Index 195

benzene, 87

beriberi, 64, 70

beverages, 47

bias, 129, 130

bicarbonate, 126, 143

bile, 63, 73, 156

binding, viii, xi, 11, 13, 21, 23, 24, 25, 36, 86, 88,

89, 90, 94, 97, 100, 103, 107, 108, 111, 112, 115,

116, 118, 124, 128, 172, 181

biochemistry, 25, 40

biodegradable, 172

biodegradation, 84, 87, 96

biological systems, 86

biomass, 92

biomedical applications, 161, 173, 174

Biopolymers, 170

bioremediation, xi, 82

biosynthesis, 41, 83, 100, 117

biotin, x, 51, 54, 58, 60, 134

bipolar disorder, 26

birth(s), 40, 43, 50, 55, 177, 186

birth weight, 40, 50, 177, 186

bladder, 128

bleeding, 32, 33

blindness, 27

blood, ix, xiii, 2, 23, 24, 26, 29, 31, 32, 33, 39, 43,

45, 47, 52, 56, 78, 134, 140, 143, 154, 156, 157,

162, 164, 165, 166, 172, 175, 176, 180, 182, 184

blood flow, 33, 154

blood pressure, 31, 33

blood stream, 33

blood supply, 154

blood vessels, 23, 164, 165, 180

body fat, 177

body fluid, 26

body weight, 27

bonding, 100

bonds, 23, 100, 102, 111

bone growth, 177

bone marrow, xiii, 175, 176, 181

bowel, x, 57, 58, 59, 60, 62, 70, 71, 72, 74

brain, 26, 28, 29, 33, 36, 43, 55, 140, 142, 143, 152,

155, 177, 179, 187

brain tumor, 55

branching, 86

breakdown, ix, 22, 27, 29, 124

breakfast, 52

Breast, 42

breast cancer, ix, 39, 46, 47, 53, 54

breathing, 25

broadband, 183, 190

buccal mucosa, 182

Budd-Chiari syndrome, 67

buffer, 104, 106, 110, 114

building blocks, 82, 83

butyl ether, xi, 81, 84, 85, 95, 96, 97

C

calcium, 60, 188

California, 55

campaigns, 43

Canada, 21, 48, 130, 137

cancer, v, viii, 5, 6, 7, 14, 15, 17, 21, 24, 40, 43, 46,

47, 49, 50, 53, 67, 68, 70, 71, 77, 78, 79, 124,

128, 132, 137, 155, 166

cancer cells, viii, 6, 14, 15, 17

candidates, 70

capillary, 75

carbon, xii, 41, 83, 84, 86, 87, 89, 91, 92, 93, 95, 97,

105, 111, 112, 131, 139, 140, 141, 143

carbon atoms, 41, 84, 87, 97, 105

carbonic acids, x, 81, 84, 87

carbonyl groups, x, 81

carboxylic acids, 173

carcinogenesis, x, 46, 47, 53, 58, 67, 68, 77, 78

carcinogenicity, 84

carcinoma, viii, 6, 14, 15, 16, 78

cardiac output, 33

cardiomyopathy, 24

cardiovascular disease, vii, ix, xii, xiii, 22, 27, 35,

40, 43, 44, 45, 50, 51, 56, 76, 121, 122, 129, 130,

132, 133, 136, 137, 150, 151, 176, 179, 186, 188

cardiovascular morbidity, 130, 132

cardiovascular risk, 45

cardiovascular system, 33

carrier, 64, 161, 183, 184

catabolism, 92

catalysis, xi, 82, 99, 106, 107, 108, 113

catalyst, 108, 112

catalysts, 108, 109, 112, 113

catalytic activity, 13, 101, 117

catatonic, 25

catecholamines, 22, 31, 37, 142

causal relationship, 59, 178

causality, 136

CBS, 65

CD8+, 78

CE, 75, 79

196 Index

cell, v, vii, viii, 5, 6, 7, 10, 13, 14, 15, 16, 17, 18, 19,

29, 41, 51, 63, 65, 71, 74, 75, 78, 80, 93, 94, 101,

109, 155, 161, 181, 182

cell culture, 15

cell cycle, 7

cell death, 29

cell growth, vii, 7, 15, 16, 161

cell line, 14, 15, 18, 19

cell metabolism, vii

Central America, 23

central nervous system, ix, xiii, 29, 39, 175, 176

cerebrospinal fluid, 145, 147

cerebrovascular damage, 140

cerebrovascular disease, 67, 143, 146

cervical intraepithelial neoplasia, 47

cervix, viii, 6, 14, 15, 16, 47, 53, 67

chelates, 154, 157, 163, 170, 173

chemical properties, 109

chemical reactions, 129

chemical structures, 7

chemoprevention, 71

