–oral most cases cyst) weight loss, diarrhea worldwide 3–7 days, Often asymptomatic. occasionally Abdominal cramps, vomiting, longer weight loss, diarrhea to cattle within weeks to months of its onset. The (inherited) and associated with genetic mutations. incubation period is between 2 and 10 years. Affected Less than 1% are iatrogenic (i.e., accidentally trans- animals may display changes in temperament, such as mitted from person to person as a result of medical nervousness or aggression, abnormal posture, lack of or surgical procedures). Classically, sporadic CJD coordination, and difficulty in standing, decreased occurs in those over 65 years of age and presents as a milk production, or loss of body weight despite con- rapidly progressive dementia with myoclonus (shock- tinued appetite. Most cattle with BSE show a gradual like contractions of isolated muscles), usually fatal development of symptoms over a period of several within 6 months. Surveillance of CJD, a human neu- weeks or even months, although some can deteriorate rological disease, was reinstituted in the UK in 1990 very rapidly. While the original source of the agent to evaluate any changes in the pattern of the disease responsible for BSE remains unknown, currently that might be attributable to BSE. The overall inci- the most plausible explanation is that a novel TSE dence of CJD rose in the UK in the 1990s, although a appeared in the UK cattle population in the 1970s and portion of this increase was due to improved ascer- subsequently spread through contaminated meat and tainment of CJD in older people as a result of the bone meal fed to cattle. The International Office for reinstitution of surveillance. Epizootic Diseases (OIE) reports cases on its website (www.oie.int). New variant CJD, also referred to as variant CJD (vCJD), is a newly recognized disease in humans, Creutzfeldt–Jakob disease and new which was first diagnosed in the UK in the mid-1990s. variant CJD In contrast to the traditional forms of CJD, vCJD has affected younger patients (average age 29 years) and CJD is a fatal disease of humans, first described in the has a longer duration of illness (approximately 14 1920s and found worldwide. CJD is predominantly a months). Early in the illness, patients usually experi- sporadic disease, but about 14% of cases are familial ence behavioral changes, which most commonly take

340 Introduction to Human Nutrition the form of depression or, less often, a schizophrenia- regarding the incubation period between exposure to like disorder. Neurological signs such as unsteadiness, the infective agent and the emergence of symptoms. difficulty walking, and involuntary movements develop as the illness progresses and, by the time of 14.7 Chemicals affecting food safety death, patients become completely immobile and mute. Chemicals may be present in food owing to their natural occurrence in soil (e.g., cadmium, lead) or The link between BSE and vCJD from fungal contamination (e.g., aflatoxins, ochra- toxin), from algal contamination [e.g., amnesic shell- A geographical association exists whereby the major- fish poisoning (ASP), diarrhetic shellfish poisoning ity of BSE cases occurred in the UK and the majority (DSP), azaspiracid shellfish poisoning (AZP), para- of vCJD cases were also reported there. The emer- lytic shellfish poisoning (PSP)], from industrial or gence of BSE preceded vCJD, indicating a temporal other pollution [e.g., lead, mercury, polychlorinated association. Studies of stored human brain tissue biphenyls (PCBs), dioxins], from agricultural and vet- internationally have not identified the histopatho- erinary practices (e.g., pesticides, fertilizers, veteri- logical changes characteristic of vCJD before the nary drugs) or from food processing and packaging current BSE epidemic. Incubation period and patho- techniques [e.g. acrylamide, polycyclic aromatic logical lesion studies in mice and molecular typing hydrocarbons (PAHs), 3-monochloropropane-1,2- studies demonstrate that vCJD is similar to BSE but diol (3-MCPD), bisphenol A diglycidyl ether different from other TSEs. It is now widely accepted (BADGE)] (Box 14.1). that vCJD was transmitted to humans through the consumption of contaminated food. Toxicological assessment of these substances is largely carried out on an international basis by expert Estimates of future prevalence of vCJD vary widely groups such as the Joint Expert Committee on as too little is known about the disease, especially Box 14.1 Principal groups of chemicals affecting food safety Principal chemicals affecting food safety Additives Contaminants Residues Food additives Microbial toxins Pesticide residues Food flavorings Plant toxins Veterinary drug residues Process contaminants Processing aids Environmental contaminants Food contact materials Naturally occurring contaminants

Food Safety 341 Food Additives and Contaminants (JECFA) or Joint MTDI represents permissible human exposure as a Meeting on Pesticide Residues (JMPR), both jointly result of the natural occurrence of the substance in organized by the WHO and FAO. These expert groups food and drinking water. advise on acceptable or tolerable levels of intake of these substances. One of the most difficult issues in food safety is to advise on the potential risks to human health for Acceptable and tolerable levels of intake substances found in food which are both genotoxic (damaging DNA, the genetic material of cells) and The acceptable daily intake (ADI) level of a chemical carcinogenic (leading to cancer). For these substances, is the daily intake that, during a lifetime, would pose it is generally assumed that even a small dose can have no appreciable risk to the consumer, on the basis of an effect. JECFA addressed this issue in 1978 and all facts known at the time. It is expressed in mg/kg introduced the concept of an “irreducible level,” which of body weight (Box 14.2). it defined as “that concentration of a substance which cannot be eliminated from a food without involving The tolerable weekly intake (TWI) represents per- the discarding of that food altogether, severely com- missible human weekly exposure to those contami- promising the ultimate availability of major food sup- nants unavoidably associated with the consumption plies” (FAO/WHO, 1978). of otherwise wholesome and nutritious foods. The term tolerable signifies permissibility rather than Until now the risk assessors have advised to keep acceptability for the intake of contaminants that have the exposure to such substances at the lowest possible no necessary function in food, in contrast to those of level. This approach is known as the ALARA principle permitted pesticides or food additives. For cumulative (“as low as reasonably achievable”). A disadvantage of toxicants, such as lead, cadmium, and mercury, the this approach is that it cannot be used to compare tolerable intakes are expressed on a weekly basis risks posed by different substances. Furthermore, the to allow for daily variations in intake levels, the application of the ALARA principle does not take into real concern being long-term exposure to the account the effectiveness of a substance and the actual contaminant. (sometimes extremely low) level of occurrence in food. The maximum tolerable daily intake (MTDI) has been established for food contaminants that are not A different approach, “the margin of exposure” known to accumulate in the body, such as tin, arsenic, (MoE) approach, which can be used to assess the risks and styrene. The value assigned to the provisional to human health of exposure to a substance in the absence of a tolerable daily intake or similar guidance Box 14.2 Levels of intake of a chemical value, has recently been endorsed by the EFSA Scien- tific Committee (EFSA, 2005) and the WHO/FAO No observed effect Greatest concentration or amount of an Joint Expert Committee on Food Additives (WHO/ level (NOEL) agent, found by study or observation, FAO, 2005). The margin of exposure is defined as the ↓ that causes no detectable, usually reference point on the dose–response curve (usually adverse, alteration of morphology, based on animal experiments in the absence of human /Safety factor functional capacity, growth, data) divided by the estimated intake by humans. It ↓ development, or lifespan of the target enables the comparison of the risks posed by different /Safety factor genotoxic and carcinogenic substances. Differences in ↓ Uncertainty factor for extrapolating potency of the substances concerned and consump- Acceptable daily animal data to humans tion patterns in the population are taken into account when applying the MoE approach. intake (ADI) Human interspecies variation Setting the acceptable daily intake Daily intake that, during a lifetime, would pose no appreciable risk to the JECFA generally sets the ADI of a substance on the consumer, on the basis of all facts basis of the highest no-observed-effect level in animal known at the time. It is expressed in studies. In calculating the ADI, a “safety factor” is mg/kg of body weight applied to the no-observed-effect level to provide a conservative margin of safety on account of the inher-

342 Introduction to Human Nutrition ent uncertainties in extrapolating animal toxicity data or to regulate the growth of plants as crop protection to potential effects in humans and for variation within agents. They are classified into the groups shown in the human species. JECFA traditionally uses a safety Box 14.3. factor of 100 (10 × 10) in setting ADI values based on long-term animal studies. It is intended to provide an Most pesticides are toxic substances that are highly adequate margin of safety for the consumer by assum- selective, especially those developed since the early ing that the human being is 10 times more sensitive 1980s, and only have an effect on those pests or plants than the test animal and that the difference in sensi- to which they are applied. Unlike other environ- tivity within the human population is in a 10-fold mental contaminants, pesticides are applied under range. However, different safety factors apply depend- controlled conditions that should conform to “good ing on the substance and test species in question. agricultural practice” (GAP). This defines the effec- tive use of pesticides, up to the maximum allowable Maximum levels for food commodities dose, applied in a manner that ensures the smallest amount of residue in the foodstuff. These levels are calculated taking the above- mentioned levels into consideration. Depending on Pesticides can also be toxic to humans since certain the substance, different principles apply. Residues biochemical pathways are relatively conserved across such as pesticides and residues of veterinary drugs in species, as are some enzymes and hormones. In the foodstuffs are limited by setting a maximum residue context of food safety, exposure to pesticides is clas- limit (MRL). Additives are regulated by setting sified as acute or chronic. An acute intoxication maximum limits or by applying the “quantum satis” usually has an immediate effect on the body, whereas principle (the least amount required to exert the a chronic effect may reveal itself over the lifespan. The desired technological function). severity depends on the dose and the toxicity of the pesticide compound or breakdown product. Toxic For contaminants, maximum levels/limits are effects that have been identified include enzyme inhi- established for those foods that provide a significant bition, endocrine disruption, and carcinogenic action, contribution to the total dietary exposure. However, depending on the compound in question. as a general principle the levels in all foods should always be kept as low as reasonably achievable (the In Europe the control of pesticides is based on ALARA principle). Council Directive 91/414/EEC. Under this legislation, pesticides must be evaluated for safety based on dos- In Europe, additives, pesticides, veterinary residues, siers prepared by their manufacturers. If a pesticide is and a wide range of contaminants are regulated by accepted it is placed on a positive list with an MRL EU legislation in the form of directives or regulations assigned to it. that are transposed into national legislation by each member state. In the case of a limited number of highly toxic pesticides, for which the ADI is necessarily based on Pesticide residues acute toxicity rather than chronic toxicity, the level of exposure is considered in relation to the acute refer- Pesticides are chemicals or biological products used ence dose (ARfD). ARfD values are measures of the to control harmful or undesired organisms and plants, maximum level of intake at one meal, or consump- Box 14.3 Classification of pesticides Pesticides Insecticides Herbicides Fungicides Rodenticides Molluscides Plant growth regulators

Food Safety 343 tion over a day. This is the maximum intake level, hormone residues in foods of animal origin on human which is judged to result in no adverse toxicological metabolism. effect following such exposure. The ARfD value includes a safety factor to ensure that older people, Environmental and industrial contaminants infants and children, and those under stress due to illness are protected. These contaminants are of environmental origin or are by-products of industrial processes. Veterinary drug residues Polyhalogenated hydrocarbons (PHHs) are a cate- Veterinary drugs include antibacterial compounds, gory of environmental contaminants that includes hormones, and nonsteroidal anti-inflammatory prep- toxaphene, dioxins, and polychlorinated biphenyls arations. As animal husbandry practices have intensi- (PCBs). Certain polyhalogenated hydrocarbons are fied over the past few decades, antibacterial substances manufactured for use in plastics, paints, transformers, have been increasingly used as growth promoters and herbicides; although their use is now either to increase feed conversion efficiency, and for pro- banned or severely restricted. In most industrialized phylaxis and therapy to prevent outbreaks and treat nations the compounds have become ubiquitous in disease. Similarly, hormones are administered to the environment. Hence, contamination of the food increase growth rate and meat yield. Table 14.6 shows chain is inevitable and it has been estimated that in the main types of antibacterial and hormonal Western industrialized countries 90% of human compounds. exposure is through ingestion of contaminated foods such as fish and milk. Veterinary drugs are metabolized in the animal and are excreted in the urine and feces over time as Foods that are rich sources of fats and oils tend to the detoxification process continues. Hence, residue accumulate PHHs because the compounds are lipo- traces of drugs or their metabolites can be found philic and bioaccumulate in lipid-rich tissues and in major organs, muscles, and body fluids. In fluids. Oily fish from areas such as the Baltic Sea, general, antibacterial drugs are found in greatest where levels of PHHs in the water are high, may concentration in the kidney, lesser concentrations in contain elevated levels of these contaminants. Simi- the liver and lowest concentrations in the muscle larly, cows that graze on polluted pasture can accu- tissue, whereas hormones tend to concentrate in the mulate unacceptable concentrations of PHHs in their liver. milk. A recent incident in Belgium introduced PCBs and dioxins into the food chain via contaminated The excessive use of antibacterial compounds in animal feed resulting from the accidental incorpora- animal husbandry has raised concerns about the tion of industrial oil into the feed ration. The biologi- development of resistant bacteria and the effect that cal half-life of PHHs can range from a matter of this may have on the usefulness of antibiotics in months to 20 years in human adipose tissue. Hence, human medicine. There have also been concerns they are persistent and accumulate in the body. Expo- about the risk of allergic reactions in humans to anti- sure to PHHs can result in a variety of toxic effects bacterial residues in food of animal origin. The use of that can be carcinogenic, including dermal toxicity, hormones has raised issues surrounding the effects of immunotoxicity, reproductive effects, and endocrine disruption. Table 14.6 Main types of veterinary drugs Hormones Metals, metalloids, and their compounds have long Antibacterial compounds β-Agonists been associated with food poisoning, with lead and Resorcylic lactones mercury probably the best documented hazards. Aminoglycosides Steroids Metals are released into the environment as a result β-Lactams Stilbenes of natural geological action and also as a result of Fluoroquinolones Thyrostat man-made pollution from industrial processes. Macrolides Sulfonamides Metals have an affinity for biological tissue and Tetracyclines organic compounds, and hence they are often easily Quinolones absorbed into the body and can often accumulate in organs and fat deposits. Table 14.7 shows some of the main metals linked with food-borne toxicity.