chemotherapy, 49, 56, 166

Chicago, 122

childhood, 177

children, xiii, 29, 32, 44, 48, 55, 58, 61, 62, 70, 73,

77, 132, 175, 176, 177, 186, 187

China, 49, 55, 153, 169, 170

Chinese, 169, 170, 171

chloride, 162, 163, 165

cholangiography, 169

cholesterol, ix, xiii, 22, 32, 33, 35, 82, 176, 186

chorea, 178, 187

chromatograms, 16

chromatography, 15, 16

chromosome, 17, 123

chronic diseases, 40

chronic renal failure, xii, 121, 132, 133, 136, 137

cigarette smoking, 29

circulation, 33, 64

classes, 7, 32

claudication, 33

cleavage, 97, 112, 114, 115

clinical presentation, 178

clinical symptoms, 60

clinical syndrome, 64, 70

clinical trials, 29, 40, 50, 132, 182, 183

cloning, 101

closure, 43, 115

clotting factors, 65

CO2, 14, 92, 167

coagulation, 75, 129

coagulation factor, 129

coagulation factors, 129

cobalamin, v, xi, xiii, 2, 3, 4, 65, 74, 81, 82, 87, 88,

91, 93, 94, 97, 143, 144, 147, 148, 149, 150, 151,

175, 176, 178, 179, 180, 181, 183, 185, 186, 187,

188, 190

cobalt, xiii, 89, 175, 176

cocaine, 30

coding, 96

coenzyme, viii, ix, xi, xii, 6, 21, 22, 23, 24, 31, 36,

94, 96, 97, 98, 99, 100, 102, 104, 107, 113, 117,

139, 140, 179

cognition, 3, 140, 144, 148, 151

cognitive dysfunction, 24

cognitive function, 4, 149, 150, 151, 152

cognitive impairment, 144, 145, 148, 149, 179

cognitive performance, 4, 149

cohort, 44, 79, 132, 187

colectomy, 74

colitis, 60, 62, 67, 68, 70, 78, 79

colon, x, 6, 16, 17, 18, 46, 47, 53, 54, 57, 58, 59, 62,

70, 78, 137

colon cancer, 6, 18, 46, 47, 53, 54, 70, 78, 137

colonoscopy, 79

colorectal cancer, 18, 50, 53, 64, 68, 69, 70, 71, 72,

77, 78, 79, 80, 132

coma, 25

combination therapy, 179

communication, v, 1, 3

community, 144, 145

competition, 94

complications, ix, x, 24, 39, 40, 48, 57, 58, 59, 61,

64, 65, 67, 70, 71, 72, 75, 76, 77, 79, 177, 186,

190

components, 49, 59, 65, 71, 155

compounds, v, viii, xi, xii, 5, 6, 7, 8, 9, 10, 11, 13,

14, 15, 81, 85, 86, 87, 88, 91, 92, 93, 94, 95, 96,

100, 150, 153, 154

concentration, 6, 10, 11, 12, 14, 61, 64, 73, 93, 126,

129, 134, 135, 143, 144, 145, 155, 156, 158, 161,

167, 177, 179, 191

conception, ix, 39

condensation, 122

confidence, 2

configuration, 83

conflict, 22

confusion, 140, 144

congress, 2

Congress, 170

Index 197

conjugation, 40, 100, 163

Connecticut, 37

consciousness, 144

consensus, 40, 188

conservation, 65, 119

consumption, ix, xiii, 21, 47, 50, 59, 176, 186, 191

contaminant, 84

contamination, 85

contrast agent, xiii, 153, 154, 155, 156, 157, 159,

160, 161, 162, 163, 164, 165, 168, 169, 170, 171,

172, 173, 174

control, x, 11, 14, 16, 35, 40, 46, 53, 61, 76, 78, 79,

91, 93, 100, 117, 131, 145, 159, 161, 166, 168,

177

control group, 131

controlled studies, 22, 68, 130

controlled trials, 46, 50, 53, 131, 188

conversion, viii, xi, xii, 6, 10, 15, 44, 81, 82, 83, 84,

86, 87, 90, 91, 92, 93, 94, 96, 101, 102, 107, 114,

115, 139, 140, 179

conviction, xii, 139, 146

copolymers, 173

coronary artery disease, 45, 51, 65, 76

coronary heart disease, 45, 52, 143

correlation, 61, 63, 66, 73, 93, 125, 157, 182

correlations, 4

cortical neurons, 146

corticosteroids, 60

costs, 3

coupling, 91, 92, 93

creatine, 124

creatinine, 124, 125, 126

Crohn’s disease, x, 57, 58, 59, 60, 61, 62, 63, 65, 67,

70, 72, 74, 75, 79

cross-sectional study, 47, 76

crude oil, 98

crystal structure, 102, 108

crystalline, 33

CSF, 150

culture, 14, 18, 91, 167

curing, 23

CVD, 44

cyanocobalamin, vii, 1, 2, 3, 4, 91, 146, 179, 184,

185

cyclooxygenase, 25

Cyclosporin, 125

cyclosporine, 125

cyst, 104

cystalysin, xi, 99, 100, 101, 102, 103, 104, 105, 106,

107, 108, 109, 110, 111, 112, 113, 114, 115, 116,

117, 118, 119

cystathionine, 44, 65, 104, 117, 122, 123, 124, 126,

132

cysteine residues, 96

cystine, 104, 143, 172

cystitis, 128

cytokines, 65, 75

cytotoxicity, 6, 19, 159, 162, 166

D

danger, 2

data analysis, 73, 130

database, 90

DD, 29

death, 24, 25, 26, 27, 30, 33, 44, 80, 137

death rate, 33

decay, 107

decisions, 184

defects, ix, xiii, 24, 39, 40, 43, 50, 51, 55, 68, 71, 77,

130, 175, 176, 181

deficiency, vii, ix, x, xii, xiii, 1, 2, 3, 4, 19, 22, 24,

26, 27, 29, 30, 35, 37, 39, 42, 43, 44, 46, 48, 49,

50, 52, 58, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70,

71, 72, 74, 75, 78, 79, 98, 122, 131, 137, 139,

140, 144, 145, 147, 148, 149, 150, 151, 175, 176,

177, 178, 179, 180, 181, 182, 183, 184, 185, 187,

188, 189, 191

deficit, 91, 149

definition, 176

degradation, v, xi, 81, 82, 83, 84, 85, 86, 87, 91, 92,

93, 94, 95, 96, 98

degradation pathway, v, 81, 84, 86, 87, 91, 93

degradation rate, 92

dehydration, 84

delirium, 144

delivery, 101, 166, 174

delusions, 144

demand, ix, 22

dementia, ix, 4, 22, 26, 39, 40, 43, 45, 46, 50, 140,

144, 145, 146, 147, 148, 149, 150, 151, 152, 178

demographic change, 183

demyelinating disease, 178

demyelination, 147, 178, 179, 187

dendrimers, 157, 163, 165, 173, 174

denitrifying, 87, 97, 98

density, 129

deoxyribonucleic acid, 19, 41

198 Index

depression, vii, 26, 27, 28, 40, 43, 46, 53, 140, 144,

145, 150, 179

derivatives, xii, 30, 32, 153, 154, 156, 173

dermatitis, 26

dermatology, 182

destruction, 181

detection, xiii, 105, 107, 147, 154, 159, 175, 176

detection techniques, 147

developed countries, 59

deviation, 177

DG, 52, 73, 76, 77, 78, 79, 148, 149, 169, 187

diabetes, 29, 185

diabetic patients, 124, 133

dialysis, xii, 121, 124, 126, 127, 129, 131, 132, 133,

134, 135

diarrhea, 26, 27

diet, viii, 18, 21, 23, 26, 41, 52, 58, 64, 70, 72, 73,

127, 130, 146, 177

dietary habits, 58

dietary intake, 6, 42, 43, 45, 47, 59, 62, 63, 181

differential diagnosis, 178

differentiation, 180, 183

diffusion, 33, 185

digestion, 59

dihydropteridine reductase, viii, 21, 24

dimer, 102

disability, 27

discomfort, 61, 184

disease activity, 66, 72, 73

disease progression, 101, 146

disorder, 26, 29, 82, 179, 180

displacement, xi, 100, 115, 121, 122, 128

dissociation, 107

distribution, 95, 166, 169, 171

division, vii

DNA, v, viii, xii, xiii, 5, 6, 7, 8, 9, 10, 11, 12, 13, 17,

19, 41, 46, 68, 69, 71, 78, 129, 132, 137, 139,

142, 143, 152, 167, 175, 176, 179, 180, 181

DNA damage, 68, 69, 152, 179

DNA polymerase, v, viii, 5, 6, 7, 8, 9, 10, 11, 12, 19

DNA repair, 7, 68, 71

DNA strand breaks, 68, 69

doctors, 34

donations, 17

dopachrome, ix, 22, 30, 31

dopamine, ix, 22, 30, 31, 32

dopaminergic, 145

dosage, 23, 47, 50, 163, 184, 185

dose-response relationship, 179

double-blind trial, 80

Down syndrome, 132

drinking water, 84

Drosophila, 190

drug carriers, 166

drug delivery, xiii, 153, 154, 166, 168, 173, 174