344 Introduction to Human Nutrition Table 14.7 Metals in the food chain Acrylamide has been shown to be neurotoxic in humans. It has been shown to induce tumors in labo- Metal Main food sources ratory rats and has been classified as a probable human carcinogen, and as such several international Lead Shellfish, finfish, kidney, liver bodies have concluded that dietary exposure should Cadmium Shellfish, kidney, cereals, vegetables be as low as reasonably achievable. The most signifi- Mercury Finfish cant pathway of formation of acrylamide in foods has Arsenic Meat, vegetables, seafood been shown to arise from the reaction of reducing sugars with asparagines via the Maillard reaction at Lead toxicity has many symptoms, but the main temperatures above c. 120°C. Acrylamide has been issue relates to its effects on the nervous system of found in a wide range of heat-treated foods; it is children. Here, lead interferes with the transmission found in both foods processed by manufacturers and of nervous signals around the body. This can manifest foods that are cooked in the home. Acrylamide has itself in a reduced intelligence quotient (IQ) and been found to be most prevalent in fried potato prod- coordination problems. In adults, exposure to lead ucts (such as French fries and potato chips), cereals, can result in hypertension and other blood effects bakery wares, and coffee. such as anemia. Cadmium is most often accumulated from occupational exposure or smoking and is known PAHs are a group of over 100 different chemicals to affect the respiratory system. However, food expo- that are formed during certain technological pro- sure tends to be at a low level over longer periods. In cesses and are common environmental contaminants. this regard, cadmium bioaccumulates in the kidney They are formed during incomplete combustion of and can cause renal damage. Mercury and its com- coal and oil. They are also formed during barbecuing pounds also bioaccumulate in the body, where they or grilling meat. Human exposure usually results are most frequently associated with neural effects and from air pollution and from cigarette smoke. Foods renal damage. In particular, methylmercury is highly most likely to be contaminated by PAHs are grilled or toxic particularly to the nervous system, and the charred meats. PAHs are toxins that have been docu- developing brain is thought to be the most sensitive mented by the WHO as genotoxic, immunotoxic, and target organ for methylmercury toxicity. carcinogenic. Long-term exposure to foods contain- ing PAHs can lead to serious health risks. In a recent Arsenic is most often an occupational hazard, but Europe-wide incident, PAHs were found in pomace it can also be ingested with food and is responsible olive oil, which resulted in a major product recall. for acute and chronic poisoning. The toxicity of arsenic depends on its oxidation state and the type of 3-Monochloro-propane-1,2-diol (3-MCPD) is a complex that it forms with organic molecules in the member of a group of contaminants known as body. Chronic effects include gastroenteritis, nephri- chloropropanols, which includes known genotoxic tis, and liver damage. Arsenic is also considered to be animal carcinogens such as 1,3-dichloropropan-2-ol. a carcinogen. Other metals are also known contami- 3-MCPD is a by-product in soy sauce and in hydro- nants and their toxic effects are diverse. Although this lyzed vegetable protein produced through acid hydro- is not an exhaustive list, these metals include alumi- lysis. It can also be present as a contaminant in some num, copper, tin, zinc, and chromium. food additives, and in epichlorhydrin/amine copoly- mers, used as flocculants or coagulant aids in water Process contaminants treatment, and may be present in drinking water (opinion of the European Scientific Committee on These types of contaminant occur during the process- Food, adopted on 30 May 2001). ing and production of foods, and include acrylamide, PAHs, chloropropanols, and nitrosamines. Microbial toxins Acrylamide is a reactive unsaturated amide that has Food poisoning can occur as a result of the ingestion found several industrial uses. In 2002, it was discov- of food containing preformed toxins that originate ered to occur in a variety of fried and baked foods, from bacterial growth, fungal growth, or algal growth. in particular carbohydrate-rich foods that had been In the case of bacteria the toxin is absorbed into the subjected to high-temperature cooking/processing. bloodstream via the intestine and therefore illness

Food Safety 345 results from intoxication rather than infection. In the to suppression of their immune systems and greater case of fungi, several species are involved in the pro- susceptibility to disease. duction of toxic substances during growth on food- stuffs. These toxins are known as mycotoxins. Algal The principal fungi that are associated with myco- toxins are usually associated with seafood, most toxin production are the genera Aspergillus, Penicil- notably molluscan shellfish. lium, and Fusarium. Aspergillus and Penicillium are sometimes referred to as storage fungi as they can grow Bacterial toxins at low water activity levels and are associated with the post-harvest spoilage of stored food commodities such Three bacteria are most commonly associated as cereals, nuts, and spices. Fusarium species are plant with preformed toxin production: Clostridium botu- pathogens and can infect plants in the field and produce linum, Staphylococcus aureus and Bacillus cereus (see mycotoxins preharvest. Table 14.8 provides an over- Table 14.1). view of the most important mycotoxins. Fungal toxins (mycotoxins) Seafood toxins Mycotoxins are secondary metabolites of molds that Fish and fishery products are nutritious foods and are can induce acute and chronic symptoms, such as desirable components of a healthy diet. Food-borne carcinogenic, mutagenic, and estrogenic effects in illnesses resulting from the consumption of seafood humans and animals. Acute toxicity due to mycotox- are associated with both finfish and molluscan shell- ins is associated with liver and kidney damage. fish. The major risk of acute illness is associated with Chronic toxicity resulting from the exposure of low the consumption of raw shellfish, particularly bivalve levels of mycotoxins in the human diet is a major food molluscs. The consumption of these toxic shellfish by safety concern. In nonindustrialized countries myco- humans can cause illness, with symptoms ranging toxins have been reported to be responsible for from mild diarrhea and vomiting to memory loss, increased morbidity and mortality in children owing paralysis, and death. Toxins associated with phyto- Table 14.8 Mycotoxins in the food supply Mycotoxin Producing fungi Main foods affected Toxicity Aflatoxins Aspergillus flavus and A. parasiticus Nuts, cereals, dried fruit, herbs Carcinogenic, hepatotoxic Ochratoxin A and spices, milk (aflatoxin M1) Nephrotoxic, immunotoxic Aspergillus ochraceus, Penicillium Patulin verrucosum, and other Aspergillus Coffee, dried fruit, cereals, beans, Cytotoxic and Penicillium spp. pulses, wine, beer, grape juice; Dermotoxic, enterotoxic, hemotoxic, Trichothecenes kidney, liver and blood from (nivalenol, Aspergillus clavatus, also several animals fed with contaminated immunotoxic deoxynivalenol, species of Penicillium, Aspergillus, feed T2-toxin, etc.) and Byssochlamys Fruits and grains, predominantly Fumonisins Fusarium spp. apples and apple products Sterigmatocystin Citrinin Wheat, maize, barley, oats, rye, Zearalenone malt, beer, bread Moniliformin Fusarium spp. Cereals, mainly corn Carcinogenic, cytotoxic, hepatotoxic Aspergillus versicolor, A. nidulans, Cereals, green coffee, herbs and Hepatotoxic and nephrotoxic, and other Aspergillus spp. spices, raw meat products carcinogenic Penicillium spp., Aspergillus spp. Cereals Nephrotoxic Fusarium graminearum Maize, barley, oats, wheat, rice, Estrogenic effects, feed refusal, Fusarium spp. sorghum, bread vomiting Cereals, maize Nephrotoxic, causes necrosis of the heart muscle

346 Introduction to Human Nutrition plankton are known as phycotoxins. These toxins Adequate cooking of legume seeds such as kidney have been responsible for incidents of wide-scale beans and disposal of the cooking water will remove death of sea-life and are increasingly responsible for the natural toxins present in these food products. human intoxication. Antinutritional factors are those components of Various seafood poisoning syndromes are associ- plants that interfere with metabolic processes and can ated with toxic marine algae and these include para- lead to deficiencies of key nutrients in the diet. These lytic shellfish poisoning (PSP), amnesic shellfish are generally classified as enzyme inhibitors and poisoning (ASP), diarrhetic shellfish poisoning (DSP), mineral binding agents. Enzyme inhibitors are poly- neurotoxic shellfish poisoning, and azaspiracid shell- peptides and proteins that inhibit the activities of fish poisoning (AZP). There are also different types digestive enzymes, and most are thermolabile and are of food poisoning associated with finfish and these reduced by cooking. For example, trypsin inhibitors include ciguatera poisoning, scombroid or histamine may cause poor protein digestion and a shortage of poisoning, and puffer fish poisoning. Consumption sulfur-containing amino acids in the diet. Lectins are of raw molluscan shellfish poses well-known risks of proteins that occur in beans that alter the absorption food poisoning, but intoxication from finfish is not of nutrients in the intestinal wall. Cooking beans so well known. Most of the algal toxins associated will inactivate lectins. Tannins (polyphenols) occur with seafood poisoning are heat stable and are not in cereals, specifically in the seed coat. These form inactivated by cooking. It is also not possible visually complexes with proteins and inhibition of digestive to distinguish toxic from nontoxic fish. Many coun- enzymes. Phytate is a natural component in plants tries rely on biotoxin monitoring programs to protect and on digestion forms insoluble complexes with public health and close harvesting areas when toxin metal ions in the body. The result is reduced bioavail- algal blooms or toxic shellfish are detected. In nonin- ability of essential minerals such as iron. In addition, dustrialized countries, particularly in rural areas, a range of natural plant toxins can cause allergic reac- monitoring for harmful algal blooms does not rou- tions in humans, but there is a general lack of knowl- tinely occur and deaths due to red-tide toxins com- edge about their properties and modes of action. monly occur. Table 14.9 provides an overview of the most important types of fish poisoning. Food additives Naturally occurring plant toxins Food additives are added to foods for a specific tech- nological purpose during manufacture or storage and Certain plants contain naturally occurring com- become an integral part of that foodstuff. Additives pounds that are toxic to humans or that reduce the can be natural or synthetic and are usually catego- bioavailability of nutrients in foods. Examples of rized by their function (Table 14.11). For example, naturally occurring toxins are listed in Table 14.10. preservatives prevent the growth of bacteria, gelling Some species of mushroom also contain toxic com- agents maintain the structure of some foods during pounds, for instance agaritine. Some cereal-based storage, and emulsifiers maintain the stability of fat diets have restricted bioavailability of nutrients as a structures. Without additives it would not be possible result of the presence of antinutritional factors such to manufacture many of the foods available today, as phytate and tannins or polyphenols. especially convenience foods and low-fat foods. Food processing methods have evolved that reduce Safety considerations involving additives have cen- human exposure to both natural toxins and antinu- tered on allergic reactions and food intolerances.Addi- tritional compounds. For instance, cassava is a staple tives have also been blamed for inducing hyperactivity food of over 500 million people worldwide. Certain in children. Studies have been conducted into allergies bitter varieties of cassava contain high levels of lin- and they often find that the actual prevalence rate is amarin, a cyanogenic glycoside. The consumption of much lower than the perceived prevalence rate. these varieties has been associated with health defects such as goiter and paralysis of the legs. Traditional At the international level, additives are controlled processing of cassava in Africa that involves grating, by means of safety evaluation and the development soaking roots in water, and lactic acid fermentation of a positive list. To ensure transparency and choice, completely removes the cyanide. all additives that are used in prepackaged food should be labeled with their function and their name or

Table 14.9 Types of fish poisoning Poisoning Implicated foods Associated Sy toxin Ne Paralytic shellfish Mussels, oysters, clams or scallops that have Saxitoxins Vo poisoning fed on toxigenic dinoflagellates (Gonyaulax Ab spp.) Domoic acid Amnesic shellfish Na poisoning Mussels and clams that have recently fed on a Okadaic acid Na marine diatom Nitzchia pungens, viscera of and Ga Diarrhetic shellfish crabs and anchovies associated poisoning toxins Toxic mussels, clams, and scallops that have Neurotoxic shellfish fed on marine dinoflagellates (Dinophysis Brevitoxins poisoning spp.) Azaspiracid Azaspiracid shellfish Shellfish that have fed on the dinoflagellate poisoning Gymnodinidum breve Ciguatera Ciguatera fish Mussels, oysters, clams, scallops, and razor poisoning fish Flesh of toxic reef fish from tropical areas feeding on dinoflagellates (Gambierdiscus toxicus) and their toxins. Common species are amberjack, barracuda, moray eel, groupers, trevally, Spanish mackerel, and snapper Scombroid or Consumption of scombroid and scombroid- Scombroid or In histamine like marine fish species that have not been histamine. Sy poisoning chilled immediately af ter capture. Commonly involved are members of the Tetrodotoxin Puffer fish Scombridae family, e.g., tuna and mackerel, poisoning and a few nonscombrid relatives, e.g., bluefish, dolphin fish, and amberjack Consumption of fish species belonging to the Tetraodontidea family, particularly those species caught in waters of the Indo-Pacific Ocean regions

ymptoms Occurrence Worldwide eurotoxic; symptoms include numbness, tingling and burning of the lips, staggering, drowsiness, and in USA, Canada, and Europe severe cases respiratory paralysis Europe, Japan, Chile, New omiting, cramps, diarrhea, disorientation, and difficulty in Zealand, and Canada breathing bdominal pain, nausea, vomiting, and severe diarrhea ausea, diarrhea, tingling and burning of the lips, tongue, Florida coast and Gulf of Mexico Food Safety 347 and throat Ireland, suspected cases in ausea, vomiting, severe diarrhea, and stomach cramps Norway, the Netherlands, Scotland, and Japan astrointestinal (diarrhea, vomiting, abdominal pain, Tropical reef waters, particularly nausea); neurological (paresthesia of the extremities, in the island states of the circumoral paresthesia, temperature reversal, ataxia, South Pacific arthralgia, malign headache, severe pruritus, vertigo, and stiffness, convulsions, delirium, hallucinations, Worldwide photophobia, transient blindness, salivation, perspiration, watery eyes, metallic taste in mouth, Most frequent in Japan, where blurred vision, hiccups, exacerbation of acne, dysuria); puffer fish (called fugu in cardiovascular (dyspnea, bradycardia, hypotension, Japan) are eaten as a tachycardia) delicacy, Indo-Pacific Ocean region nitial symptoms are that of an allergic response with facial flushing and sweating, burning–peppery taste sensations around the mouth and throat, dizziness, nausea, and headache. A facial rash can develop as well as mild diarrhea and abdominal cramps. Severe cases may blur vision and cause respiratory stress and swelling of the tongue. Symptoms usually last for approximately 4–6 h and rarely exceed 1–2 days ymptoms of puffer fish poisoning are similar to paralytic shellfish poisoning as the actions of both toxins are similar. Mild poisoning results in tingling and numbness of the lips, tongue, and fingers, and in severe cases death by asphyxiation due to respiratory paralysis

348 Introduction to Human Nutrition Table 14.10 Naturally occurring plant toxins be controlled through the development and imple- mentation of targeted food safety control programs. Compound Food species Common name This can be achieved either through legislation, or the use of standards or codes of practice. At the interna- Glycosides: Manihot escaleatum Cassava tional level, the WHO and the FAO have worked since Linamarin Sorghum spp. Sorghum the 1960s on developing food standards that aim to Dhurrin Prunus spp. Cherries protect the health of consumers and facilitate inter- Prunasin national trade of foods and animal feeding stuffs. Solanium tuberosiem Potatoes This work is carried out by the Codex Alimentarius Glycoalkaloids: Commission (CAC), an intergovernmental body Solanin Symphytum spp. Comfrey managed by the FAO and WHO. Food safety stan- Senccio jacobata Ragwort dards developed by the CAC serve as the baseline Pyrrolizidine alkaloids: for harmonization of global food standards, codes Acetyllycopsaimine Brassica spp. Cabbage of practice, guidelines, and recommendations. Senecionine Broccoli Harmonization of standards and recognition that dif- Brussels ferent national food safety controls are equivalent are Glucosinolates: sprouts enshrined in the international agreements of the Sinigrin World Trade Organization (WTO). Table 14.11 Categories of food additives according to function The purpose of food safety legislation is to protect consumers’ health and interests by providing controls Acid Flour treatment agent throughout the food chain. A recent overhaul of EU Acidity regulatora Gelling agent food safety legislation now places the primary respon- Anticaking agent Glazing agentc sibility for food safety with the food business opera- Antifoaming agent Humectant tor. It also recognizes that food safety must start at Antioxidant Modified starch primary production (i.e., the farmer) and places Bulking agent Preservative increased importance on the safety of animal feed. Color Propellant gas and This concept of food safety control from “farm-to- fork” or “gate-to-plate” has been endorsed interna- Emulsifier packaging gas tionally, but implemented differently in different Emulsifying salt countries. Enzymeb Raising agent Firming agent Sequestrantd The traditional “inspection and detection” aspects Flavoring Stabilizere of food safety control are now being replaced with Flavor enhancer Sweetener strategies for prevention of hazards occurring in the Thickener first place. In many countries, food businesses are now legally obliged to adopt the principles of HACCP a These can act as two-way acidity regulators. (hazard analysis and critical control point) in order b Only those used as additives. to predict what biological, chemical or physical c These substances include lubricants intended for the final consumer. hazards are likely to occur in their process, so that d Inclusion of these terms in this list is without prejudice to any future they can implement control measures to prevent them happening. decision or mention thereof in the labeling of foodstuffs. e This category also comprises foam stabilizers. 14.9 Perspectives on the future Source: European Union Directive 89/107/EEC, http://eur-lex.europa. As our society changes, so do the bacteria involved in food-borne disease. Changes in food production eu/. © European Communities. systems and the globalization of the food supply, as well as changes in the food we are eating, and where approval number (E number). However, there are this food is prepared, expose us to an ever-changing some exemptions specifically applying to additives spectrum of contamination. The global nature of our that are in a foodstuff as a result of carry-over from an ingredient. 14.8 Food safety control programs Each nation has a responsibility to ensure that its citi- zens enjoy safe and wholesome food. Governments aim to identify major food safety issues that can then

Food Safety 349 food supply poses greater risks to consumer health References from the mass production and distribution of foods and increased risk for food contamination. New food Abdussalam M, Käferstein FK, Mott K. Food safety measures for development has led to changing vectors for the the control of food borne trematode infections. Food Control spread of disease. Inappropriate use of antibiotics 1995; 6: 71–79. in animal husbandry can lead to the emergence of antibiotic-resistant food-borne pathogens such as Cadbury Schweppes. Press Release 2007. Available at: http://www. S. typhimurium DT 104. cadbury.com/media/press/Pages/2006fullyearresults.aspx Food safety and nutrition are inextricably linked CDC. Surveillance for Foodborne Disease Outbreaks – United because food-borne infections are one of the most States, 1993–1997. Morbidity and Mortality Weekly Report 2000; important underlying factors of malnutrition, espe- 49: (SS01)1–51. cially in poorer countries. Repeated episodes of food- borne infections can, over a period of time, lead to Dewaal CS, Hicks G, Barlow K, Aldterton L, Vegosen L. Foods malnutrition, with serious health consequences. A associated with food-borne illness outbreaks from 1990 through safe food supply is essential for proper nutrition, basic 2003. Food Protection Trends 2006; 26: 466–473. health and well-being. Doyle MP, Beuchat LR, Montville TJ, eds. Food microbiology: Maintaining a safe food supply is not difficult; fundamentals and frontiers, 2nd ed. American Society for however, it requires attention to detail at all stages of Microbiology, Washington DC, 2001. the food chain from agricultural inputs through farms, processing, the distribution network to retail- EFSA. Opinion of the Scientific Committee on a request from EFSA ers and catering outlets to consumers. There can be related to a harmonised approach for risk assessment of sub- no gaps in the continuum from farm to fork if con- stances which are both genotoxic and carcinogenic. EFSA Journal sumer protection is to be optimum. To ensure con- 2005; 282: 1–31. sumer protection, food standards have to be based on sound science and the principles of risk analysis. At EFSA. The community summary report on trends and sources of the national level, food safety controls must be well zoonoses, zoonotic agents, antimicrobial resistance and food- coordinated and based on proportionate food legisla- borne outbreaks in the European Union in 2006. Available at: tion. The food industry must also recognize its http://www.efsa.europa.eu/cs/BlobServer/DocumentSet/Zoon_ primary responsibility for producing safe food and report_2006_en,0.pdf?ssbinary=true for ensuring that foods placed on the market meet the highest standards of food safety and hygiene. A mul- European Commission. Opinion of the Scientific Committee on tisectoral effort on the part of regulatory authorities, Food on 3-monochloro-propane-1,2-diol (3-MCPD) updating food industries. and consumers alike is required to the SCF opinion of 1994 adopted on 30 May 2001. Available at: prevent food-borne diseases. http://ec.europa.eu/food/fs/sc/scf/out91_en.pdf Acknowledgment FAO/WHO. Evaluation of certain food additives and contaminants. 22nd Report of the Joint FAO/WHO Expert Committee on Food This chapter has been revised and updated by Alan Additives. WHO Technical Report Series No. 631. WHO, Geneva, Reilly, Christina Tlustos, Judith O’Connor, and Lisa 1978: 14–15. O’Connor based on the original chapter by Alan Reilly, Christina Tlustos, Wayne Anderson, Lisa Frenzen PD. Deaths due to unknown foodborne agents. Emerging O’Connor, Barbara Foley, and Patrick Wall. Infectious Diseases 2004; 10: 1536–1543. Frenzen PD, Drake A, Angulo FJ, the Emerging Infections Program Foodnet Working Group. Economic cost of illness due to Escherichia coli O157 infections in the United States. Journal of Food Protection 2005; 68: 2623–2630. Käferstein, FK. Actions to reverse the upward curve of foodborne illness. Food Control 2003; 14: 101–109. McCabe-Sellers BJ, Beattie SE. Food safety: emerging trends in foodborne illness surveillance and prevention. Journal of the American Dietetic Association 2004; 104: 1708–1717. Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, Griffin PM, Tauxe RV. Food-related illness and death in the United Sates. Emerging Infectious Diseases 1999; 5: 607– 625. Smith JL. Foodborne infections during pregnancy. Journal of Food Protection 1999; 62: 818–829. WHO. Food safety and foodborne illness. Fact sheet No. 237. Available at: http://www.who.int/mediacentre/factsheets/ fs237/en/ WHO/FAO. Joint FAO/WHO expert committee on food additives sixty-fourth meeting, Rome, 8-–17 February 2005. Available at: ftp://ftp.fao.org/es/esn/jecfa/jecfa64_call.pdf

15 Food and Nutrition-Related Diseases: The Global Challenge Hester H Vorster and Michael J Gibney Key messages undernutrition and related deficiency and infectious diseases (including human immunodeficiency virus/acquired immunodefi- • This chapter deals with the current situation, trends and types ciency syndrome HIV/AIDS), and the emergence of NCDs as of nutrition-related diseases in developed and developing a result of the nutrition transition. It explains the vicious cycle countries. of poverty and undernutrition and how this is related to under- development and increased risk of NCDs in the developing • It shows that in developed countries excessive intakes of macro- world. nutrients (overnutrition) and suboptimal intakes of micronutrients • Current global challenges for food and nutrition interventions on (hidden hunger), mainly because of low fruit and vegetable con- different levels are highlighted. sumption, lead to obesity and related noncommunicable diseases (NCDs). • The chapter also shows that developing countries are suffering from a double burden of disease because of the persistence of 15.1 Introduction and promotion have responded to this preference by making high energy-dense foods available at increas- The relationship between nutrition and health was ingly affordable prices. This has led to changes in food summarized in Figure 1.2, illustrating that the nutri- consumption patterns which unfortunately coincided tional quality and quantity of foods eaten, and there- with more sedentary, less active lifestyles. The resul- fore nutritional status, are major modifiable factors tant overnutrition of especially macronutrients is the in promoting health and well-being, in preventing major cause of obesity and also, together with obesity, disease, and in treating some diseases. It is now a risk factor for many of the noncommunicable accepted that our nutritional status influences disease (NCDs) such as type 2 diabetes, coronary our health and risk of both infectious and non- heart disease, stroke, hypertension, dental disease, communicable diseases. osteoporosis, and some forms of cancer. But it is also accepted that billions of people in both These changes from traditional low-energy dense, developed and developing countries suffer from one high-fiber diets to the dietary pattern described above or more forms of malnutrition, contributing to the are collectively known as the nutrition transition (NT). global burden of disease. Mankind has an inherent The NT has proceeded gradually over centuries in the preference for palatable, sugary, salty, fatty and smooth developed world and accelerated during the industrial (finely textured, refined) foods. These foods are revolution with a resultant gradual and then acceler- mostly energy-dense and low in micronutrients. Food ated emergence of the NCDs. However, globalization production, processing, manufacturing, marketing characterized by urbanization, acculturation, global © 2009 HH Vorster and MJ Gibney.

Food and Nutrition-Related Diseases 351 trade, and information exchange has led to a very rapid disease, stroke, diabetes mellitus (type 2), osteoporo- NT in developing countries. The consequence is that, sis, liver cirrhosis, dental caries, and nutrition-induced different from developed countries, obesity and the cancers of the breast, colon, and stomach. They NCDs emerged before the problems of undernutrition develop over time in genetically susceptible individu- and specific nutritional deficiencies have been solved. als because of exposure to interrelated societal, Developing countries now suffer from a double burden behavioral, and biological risk factors. Together with of nutrition-related diseases because of the coexis- tobacco use, alcohol abuse, and physical inactivity, tence of under- and overnutrition. This dual burden is an unhealthy or inappropriate diet is an important further exacerbated by the HIV/AIDS and TB pan- modifiable risk factor for NCDs. Diet, therefore, plays demics in these countries. a major role in prevention and treatment of NCDs. NCDs are sometimes called “chronic diseases,” but The purpose of this chapter is to describe the major some infectious diseases such as HIV/AIDS and nutrition-related diseases in the developed and devel- tuberculosis are also chronic. They have also been oping world, to show the interrelationships between called “diseases of affluence,” which is a misnomer the causes and consequences of under- and over- because in developed, affluent countries, they are nutrition, and to identify the global challenges in more common in lower socioeconomic groups. Some addressing the heavy burden of malnutrition that scientists have a problem with the term “noncom- contribute to underdevelopment, disability, and pre- municable” because lifestyles, including diets, are mature death. transferable between populations. The term “non- communicable” should therefore be seen as no 15.2 Nutrition-related diseases in transfer of an infectious agent from one organism to developed countries another.Because of its first emergence in“Westernized” societies and associations with Western lifestyles, it is The current situation often called “Western” diseases, also a misnomer. It is becoming more prevalent in developing countries in Economic development, education, food security, and other parts of the world. Another misconception is access to health care and immunization programs that it is a group of diseases affecting only older in developed countries have resulted in dramatic people. The risk factors for NCDs accumulate decreases in undernutrition-related diseases. Un- throughout the life course – from infancy to adult- fortunately, many of these factors have also led to hood, and manifest after decades of exposure. The unhealthy behaviors, inappropriate diets, and lack of increase in childhood obesity is especially of concern physical activity, which has exacerbated the develop- because it has long-term implications for NCDs in the ment of chronic diseases, also known as noncommu- developed world. nicable diseases (NCDs). These NCDs are now the main contributors to the health burden in developed Risk factors for NCDs countries (these are countries with established market economies). Table 15.1 lists the risk factors for NCDs. The factors are interrelated and form a chain of events starting In 2002, 28.2 million global deaths (58.6%) were with societal factors such as socioeconomic status and from NCDs. In the same year the predicted mortality environments that influence behavior, leading to the for 2020 was 49.6 million (72.6% of all deaths). This development of biological risk factors that cause the is an increase from 448 to 548 deaths per 100,000, NCDs. The biological risk factors often cluster despite an overall downward trend in mortality rates. together. For example, obesity (abnormal body com- Although the burden will fall increasingly on develop- position) is associated with insulin resistance, hyper- ing countries (see 15.3) NCDs remain the major cause lipidemia, and hypertension, which all contribute to of death in developed countries. the development of both cardiovascular disease and diabetes. Cardiovascular disease is furthermore one of Definition, terminology and characteristics the complications of untreated diabetes. The mecha- nisms through which these risk factors contribute to The NCDs that are related to diet and nutrient intakes the development of NCDs are discussed in detail in are obesity, hypertension, atherosclerosis, ischemic heart disease, myocardial infarction, cerebrovascular

352 Introduction to Human Nutrition Table 15.1 Risk factors for nutition-related noncommunicable diseases (NCDS) Societal Behavioral Biological NCDs Socioeconomic status Smoking Tobacco addiction Lung disease Cultural habits Alcohol abuse Alcohol addiction Cardiovascular disease Environmental factors Lack of physical activity Dyslipidemia Inappropriate diets: Hyperlipidemia Atherosclerosis inadequate Insulin resistance Cerebrovascular disease Hypertension Stroke fiber Obesity (body composition) Ischemic heart disease micronutrients Myocardial infarction excess Diabetes total fat Osteoporosis saturated fat Dental caries trans fat Cirrhosis cholesterol Diet-induced cancers salt (NaCl) energy appropriate chapters and sections of this series of Box 15.1 The WHO population nutrient intake goals for textbooks. prevention of death and disability from NCDsa The role of nutrition Dietary factor Recommended goal (food or nutrient) (range) The evidence that diets and specific nutrient deficien- cies and excesses influence the development of NCDs Total fat 15–30% of total energy and may therefore be used in prevention and treatment Saturated fatty acids <10% of total energy is solid. It comes from extensive research which collec- Polyunsaturated fatty acids (PUFAs) 6–10% of total energy tively gave convincing evidence of the relationships 5–8% of total energy between nutrition and NCDs: first, from ecological n-6 PUFAs 1–2% of total energy studies which compared different populations, the n-3 PUFAs <1% of total energy effects of migration of populations, food availability Trans fatty acids By differenceb during economic development, and differences in Monounsaturated fatty acids (MUFAs) 55–75% of total energyc dietary and nutrient intakes. Second, numerous epide- Total carbohydrate <10% of total energy miological studies have established the associations Free sugarsd 10–15% of total energy between diet and biological risk factors of NCDs. Third, Protein <300 mg per day interventions with specific nutrients and foods in Cholesterol <5 g per day placebo-controlled trials using both healthy and dis- Sodium chloride (sodium) eased subjects confirmed the relationships seen in epi- (<2 g per day) demiological studies. And last, molecular and genetic Fruits and vegetables ≥400 g per day research has elucidated many mechanisms through Total dietary fiber >25 g per day which diet and nutrients affect genetic mutation and Non-starch polysaccharides >20 g per day expression, adding to our knowledge of how nutrition influences NCD development. This body of knowledge a WHO Technical Support Series No. 916. has led to several sets of international dietary recom- b MUFAs are calculated as total fat minus saturated plus polyun- mendations and guidelines to reduce the burden of saturated plus trans fatty acids). nutrition-related NCDs. An example of one such set of c Energy from carbohydrate is the percentage energy available after guidelines from the World Health Organization (WHO) taking into account that consumed as fat and protein. is shown in Box 15.1. These generic recommendations d Free sugars refers to all monosaccharides and disaccharides added could be used as the basis for the development of to foods by the manufacturer, cook, or consumer, plus sugars natu- country-specific strategies and food-based guidelines rally present in honey, syrups, and fruit juices. It does not include for dietary prevention of NCDs. sugars present in milk, fruit and vegetables.

Food and Nutrition-Related Diseases 353 Prevention of NCDs in developed countries and have difficulties with body image and mobility. Overweight and obese children often become over- The complex chain of events where behavioral and weight or obese adults and carry the long-term risk lifestyle factors influence the development of the bio- of premature morbidity and mortality from NCDs. logical risk factors for NCDs, emphasizes the need for Children in the developed world are exposed to a food a multisectorial approach in which all factors in the environment in which high energy-dense and micro- chain are targeted throughout the life course. In addi- nutrient-poor foods, beverages, and snacks are avail- tion to the medical treatment of some biological risk able, affordable, and aggressively marketed. This factors (such as pharmacological treatment of hyper- illustrates that to address the problem of childhood cholesterolemia) and of the NCD itself (such as blood obesity, active and responsible partnerships and glucose control in diabetes) there is convincing common agendas should be formed between all evidence that primary prevention is possible, cost- stakeholders (for example between governments, effective, affordable, and sustainable. In the developed NGOs and the food industry). There are indications world, early screening and diagnosis, and access to that dialogue with the food industry is not sufficient, health care make primary prevention more feasible and that many countries are now considering or than in many developing countries. However, over- already implementing legislation to create a more coming the barriers to increase physical activity and healthy food environment for children. The problems changing dietary behavior towards more prudent, of childhood overweight and obesity and consequent low-fat, high-fiber diets may be more difficult. The increases in NCDs are not only seen in developed strategies and programs to prevent NCDs would be countries. They are emerging in developing countries similar in developed and developing countries, and in some the total number of children affected although the context and specific focus of different exceeds those in developed countries. Timely inter- interventions may vary. Because the future burden of ventions are needed to prevent the escalation experi- NCDs will be determined by the accumulation of enced in developed countries. risks over a lifetime, the life course approach is rec- ommended. This will include optimizing the nutri- 15.3 Nutrition-related diseases in tional status of pregnant women (see Box 15.3), developing countries breastfeeding of infants, ensuring optimal nutrition status and growth of children, preventing childhood The poverty–malnutrition cycle obesity and promoting “prudent” diets for adoles- cents, adults, and older people. Addressing childhood Malnutrition in developing countries affects individ- obesity in developed countries is one of the biggest uals throughout the life course: from birth to infancy nutritional challenges these countries is facing today. and childhood, through adolescence into adulthood, Increases in the prevalence of childhood obesity have and into old age. Malnutrition affects, therefore, criti- been documented for most developed countries. cal periods of growth and mental development, In the USA, the National Health and Nutrition maturation, active reproductive as well as economical Examination Surveys (NHANES) showed substantial productive phases. increases over the last two decades in overweight and obese children aged 2–19 years. More than 15% of The health of populations in developing countries American children are currently considered obese. is largely determined by their environment. “Environ- The International Obesity Task Force estimates that mental” factors include social and economic con- at least 22 million of the world’s children under 5 ditions depending on and influencing availability years of age are overweight or obese. Overweight and and distribution of resources, agricultural and food obesity have dire consequences in children. These systems, availability and access to nutritious food and children already display many of the other biological safe drinking water, implementation of immuniza- risk factors of NCDs. There are also immediate health tion programs, exposure to unhygienic surroundings consequences such as risks to develop gallstones, hep- and toxins, women’s status and education, as well as atitis, sleep apnea, and others. Moreover, these chil- the “political” milieu including dictatorships, conflict, dren have a lack of self-esteem, are often stigmatized and war, which often determine the availability of health services. There is a close, interrelated

354 Introduction to Human Nutrition association between undernutrition and poverty in disease. In 2000, more than 150 million preschool developing countries. children in the developing world were underweight, while approximately 200 million were stunted. Figure 15.1 illustrates this relationship, also showing some of the mechanisms responsible for perpetuating Figure 15.1 also shows that these physically and the relationship over generations. mentally underdeveloped children eventually develop into adults with “decreased human capital” and Approximately 243 million adults in developing decreased competence. These adults are often not able countries are severely undernourished, with a body to create enabling environments for themselves or mass index less than 17 kg/m2. This means that high their children to escape poverty and undernutrition proportions of especially Asian and African preg- in the next generation. But moreover, these “under- nant women are undernourished. Intrauterine (fetal) developed” adults are at increased risk of obesity and growth retardation is common in these women, other NCDs because of early programming (possibly leading to low birthweight babies (weight at full term through epigenetic or DNA methylation changes) in less than 2500 g). Almost a quarter of newborns in the the undernourished fetus. It is especially when these developing world (30 million of the 126 million babies adults are exposed to low micronutrient quality and born each year) have low birth weights compared with high energy-dense diets that they rapidly become only 2% in the developed world. These babies, espe- overweight and obese. This phenomenon explains to cially when exposed to inappropriate breastfeeding a certain extent the coexistence of under- and over- and weaning practices, leading to further nutritional nutrition in the same household with undernour- insults, have growth impairment and mental under- ished, wasted, and stunted children being cared for by development. In addition, because of undernutrition, an overweight or obese mother or care-giver. their immune systems are compromised. The result is stunted children that cannot benefit optimally from Obesity and noncommunicable diseases in education and with an increased risk of infectious developing countries UNDERNUTRITION Obesity and other NCDs are increasingly becoming major public health problems in the developing (undernourished pregnant mothers; world. The WHO estimates that almost 80% of all Fetal growth restriction) deaths worldwide that are attributable to NCDs are already occurring in developing countries. A disturb- POVERTY Low birthweight babies ing observation is that they often occur at younger Undernourished infants ages than in the developed world. Obesity and other NCDs have similar biological risk factors in devel- Lack of care oped and developing countries (and will not be dis- Unhygienic environments cussed in detail here). However, the context in which they develop may differ, being linked with fetal and Food insecurity infant undernutrition. Also, underdevelopment and a lack of resources in developing countries limit the Adults with decreased •Growth impairment availability of diagnostic and therapeutic care of human capital and competence (underweight; stunting) people suffering from NCDs, leading to increased morbidity and mortality. •Mental underdevelopment The other two groups of nutrition-related diseases •Compromised immune system in developing countries are nutrient deficiency dis- eases and infectious diseases, which will now be briefly Increased risk of Inappropriate discussed. obesity and other NCDs breastfeeding and weaning Major nutrient deficiency diseases in Increased risk of infectious developing countries disease Micronutrient deficiencies It is estimated that nearly 30% of humanity suffer (Fe, Zn, Vit A) from one or more forms of malnutrition. About 60% Increased morbidity and mortality Figure 15.1 The intergenerational vicious cycle between undernutri- tion and poverty.

Food and Nutrition-Related Diseases 355 of the approximately 11 million deaths each year of childhood deaths. In some developing countries, children aged under 5 years in the developing world children die of AIDS-related diseases. HIV/AIDS is an are associated with malnutrition. In addition to the infectious disease that has pandemic proportions in undernutrition related to poverty, hunger, and food developing countries. It will be discussed in more insecurity, leading to stunted physical and mental detail here to illustrate the complex role of nutrition development, specific nutrient deficiencies are causes in this tragic situation. of specific diseases (as discussed in Chapters 4, 5, 8, and 9 of this textbook). The major nutrient deficiency 15.4 HIV/AIDS diseases prevalent in developing countries are briefly summarized in Box 15.2, to illustrate the scope of the Introduction problem and to identify the nutrition challenges in the developing world for the twenty-first century. Infection with HIV and the consequent development of AIDS is a global pandemic already responsible for Nutrition-related infectious disease in more than half of total deaths in some developing developing countries countries. It is estimated that since the early 1980s when the syndrome was described and the virus iden- Nutrition is a major determinant of the human body’s tified, this infectious disease has already killed more defense against infectious diseases. Optimal nutrition than 25 million people, including at least half a million is necessary for the integrity of the physical barriers children. A third of these deaths occurred in sub- (skin, epithelium) against pathogens. Specific nutri- Saharan Africa, where more than half of the 33.4–46 ents furthermore play important roles in defining million people currently infected with HIV live. The acquired immune function (both humoral and cell- pandemic has a devastating and tragic social, eco- mediated responses) and to influence, modulate, or nomic and demographic impact on previous devel- mediate inflammatory processes, the virulence of the opment and health gains in developing countries. It infectious agent, and the response of cells and tissues affects mostly young, sexually active adults in their to hypoxic and toxic damage. reproductive years as well as babies born from infected mothers. To understand the nutritional challenges of The immune system and the influence of malnutri- HIV/AIDS it is necessary to understand how the virus tion on its functions are discussed in detail in the is transmitted and to follow the clinical course of the clinical nutrition textbook of the series. Given the infection. The virus characteristics, its binding to cell high prevalence of malnutrition (undernutrition) in surface receptors, its entry into cells of the immune developing countries, it is not surprising that infec- system, its replication and transcription, as well as its tious diseases are still dominating mortality statistics genetic variability, and different classes of the virus in these countries. In children under 5 years of age have been intensively researched and described, these are diarrhea and common childhood illnesses in which malnutrition could lead to premature Box 15.2 Nutrient deficiency diseases in developing countries: prevalence (scope) Nutrient Consequence: disease Estimated: 1995–2006 Iron Anemia; poor brain development in infancy Maternal anemia pandemic: more than 80% in some Protein, energy countries; globally, more than 2000 million people Vitamin A Kwashiorkor, marasmus marasmic kwashiorkor, wasting Blindness; increased mortality from infectious diseases Millions of children are at risk Iodine 140–250 million children suffer from subclinical deficiency (children under 5 years especially vulnerable) Zinc Goiter, cretinism (infants) with severe brain damage and In 1999, 700 million people in developing countries; remarkable progress made with universal salt iodization mental retardation Its role in stunting and life-threatening childhood illnesses Thought to be common in children and during pregnancy is only now becoming clear

356 Introduction to Human Nutrition forming the basis for the development of antiretrovi- in developing countries may increase vulnerability to ral drugs to treat HIV/AIDS. More about this can be infection: the hopelessness and despair of poverty found in the clinical nutrition textbook of this series could lead to alcohol abuse, violence, rape, and irre- or at http://en.wikipedia.org/wiki/HIV. sponsible sexual behaviors, increasing exposure to the virus. In addition, malnutrition could compromise Transmission of HIV the integrity of the immune system, increasing vul- nerability to infection. Breaking this cycle by appro- Because there is still no vaccine against HIV and no priate public health nutrition interventions in poverty cure available, the emphasis is on prevention of trans- alleviation programs may indirectly also impact on mission of the virus. It is transmitted from person to HIV transmission. person via certain body fluids: blood (and blood products), semen, pre-seminal fluid, vaginal secre- ● Stage 1: Incubation period tions, and breast milk. There are no symptoms during this stage and its duration is usually 2–4 weeks. The majority of HIV infections are acquired through unprotected sexual contact when sexual ● Stage 2: Acute infection (seroconversion) secretions of one partner come into contact with There is rapid viral replication during this stage. It genital, oral, or rectal mucous membranes of another. may last from a week to several months with a mean The estimated infection risk per 10 000 exposures duration of 28 days. The symptoms in this stage (without a condom) to an infected source varies from include fever, lymphadenopathy, pharyngitis, rash, 0.5 to 50, depending on the type of exposure. myalgia, malaise, headache, and mouth and esoph- ageal sores. The blood transmission route is responsible for infections in intravenous drug users when they share ● Stage 3: Asymptomatic or latency stage needles with contaminated persons. Although blood This stage may last from a few weeks up to 10 or 20 and blood products are these days mostly checked for years, depending on the nutritional status and drug HIV, unhygienic practices in some developing coun- treatment of the individual. It is characterized by tries, needle prick injuries of nurses and doctors, as none or only a few symptoms, which may include well as procedures such as tattoos, piercings, and subclinical weight loss, vitamin B12 deficiency, scarification rituals pose some risk for infection. changes in blood lipids and liver enzymes, and an increased susceptibility to pathogens in food and Transmission of the virus from an infected mother water. to her child can occur in utero during pregnancy, during childbirth (intrapartum), or during breast- ● Stage 4: Symptomatic HIV infection feeding. The transmission rate between untreated CD4+ cell counts (the immune cells containing the infected mothers and children is approximately 25%. CD4 receptor, which binds the virus and which is This risk can be reduced to 1% with combination destroyed during viral replication) have decreased antiretroviral treatment of the mother and cesarean from normal values of 1200, to between 200 section. The overall risk of a breastfeeding mother to and 500 cells/µl.Wasting is a characteristic symptom child is between 20% and 45%. Recent studies have and is defined as an involuntary loss of more shown that this risk can be reduced three- to fourfold than 10% of baseline body weight. Other symptoms by exclusive breastfeeding for up to 6 months. Exclu- include loss of appetite, white plaques in the sive breastfeeding for 6 months is therefore the present mouth, skin lesions, fever, night sweats, TB, recommendation from the WHO for infected mothers shingles, and other infections. Nutrition interven- in developing countries “unless replacement feeding tions may help to preserve lean body mass, is acceptable, feasible, affordable, sustainable and safe “strengthen” the immune system and slow progres- for them and their infants before that time.” sion to stage 5. The clinical course of HIV infection: ● Stage 5: AIDS progression to AIDS The CD4+ counts are now below 200 cells/µL. The immunosuppression is severe and leads to many The different stages of HIV infection dictate different possible opportunistic or secondary infections with types of nutritional intervention. Even before infec- fungi, protozoa, bacteria and/or other viruses. tion, the vicious cycle of undernutrition and poverty

Food and Nutrition-Related Diseases 357 Malignant diseases and dementia may develop. This Box 15.3 Nutritional recommendations for HIV/AIDS is the final stage, and if not treated by antiretroviral drugs and specific drugs for the secondary infec- 1 Nutrition recommendations should do no harm tions it invariably leads to death. 2 Optimum nutrition at population level is necessary as part of a Nutrition and HIV/AIDS set of general measures to reduce the spread of HIV and TB 3 The focus should be on diversified diets including available, The role of nutrition in HIV/AIDS is complex. As mentioned above, malnutrition could contribute to affordable and traditional foods. However, fortified foods as increased vulnerability to infection in developing well as macro- and micronutrient supplements at safe levels countries. The virus probably increases nutritional (not more than twice daily recommended level) may be helpful needs, while its effects on the nervous and digestive 4 Ready-to-use therapeutic food supplements are effective in system lead to decreased appetite and intakes, reversing poor nutritional status found in severely affected indi- impaired digestion, and malabsorption. The conse- viduals quent loss of lean body mass gave the infection its 5 Because micronutrient deficiencies may hasten disease progres- original African name of “thin disease.” There are sion and facilitate mother-to-child transmission of HIV, multi- indications that improved nutrition may slow the vitamin, zinc and selenium supplementations are indicated, but progression of HIV infection to AIDS. There is evi- vitamin A supplementation may increase mother-to-child trans- dence that nutritional support can help in the toler- mission and zinc supplementation may be harmful in pregnant ance of antiretroviral drugs and their side-effects and women assist in the management of some of the secondary 6 HIV-infected pregnant women, lactating mothers and their infections of AIDS. babies need special advice and care to ensure best possible outcomes The optimal diet for people living with HIV/AIDS 7 Established, well-described steps and protocols should be fol- is not known. At least one study (the THUSA study lowed in public health nutrition interventions and in the thera- in South Africa) indicated that asymptomatic infected peutical (medical) nutritional support of patients subjects who regularly included animal-derived foods in their diets had better health outcomes than those General Principles from ASSAf (2007). on plant-based diets and with high omega-6 polyun- saturated fat intakes. The nutritional recommenda- Box 15.4 Types of nutrition interventions needed tions for people living with HIV/AIDS are therefore evidence informed and not totally evidence based at Stage Nutrition intervention needed this stage. Global recommendations have recently Poverty/malnutrition been evaluated by the Academy of Science of South cycle Public Health Nutrition (PHN) pro- Africa, and some of their conclusions are summarized grams as part of other programs to in Box 15.3. Increased vulnerability alleviate poverty and improve socioeconomic development The transmission of the virus and the different Decreased stages in the progression of infection to AIDS indicate immunocompetence Targeted nutrition (TN) programs that different levels of nutrition intervention and for vulnerable groups including support are needed, as illustrated in Box 15.4. Specific Transmission advice to pregnant mothers nutrient requirements during HIV infection are High risk behavior discussed in the clinical nutrition textbook of this Asymptomatic HIV TN programs for PLWH, including series. People living with HIV food assistance; food-based dietary guidelines plus advice on safe 15.5 The global challenge to address (PLWH) foods and drinking water malnutrition AIDS Individual therapeutic or medical Background nutrition (IMN) programs: i Facility based IMN programs The nutritional problems and diseases facing mankind at the beginning of the twenty-first century have been with defined algorithms ii Home-based care IMN programs with practical advice Food and supplement assistance

358 Introduction to Human Nutrition identified and briefly discussed in this chapter. In to regularly access, at affordable prices, adequate developed countries these are mainly childhood and (enough, sufficient), safe (uncontaminated), and adult obesity and the NCDs related to a combination nutritious food to prevent undernutrition and to of overnutrition, lack of activity, smoking, alcohol ensure optimal nutritional status for health, well- abuse, and stressful lifestyles. In developing countries being, a quality life, ability to actively and produc- the magnitude of undernutrition is staggering. tively work and play, and moreover to reach their Moreover, obesity and NCDs have emerged in these mental and physical development potential. This is countries and are increasingly becoming major causes often defined as being food and nutrient “secure.” of mortality. This double burden is further exacer- bated by the HIV/AIDS pandemic. The above situation would be possible if all stake- holders in the global community (UN agencies, gov- Dietary patterns responsible for ernments, NGOs, food industries, academics, civil the problems society, and others) worked together in partnerships to create a food and nutrition environment in which The dietary patterns and nutrient intakes responsible healthy food choices were available, acceptable, and and contributing to these problems have been inten- affordable and where consumers were educated, sively researched in epidemiological, clinical, and informed, and motivated to make the right choices. basic molecular studies. There is a huge body of sci- entific evidence available to identify the immediate But we do not live in an ideal world, as the high deficiencies and excesses in intakes, as well as all the prevalences of nutrition problems indicate. So the environmental factors associated with suboptimal questions that need to be answered are what should dietary patterns that lead to the nutrition-related dis- be done and by whom to rectify the situation? eases highlighted in this chapter. Broadly, these dietary problems can be summarized as: Clearly, the time for individual, separate programs to address undernutrition in one way and overnutri- ● hunger and food insecurity in developing coun- tion and NCDs in another is past. What is needed is tries, with infants, pregnant women, and older a holistic, integrated approach that will promote and people being the most vulnerable make optimum nutrition possible. Several UN agen- cies, separately or in combination have developed ● “hidden hunger” or micronutrient deficiencies in “strategic directions” and described policy principles, both developed and developing countries, espe- strategies to introduce this on different levels in dif- cially of iron, vitamin A, zinc, iodine, and all dietary ferent settings, as well as actions to promote healthy antioxidants diets. The challenge is huge, for there are many bar- riers to overcome: from war, to uncommitted political ● overconsumption of unfortified and refined staple agendas, to “unhealthy” food preferences of individu- foods in “low-quality diets” als. The lessons learned from the failure of many developing countries to be on-track in reaching the ● availability and intake of too many high-fat, sugary, Millennium Development Goals by 2015 plead for a and refined convenience and fast foods, increasing new approach and global leadership. This could be total fat, saturated fat, trans fat, omega-6 fatty acid, possible in partnerships in which there is recognition sugars, and salt intake and respect for different agendas, but where partners are willing to develop a common nutrition agenda ● not enough fish and other sources of omega-3 fatty and agree on steps to reach common goals. But there acids in the diet are also many success stories. For example great strides have been made in the past few decades to ● not enough vegetables and fruit and their products reduce child undernutrition in some developing in the diet regions. A global database on child growth and mal- nutrition covers 95% of the world’s under-5 popula- ● not enough dietary fiber-rich foods in the diet; tion (http://www.who.int/nutgrowthdb). Much is ● too little dietary variety being done by several UN agencies and international ● over-reliance on dietary supplements in the devel- donors and NGOs to improve the global nutrition situation, assisting countries in nutrition surveillance oped world. Suggestions to meet the challenge In an ideal world, every human being would be able to exercise their right (often constitutionally defined)

Food and Nutrition-Related Diseases 359 Box 15.5 UN Agencies: Intersectorial nutrition policies and assistance of displaced people to educating consum- strategies to address the double burden of nutrition problems ers how to choose healthy diets. The development of throughout the life course food-based dietary guidelines in both the developed and developing world to assist people to choose an 1 Nutrition surveillance adequate but prudent diet for optimal nutrition is an 2 Combating micronutrient deficiencies example of the latter. There is total agreement in the body of literature on the nutrition challenges of the • Fortification twenty-first century that the focus should be on pre- • Salt iodization vention of nutrition-related diseases to minimize 3 Nutrition advocacy their serious economic and social consequences. 4 Developing national food-based dietary guidelines 5 Addressing nutrition and HIV/AIDS Further reading 6 Addressing obesity and other diet-related diseases 7 Improving maternal, infant and young child nutrition cycle ASSAf. HIV/AIDS, TB and Nutrition. Scientific inquiry into nutri- Improving nutrition of school-age children and adolescents tional influences on human immunity with special reference to (integrated school-based program, nutrition friendly schools, HIV infection and active TB in South Africa. Pretoria, Academy health promoting schools) of Science of South Africa, 2007: 1–283 (www.assaf.org.za). • Ensuring appropriate fetal development • Implementation of new growth reference Murray CJ, Lopez AD, eds. The Global Burden of Disease. A • Improving infant and young child nutrition (breastfeeding, Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1999 and Projected to 2020. complementary feeding, baby-friendly hospitals, global Geneva, Harvard University Press and WHO, 1996: 1–989. strategy on infant and young child feeding). Standing Committee on Nutrition (SCN). Working together to end and implementation of targeted programs. In Box child hunger and undernutrition. SCN News 2007; 34: 1–80. 15.5 one such an example is given, namely the topics of the WHO’s integrated and intersectorial food poli- United Nations Administrative Committee on Coordination, Sub- cies and strategies to address the double burden of Committee on Nutrition (ACC/SCN), in collaboration with the nutrition problems throughout the life course. International Food Policy Research Institute (IFPRI). 4th Report of the World Nutrition Situation: Nutrition Throughout the Life There is agreement that policies and programs Cycle. Geneva, IFPR, 2000. should be implemented at all “levels” – from global macrolevels to individual microlevels. These pro- World Cancer Research Fund and American Institute for Cancer grams will include a variety of actions – from food Research. Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective. Washington DC, AICR, 2007. World Health Organization. Global Strategy on Diet, Physical Activity and Health. Diet, Nutrition and the Prevention of Chronic Diseases. WHO. Technical Report Series, no 916. Geneva, WHO 2007: 1–149 (http://www.who.int/dietphysicalactivity/ publications/trs916/en/).



Index Note: page references in italics refer to information in impact on cholesterol 119–20 figures or tables. properties 98 appetite 33–4 abdominal girth 25 hormonal regulation 35 acetyl-CoA 105–7, 178–9 metabolic factors 35 acidity regulators 348 neurophysiological factors 34–5 acrylamide 344 arachidonic acid cascade 109–11, 110 additives 10, 346–7, 348 arginine 51, 52, 60 arginine—nitric oxide pathways 54 regulation 299–300 arsenic 233–4, 236, 344 sodium-containing 200 ascorbic acid see vitamin C adipose tissue 15 asparagine 52 component lipids 104 aspartate 51, 52 aspartic acid 57 and dietary fat intake 106 assessment of nutritional status see nutritional status assessments endocrine control 103 astroviruses 334 aflatoxins 345 atherogenic lipoprotein phenotype (ALP) 103 agricultural residues 10 atherosclerosis AIDS/HIV 355–7 and homocysteine levels 174 nutrition needs 61, 357 lipid-mediated 100, 102–3 alanine 51, 52 albumin 214 cholesterol-lowering drugs 91, 95 aluminium 233–4, 236 nutritional modifications 103–4 Alzheimer’s disease 215 postprandial lipemia 98 amino acids TAG regulation hypothesis 103–4 biochemical roles and functions 50, 51, 63 athletes, energy requirements 43 ATP production 77 discovery and history 50–1 avidin 177 homeostasis and turnover 58–61, 78 metabolic needs 58–64 Bacillus cereus 328, 330 metabolites and derivatives 53–4 bacterial contamination 10, 327 biochemical structures 51–4 body requirements 66–7 emerging pathogens 326–7 by species 62 pathogen characteristics 328–33 estimation and determination 65–7 toxins 345 in catabolic states 62, 72 Bartter’s syndrome 196 influencing factors 58, 71–2 basal metabolic rate 37–8 meeting needs 67–9 and energy intake ratios 269–70 classification 54–8 beriberi 153–4 sources 56–7 bias 260–3 digestibility 68–9 bile acids 95 ammonia 56–7, 61–2 bioactives 291 amylopectin 80 bioavailability of foods, defined 286–7 amylose 80 biochemical markers 130 anemia bioelectric impedance 25–6 iron-deficiency 207 bioflavonoids 186 megoblastic 175 biological markers 130 pernicious 168, 169 biotin 176–8 and folate 175 deficiencies 177 and scurvy 183 functions 177 and vitamin B12 168, 169 blood clotting, and vitamin K 150–2 animal meat blood glucose, regulation mechanisms 77–9 dietary fats 91–2 body composition 12–30 drug residues 343 levels animal studies 311–14 anthropometry 22–3 atomic 13 antioxidants 291 cellular 14 intracellular 61 molecular 13 mode of action 222 relative relationships 14–15 apoproteins 97, 99 whole body 14

362 Index Campylobacter 331 cancer body composition (cont.) measurement techniques 15–27 and folate 174–5 advantages and disadvantages 27 and selenium 219 anthropometry 22–3 and vitamin B6 164 bioelectric impedance 25–6 and vitamin C 185, 219 carcass analysis 15–16 carbohydrates 74–85 creatinine excretion 26–7 classes 74–5 CT imaging 21–2 digestive breakdown and absorption 74–6 densitometry 16–18 dilution methods 18–19 fermentation in the colon 82–3 dual-energy X-ray absorptiometry (DEXA) 18, 19– of short-chain fatty acids 83–4 21 food sources 76 infrared interactance 25 malabsorption problems 75–6 MRI imaging 22 metabolic utilization 77 multicompartment models 20–1 oral pH and dental caries 84–5 N-methyl-histidine excretion 26–7 types skinfold thickness 23–4 glycemic 76–9 total body electrical conductivity (TOBEC) 26 nonglycemic 79–84 ultrasound 25 resistant starch and dietary fibre 81–2 in vivo neutron activation analysis 16 carbon recycling 107 weight/height indices 22–3 carcass analyis 15–16 prospects for future 29–30 cardiovascular disease 351–3 use and misuse of data 27–9 and homocysteine levels 174 and lipids body fat ALP findings 102–3 biochemical components 104 cholesterol-lowering drugs 91, 95 deposition sites 104 homeostasis and transport 95, 100–3, 102–3 measures 27–9 hormonal control 103 comparative analysis 29 nutritional modifications 103–4 densitometry 16–18 postprandial regulation 98 skinfold thickness 23–4 triacylglycerol (TAG) hypothesis 103–4 see also adipose tissue carnitine 186 carotenoids 135–7, 291 body mass index (BMI) 22–3 antioxidant function 139 obesity measures 45 see also vitamin A case-control studies 318, 320 body protein mass 58 cassava 346 bone mass, and calcium 191–2 cell membranes 90–1, 104 boron 233–4, 236 cell signaling mechanisms, arachidonic acid cascade 109–11, 110 bowel cancer ceruloplasmin 214 cestodes 338 prevention chemicals affecting foods 340–6 folate supplements 174–5 acceptable intake levels 341–2 role of butyrate 84 classes 340 chemotherapy, and folate supplements 172–3 Boyle Gay-Lussac’s law 17–18 children brain energy requirements 42 malnutrition 299 and lipids 105, 114–15 chloropropanols 344 role of docosahexaenoate 114 cholecystokinin (CCK) 34, 93 cholera 332 bread/flour, fortified 174, 193 cholesterol 86 BSE (bovine spongiform encephalopathy) 338–9 biliary 95 bulking agents 348 biosynthesis 114–15 burning foot syndrome 179–80 dietary intake 116–17 butyrate 83–4 impact on blood lipids 115–16 role of MUFAs 116 cadmium 233–4, 236, 344 sources 90, 91–2, 114–15 calcitriol 143–4 dietary regulation cf. drug lowering regimes 117 calcium 189–94 functions, brain lipid membranes 105, 114–15 homeostasis 95 absorption and transport 189–91 genetic factors 119–20 influencing factors 191 hormonal control 103 LDL receptor pathways 100–1, 102–3 daily requirements 193–4, 194 HDL reverse transport pathways 101–2, 102–3 food sources 193–4, 193 functions 191 deficiency conditions 191–2 homeostatic regulation 190 interactions 194 nutritional status 192–3 tissue distribution 189–91 toxicity 192 and vitamin D 144, 192

re-esterification processes 96 Index 363 role of plant sterols 91, 116 triacylglycerol (TAG) hypothesis 103–4 cystic fibrosis 114 storage, structural pools 104 cystine 52 cholesterol-lowering drugs 117 cytochrome C oxidase 214 effectiveness 117 mode of action 95 daily nutrient recommendations see dietary reference and plant sterols 91, 116 standards choline 186 chromium 230–2 data accuracy and validity 247–8, 266–8, 305–6 chylomicrons 97–8, 100 data analysis 305–10 properties 98 densitometry 16–18 chyme 93 dental caries clinical trials 318 Clostridium botulinum 328 and fluoride 229–30 Clostridium perfringens 330 role of carbohydrates 84–5 cobalamins 167–70 depression, and food intake 35 Codex Alimentarius Commission (CAC) 299–300 desaturation processes 108–9 coding systems 262 developing countries 353–5 coenzyme A (CoA) 178–9 impact of HIV/AIDS 355–7 coenzyme Q 187 infectious disease 355 cohort studies 318, 320–1 nutrient deficiencies 354–5 colon obesity and NCDs 354 bacteria 82–3 poverty and malnutrition 353–4 carbohydrate breakdown 79–84 DHA see docosahexaenoate colorectal cancer diabetes 78, 351–3 prevention and dyslipidemia 103 butyrate 84 and vitamin D status 144 folate supplements 174–5 diet history information 259–60 community nutrition, clinical roles 7 see also nutritional status assessments community trials 318 diet quality assessments 272 composite dishes, food composition calculations 287–8 diet-induced disease see nutrition-related diseases congenital hyperthyroidism 224 dietary assessment methods see nutritional status assessments conjugated fatty acid isomers 90 dietary data, accuracy and validity 247–8, 266–8 CONSORT guidelines 315 dietary fats 90, 92 contaminants see bacterial contamination; chemicals affecting digestion and absorption 92–8 nutritional and metabolic effects 112–14 foods; viruses and foods see also lipids copper 212–17 dietary fiber 81–3, 116 intake levels 82 daily requirements and sources 216–17 dietary patterns 294–5, 358–9 functions 213 dietary reference standards 122–31 concepts and approaches 122–3 deficiency conditions 213–14 enzyme components 181, 213, 214 changes to 125 genetic diseases 215–16 definitions and terminology 123–5 interactions 217 future studies 131 metabolism and absorption 213 identification methods 128–31 nutritional status measures 216 supplements 111 animal experiments 130–4 toxicity 214–15 balance studies 129 transport and tissue distribution 213 biochemical markers 130 corneal conditions 140 biological markers 130 coronary heart disease, fish oil supplementation 117–18 deprivation studies 128–9 correlation 310 factorial methods 129–30 coxsackie viruses 334 radioactive tracer studies 129 creatine 53 tissue nutrient level measures 130 creatinine 61 interpretation and uses 125–7 excretion 26–7 for population studies 127–8 cretinism 224 digestion Creutzfeldt-Jakob disease (CJD) 339–40 carbohydrates 74–6 cross-sectional studies 318, 320 fats 92–8 Cryptosporidium parvum 339 food intake regulation 34 CT imaging, body composition analysis 21–2 proteins 68–9 cultural beliefs 8 dihydrofolate reductase 172–3 cyanide 10 dioxins 343 Cyclospora cayetanesis 339 disaccharides 80 cysteine 51, 52, 54, 61 disease body energy needs 44 evolutionary perspectives on diet 114 food-borne illnesses 325

364 Index ethnicity BMI and body fat analysis 23 disease (cont.) food patterns 291 global challenges 350–9 in developed countries 351–3 Europe in developing countries 353–5 food safety regulation 302–3 nutrient intake goals 352–3 public health policies 303–4 docosahexaenoate 118 European Food Safety Authority (EFSA) 302–3 early brain development 114 exercise, and energy balance 43 experimental diets 314–15 dopamine 53 double labeled water (DLW) measures 39–40, 269 Fanconi’s syndrome 199 Down’s syndrome 216 fat-free mass (FFM), density calculations 17 dual-energy X-ray absorptiometry (DEXA) 18, 19–20 fats see dietary fats; fatty acids; lipids fatty acids multicompartment models 20–1 dUMP suppression test 175–6 classification and terminology 87–90 Duncan test 309 dietary intake dyslipidemia 103 effects on serum cholesterol 115–16, 119 echovirus 334 imbalances of n-3 to n-6 117–18 ecological studies 318, 321 trans fatty acids 113, 116 eicosanoids 109–11 digestion and absorption 92–3 eicosapentaenoic acid 117–18 and colonic fermentation 83–4 elderly metabolism biosynthesis 105–6 energy requirements 42 desaturation 108–9 height/weight measures 24 hydrogenation 109 emulsification processes 92–3 ketogenesis and ketosis 107 emulsifiers 348 oxidation 106–7 energy availability, carbohydrate metabolism 77 peroxidation 107–8 energy balance role of eicosanoids 109–11 concepts and definitions 31–2 nutritional and metabolic effects 112–14 components 32–3 deficiencies 113–14 future perspectives 47–8 impact of trans fats 113 in disease and trauma states 44 storage 104–5 in infancy and childhood 42 as body fat 104 in old age 42 whole body profiles 105 in physically active individuals 43 transport and circulation 95–8, 100–4 in pregnancy and lactation 43 see also lipids measures 268–71 fermentation processes, colonic 82–3 energy expenditure 35–40 ferroxidase 214 concepts and definitions 32–3, 35–6 fiber historical aspects 36 dietary 81–3 influencing factors intake levels 82 field trials 318 physical activity 39 fish resting metabolic rate 37–8 dietary fats 92, 117–18 thermic effects of feeding 38–9 parasites 338 measurement 36–7, 268–71 poisoning 347 double labeled water (DLW) 39–40, 269 toxins 345–6 urinary nitrogen measures 268–9 FIVIMS (Food Insecurity and Vulnerability Information and energy intake 32, 33–5 dietary sources 33 Mapping System) 6 influencing factors 34–5 flavins 155–8 regulation mechanisms 33–4 flavonoids 291 energy requirements 40–2 flavor enhancers 348 Entamoeba histolytica 339 flukes 336–7 enterohepatic circulation 95 fluoride 228–30 environmental contaminants 10, 343–4 epidemiological designs 316–22 daily requirements and sources 230 cross-sectional studies 320 functions 229 experimental studies 316–19 non-experimental studies 319–20 deficiency symptoms 229 error 246–7 metabolism and absorption 228–9 recall problems 263–4 toxicity 229–30 sources 260–2 folic acid 170–6 essential fatty acid deficiencies 113–14 daily requirements 175 estrogen 103 equivalents and viamers 170–1 ethics and nutrition studies 317 functions 171–5

metabolism and absorption 171 Index 365 tissue uptake 171 concerns and contributing factors 324–7 nutritional status assessment 175–6 bacterial pathogens 10, 327, 328–33 food additives 10, 200, 346–7 changing supply systems 324–5 chemical contaminants 340–6 regulation 299–300 emerging pathogens 326–7 Food and Agriculture Organization (FAO) 6 food additives 346–7 food-borne illnesses 325–6 food classification systems 280 parasites 335–8 food composition data 262, 276–92 prion diseases (BSE/vCJD) 338–40 setting safe intake levels 341–2 benefits and uses 277 toxins 344–6 criteria for inclusion 278 virus contaminants 327, 334–5, 334 descriptions and classification of foods 278–9 control programmes 348 sampling methods 279–81 European regulation 302–3 data analysis methods 282–4 future studies 304, 348–9 data presentation 283–4 surveillance systems 325 data quality 284 UN/UN agencies regulation 298–300 data sources 284–5 food sampling, for food composition tables 279–81 future studies 289–92 food supply problems system changes 324–5 bioavailability 286–7 trade agreements and tariffs 300–1 composite recipes 287–8 food-borne illnesses 325 food preparation effects 285–6 bacterial contamination 327, 328–33 missing values 286 economic consequences 326 portion estimates 288 emerging pathogens 326–7 retrieval of data 288–9 parasite infections 335–8 food—nutrient data conversion 289 surveillance 325 see also food labeling and profiling virus contamination 327, 334–5, 334 food diaries 249–53 vulnerable groups 325 Food and Drug Administration (FDA) 279 formiminoglutamate test (FIGLU) 175 food frequency questionnaires 256–9 fructooligosaccharides (FOSs) 82 food intake fructose 75, 76–7, 79 assessments 272–3 functional foods 10, 82, 291, 296 of dietary adequacy 272 fungal toxins 345 measures fungicides 342–3 choice of method 265–6 direct 244–60 galactose 75–6 evaluating data 271–2 gene expression regulation indirect 239–44 sources of error 260–5 role of fatty acids 120 underreporting 271–2 role of retinol 137 validity and repeatability 266–71 genetics, blood lipid metabolism 119–20 regulation 33–5 germanium 233–4, 236 appetite and satiety 33–4 ghrelin 35 central nervous system factors 34–5 Giardia intestinalis 339 circulatory factors 35 glucose 36 digestive factors 34 absorption 75–6 external signals 35 metabolism 77 peripheral signals 35 thermic effects 38–9 role of biotin 178 food labeling and profiling 296, 297–8 rate of uptake 76–7, 78 food policy and regulation 293–304 regulation 77–9 base-line dietary patterns 294–5 making changes 295–6 and diabetes 78 communication and policy dissemination 296–8 glucose-galactose malabsorption syndrome 76 nutrition claims 297 glucosinolates 291 nutrition labeling 296–8 GLUT proteins 75–6 European agencies 301–4 glutamate 51, 52, 56–7 UN and UN agencies 298–9 glutamine 50, 51, 52, 56–7 WHO/FAO and Codex Alimentarius 299–300 glutathione 61 WTO sanitary measures and trade barriers 300–1 glycemic index (GI) 78–9, 186–7 food preparation, nutrient losses 285–6 glycine 51, 52, 54, 56–7 food processing, contaminants 344 glycoalkoids 348 food profiling 297–8 glycogen 77 food safety 10, 324–49 glycolysis 77 assessments 273–4 glycosides 348 goitre 224

366 Index Graves’ disease 225 genetic diseases 225 growth, amino acid and protein needs 55, 62–3 interactions 225–6 gum arabic 116 metabolism and absorption 223 nutritional status measures 225 hazardous substances 10 toxicity 224–5 health status, and nutrition 4 transport and tissue distribution 223 heavy metals 10, 343–4 iron 205–9, 355 hemochromatosis 208 daily requirements 208–9 hepatitis E 334–5 food sources 208–9 hepatitis-A virus 327, 334 functions 206–7 herbicides 342–3 high-density lipoproteins (HDL) 98–9 deficiency symptoms 207 genetic diseases 208 properties 98 interactions 209 reverse cholesterol transport 101–2, 102–3 metabolism and absorption 205–6, 207 histidine 51, 175–6 history of nutrition science 7–9 role of vitamin C 184–5 HIV/AIDS 355–7 nutritional status measures 208 nutrition needs 61, 357 toxicity 207–8 homocysteine 53, 173–4 transport and tissue distribution 205–6 elevated levels 174 isoflavones 291 household surveys 243–4 isoleucine 51, 52 expenditure data 243 food account methods 243–4 JECFA (Joint FAO/WHO Expert Committee on Food Additives) food inventory methods 244 299–300 food procurement data 244 Human Genome Project 50 JEMRA (Joint FAO/WHO Meeting on Microbiological Risk human nutrition science see nutrition studies Assessment) 299–300 hunger 33–4 hydrogenation processes 90, 92, 109 Kaplan-Meier estimates 309 partial 92, 109, 113, 116 Kashan-Beck disease 218–19 hydroxylases, and vitamin C 181–2 Kayser-Fleischer rings 215 hypercalcemia 192 Keshan’s disease 218–19 hypertension, and homocysteine levels 174 ketogenesis 107 hyperthyroidism 225 ketosis 107 hypocalcemia 195 Kruskal-Wallis test 309 hypokalemia 195 kynureninase 165–6 hypophosphatemia 199 hypothalamus 34–5 lactation, energy requirements 43 hypothesis testing 307 lactose 75 hypothyroidism 224, 225–6 intolerance 75 in vitro studies 310–11 LanguaL 279, 280, 283–4 in vivo neutron activation analysis (IVNAA) 16 lead 233–4, 236 incidence, defined 322 industrial contaminants 343–5 toxicity 344 industrial pollution 10 lecithin 90 infants lectins 346 leptin 35 energy requirements 42 leucine 51, 52, 53, 161 and vitamin B6 165 leucovorin rescue 173 and vitamin D 144–5 leukotrienes 109–11 INFOODS (International Food Data System Project) (UN) 273, linoleate 104, 106, 108, 109, 113, 117, 118 279, 283–4, 290 deficiencies 114 informed consent 317 lipemia, postprandial 97–8 infrared interactance 25 lipids 86–120 inositol 186–7 insecticides 342–3 background history 86–7 insulin 35 classification and types 87–91 functions, lipoprotein metabolism 103, 104 circulating 98–104 intestinal flukes 336–7 fats and oils 90 iodine 223–6 hydrogenated and conjugated fatty acid isomers 90 long-chain saturated and monounsaturated fatty acids 89 daily requirements 225 medium- and short-chain fatty acids 88 food sources 225 milk and plasma lipids 105 functions 223–4 phospholipids 90–1 polyunsaturated fatty acids (PUFAs) 89 deficiency symptoms 224, 355 saturated fatty acids 87–8 simple lipids 87 sterols 91 unsaturated fatty acids 87–8

dietary intake 92 Index 367 dietary sources 91–2 digestion and absorption 92–4 targets and initiatives 6, 298–300 metabolism (long-chain fatty acids) 105–11 UN/UN agency responses 298–9 manganese 226–7 role of eicosanoids 109–11 Mann-Whitney U-test 309 solubilization 93–4 meat storage and deposition 96–8 dietary fats 91–2 drug residues 343 body lipid pools 104–5 overcooked 344 whole body fatty acid profiles 105 Mediterranean diet 116, 117 structural and cell membrane functions 90–1, 104 medium-chain fatty acids 88–9, 112 transport 95–8, 96 dietary sources 92 HDL reverse cholesterol pathways 101–2, 102–3 megoblastic anemia 175 LDL receptor pathways 100–1, 102–3 memory, recall errors 263–4 lipolysis 93 menadiol 149–50 lipoprotein lipase (LPL) 98 menaquinone 149–50 lipoproteins 92 Menkes’ syndrome 215 assembly and secretion 96–7 mercury 344 classification and distribution 98, 99 meta-analysis 322 VLDLs 98–103 metabolic rates, at rest 37–8 homeostasis 95, 100–3 methionine 51, 52 structures and metabolism 95, 98–9 load test 165–6 metabolic determinants 100 metabolism 172, 173–4 transport pathways 99–100, 102–3 methyl-folate trap 173–4 Listeria monocytogenes 330 methylmalonic aciduria 170 lithium 233–4, 236 microbial toxins 344–5 liver, cholesterol homeostasis 95, 100–3, 101, 102 milk 193 liver flukes 336 sunlight exposure 155 long-chain fatty acids 89 milk lipids 105 dietary sources 92 Millenium Development Goals 6, 299, metabolism biosynthesis 105–6 358 carbon recycling 107 minerals and trace elements 188–237 desaturation 108–9 hydrogenation 109 definitions 188 ketogenesis 107 future study areas 232, 236–7 oxidation 106–7 periodic table 189 perioxidation 107–8 ultratrace elements 232–6 role of eicosanoids 109–11 molds and toxins 345 nutritional regulation 111–12 molybdenum 227–8 low energy reporters (LERs) 270–1 monosaccharides 75, 80 low-density lipoproteins (LPLs) monounsaturated fatty acids (MUFAs) 89, 113, 116, hormonal control 103 influence of dietary fats 115–16 117 properties 98 motor neurone disease 216 receptor pathways 100–1, 102–3 MRI techniques, body composition analysis 22 lung flukes 337 mRNA, protein synthesis 53 lysine 52 MUFAs see monounsaturated fatty acids (MUFAs) mycotoxins 345 mad cow disease 338–9 magnesium 194–7 NCDs (non-communicable diseases) see nutrition-related diseases daily requirements 196–7 food sources 197 nematodes 335–8 functions 195 neurotransmitters, synthesis 51 niacin 158–62 deficiency conditions 195–6 genetic diseases 196 classification and equivalents 159–60 homeostasis and absorption 194–5 daily requirements 162 interactions 197 nutritional status assessments 196 availability 160 tissue distribution 194–5 functions 161 toxicity 196 malabsorption syndromes 75–6 deficiency conditions 161–2 malaria, and riboflavin 157 metabolism and absorption 160–1 malnutrition global challenges and perspectives 5–7, 298–9, 357–9 catabolism 160 and poverty 353–4 urinary excretion 160–1 nutritional status assessment 162 toxicity 162 nickel 233, 235, 236 nicotinamide 159–60 nicotinic acid 159–60 night blindness 139

368 Index in developing countries 354 etiology 46 nitrogen health implications 103, 351–3 biochemical precursors 60–1 role of physical activity 46–7 body requirements 60, 64 observational studies 319–20 protein synthesis 56–7 oils 90 sources 56–7 oleate 104, 108, 113, 118 oligosaccharides 75, 80, 82 nitrogen cycles 56, 59, 59 omega fatty acids see polyunsaturated fatty acids (PUFAs) nitrosamines 344 ORAC database 291 oral contraceptives, and vitamin B6 166–7 and vitamin C 185 ornithine 53–4 nonglycemic carbohydrates 79–84 osteomalacia 144–5 nonstarch polysaccharide (NSP) see dietary fiber oxidation processes, fatty acids 106–7 noroviruses 327, 334, 334 oysters, pathogens 333 novel foods see functional foods nutrient recommendations see dietary reference standards PAHs 344 nutrients Paleolithic diets 114 palmitate 104, 108 dietary reference standards 122–31 pancreas, blood glucose regulation 77–8 food composition data 262, 276–92 pantothenic acid 178–80 labeling and profiling 296–8 see also carbohydrates; lipids; minerals and trace elements; non-nutritional uses 180 parasites 335–8 proteins; vitamins parathyroid hormone 144 nutrition claims 297 partially hydrogenated fatty acids 92, 109, 113, 116 nutrition labeling 296 patulin 345 nutrition studies 1–10 PCBs (polychlorinated biphenyls) 343 PDCAAS (protein digestability-corrected amino acid score) approaches 2 conceptual frameworks 2–3 69–70 development history 7–9 pectin 116 disease risk associations 294 pellagra 161–2 global perspectives 5–7 Pendred’s syndrome 225 and health 4 periodic table 189 key study components 4–5 pernicious anemia 168, 169 reference points 293–4 peroxidation (auto-oxidation) 107–8 research areas and challenges 9–10 pesticide residues 342–3 research methodology 305–23 pesticides 10 phenylalanine 51, 52 experimental design and statistical analysis 305– phospholipids 90–1, 104 10 phosphorus 197–200 future studies 322–3 food sources 193, 200 use of animal models 311–14 functions 198–9 use in epidemiological studies 316–22 use in human studies 314–16 deficiency conditions 199 use of in vitro studies 310–11 genetic diseases 199 scientific theory vs clinical practice 7 homeostasis and absorption 197–8 see also nutritional status assessments interactions 200 nutrition-related diseases nutritional status assessments 200 in developed countries 351–3 tissue distribution 197–8 in developing countries 353–5 toxicity 199 nutritional status assessments phylloquinone 149–50 considerations 238–9 phytate 346 direct measures of intake 244–60 phytestrogens 187 basic concepts and definitions 246–8 phytoceuticals 187 for longer periods 256–60 phytosterols 95 for specified days 248–56 food sources 92 future study areas 274 plant proteins 70–1 indirect measures of intake 239–44 plant sterols 91, 116, 291 approaches 240 plant toxins 346 commodity-level food supply data 240–2 plasma lipids household surveys 243–4 overview 105, 118 product-level food supply data 242–3 see also cholesterol; triacylglycerols (TAGs) method choice 265–71 polioviruses 334 repeatability and validity 266–71 pollutants see chemicals affecting foods safety assessments 273–4 polyhalogenated hydrocarbons (PHHs) 343–4 nutritionists, roles 7 polysaccharides 75, 80 obesity 44–7 basic metabolic principles 44–5 definitions 45 in developed countries 351–3

polyunsaturated fatty acids (PUFAs) 89 Index 369 basic functions 104 deficiencies 113–14 pyridoxines 162–4 desaturation 108–9 pyruvate 77 dietary intake 113 impact on serum cholesterol 115–16, 119 quality of diets 272 imbalances of n-3 to n-6 114, 117–18 quasi-experiments 318 n-3 deficiencies 113–14 questionnaires 256–9 nutrient—gene interactions 119–20 hydrogenation 109 recipes, food composition calculations 287–8 nutritional and metabolic effects 113–14 recommendations and standards see dietary reference standards clinical importance 114 records of food intake 248–53 nutritional regulation 111–12 reference values for nutrients see dietary reference standards oxidation and peroxidation 107–8 regional food differences 281–2 storage 104, 105 reliability of data 306 research methodology pooled analysis 322 pork, pathogens and parasites 333, 338 animal models 311–14 portion size estimates 263, 288 in vitro studies 310–11 potassium 202–5 statistical analysis 305–10 residues 342–4 body composition measures 19 resistant starch 81 daily requirements 204–5 response bias 260–2 food sources 204–5 resting metabolic rate (RMR) 37–8 functions 203–4 retinol 134, 135, 137 see also vitamin A deficiency symptoms 204 retinol binding protein (RBP) 137 homeostasis and absorption 203 riboflavin see vitamin B2 (riboflavin) interactions 205 rickets 144–5, 192 toxicity 204 rotaviruses 334 transport and tissue distribution 203 rubidium 233, 235, 236 poverty and malnutrition 353–4 power calculations 307–8 salivary glands 75 pregnancy Salmonella 332 and anticoagulants 151–2 salt intake trends 203 energy requirements 43 and folate 174 see also sodium and chloride prion diseases 338–40 sample size calculations 308 processed foods, partial hydrogenation processes 92 sampling bias 260 propionate 83–4 satiety 34 prostaglandins 109–11 saturated fatty acids 89 proteins 49–72 background and discovery 50–1 dietary sources 92 biochemical roles 51 nutritional and metabolic effects 112, 118 amino acid functions 50 and LDL cholesterol 119 biochemical structures 49 public health policies 296 biochemical synthesis and degradation 58–62 see also long-chain fatty acids body requirements 58–63, 64–5 SCFAs see short-chain fatty acids Schilling test 170 by age and physiological groups 58, 64–5 scurvy 182–3 dietary recommendations 63–5 seafood pathogens 332, 347 during illness and trauma 72 toxins 345–6 estimation 63–5 seed oils 91 influencing factors 58, 71–2 selenium 217–23 growth needs 55, 62–3 daily requirements 220–1 metabolic needs 58–64 food sources 220–1 over supply 61–2 functions 218 classification of amino acids 54–8 deficiencies 355 deficiency conditions 218–20 food sources 70–1 genetic diseases 220 and digestibility 68–9 interactions 221–3 and nutritional quality 69–70 metabolism and absorption 217–18 worldwide availability 71, 355 nutritional status measures 220 future considerations 72 toxicity 220 protozoa 338, 339 transport and tissue distribution 217–18 public health nutrition 9–10 selenoproteins 218, 219 role of nutritionists 7 serine 51, 52 PUFAs see polyunsaturated fatty acids (PUFAs) sex hormones, functions, lipoprotein metabolism 103 puffer fish 347 short-chain fatty acids (SCFAs) 83–4, 88 absorption 83–4 roles 83