drug delivery systems, 166, 174

drug design, 169

drug release, 166, 173

drug use, 49

drugs, 7, 23, 25, 26, 27, 29, 31, 35, 40, 41, 43, 48,

60, 66, 124, 125, 128, 133, 144, 161, 166, 167,

168, 169, 174

DSM, 83

duration, 66, 68, 146, 155, 159, 163, 164, 178, 179,

182

dysplasia, 68, 70, 77, 78, 79

dystonia, 178, 187

E

E. coli, viii, 6, 9, 10

E.coli, 115

eating, ix, xiii, 21, 29, 42, 176, 186

eating disorders, 29

education, 2

EEG, 33

egg, 32

elderly, ix, 3, 4, 22, 32, 34, 35, 42, 48, 52, 73, 140,

144, 145, 147, 148, 149, 150, 151, 152, 183, 187,

188, 190, 191

elderly population, 52, 140, 148, 151

electron, 100, 182

embolism, 33

embolus, 33

employment, 84, 87, 94

enantiomers, xi, 99, 109, 112

encephalopathy, 36

encoding, 94, 98

endothelial cells, 17

endothelial dysfunction, 66

endothelium, xii, 44, 67, 75, 140, 143, 146

endotoxemia, 171

end-stage renal disease, 123, 124, 126, 128, 129,

131, 132, 133, 135, 136

energy, 27, 41, 58, 91, 92, 93, 111, 116, 177

England, 130

enthusiasm, 33

environment, 85, 93, 95, 100, 112

environmental factors, 59

Environmental Protection Agency, 95

Index 199

enzymatic activity, 23, 171

enzyme, viii, x, xi, xii, 6, 7, 9, 11, 21, 23, 24, 27, 29,

41, 44, 65, 69, 81, 82, 85, 88, 89, 94, 95, 97, 99,

100, 102, 105, 106, 107, 108, 109, 112, 113, 114,

115, 117, 118, 123, 139, 143, 184

enzymes, viii, ix, x, xi, 6, 7, 9, 10, 11, 17, 21, 22, 23,

24, 36, 44, 46, 65, 76, 77, 81, 82, 83, 88, 90, 92,

93, 94, 99, 100, 101, 102, 103, 107, 108, 112,

115, 117, 119, 124, 127

EPA, 84, 95

epidemic, 26

epidemiologic studies, 145

epidemiology, 129, 136

epigenetics, 78, 137

episodic memory, 150

epithelium, 17

EPR, 170

equilibrium, 103

equipment, 93

ERA, 183

erythema nodosum, 182, 189

erythrocytes, 101, 118, 180

Escherichia coli, 97, 98

esophagus, 67

ester(s), 86, 95, 97, 103, 161, 171

estradiol, 133

Estrogen, 125

ethanol, 27, 29, 36

ethylene, 157, 173

ethylene glycol, 157, 173

etiology, 63, 72, 185

Europe, 97, 184, 189

evidence, ix, xiii, 17, 29, 30, 32, 39, 40, 44, 45, 46,

47, 48, 50, 52, 53, 59, 64, 67, 68, 76, 77, 83, 84,

85, 98, 115, 136, 140, 146, 147, 148, 149, 150,

175, 176, 178, 179, 185

evolution, xi, 82, 85, 91, 93, 94, 95, 119

excitotoxicity, 147, 152, 179

excretion, 3, 43, 124, 155, 166

experimental autoimmune encephalomyelitis, 179,

187

exploitation, 95

exposure, 129, 177

extraction, 133

F

failure, xii, 3, 31, 121, 124, 131, 177, 178, 181

failure to thrive, 177

family, 28, 47, 54, 102, 112, 117

family history, 47, 54

family life, 28

fat, 59, 60

fatigue, 28

fatty acids, 19, 82, 95, 98

FDA, 154, 184

FDA approval, 154

fears, 48

feces, 26

federal government, 27

feet, 182

females, 29

fermentation, 94

fertility, 123, 182

fertilization, 49

fetal alcohol syndrome, 29

fibroblasts, 98

filtration, 124

first generation, 154

fish, viii, 5, 7

fistulas, 60, 70

flexibility, 91, 94

fluorescence, 102

folate, ix, x, xii, 3, 4, 18, 39, 40, 41, 42, 43, 44, 45,

46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 60, 61,

63, 64, 65, 66, 67, 68, 69, 70, 71, 73, 74, 75, 76,

77, 78, 80, 124, 125, 126, 129, 130, 131, 132,

134, 137, 139, 140, 143, 144, 145, 146, 147, 148,

149, 150, 151, 180, 183, 184, 190

folic acid, ix, x, 23, 31, 39, 40, 41, 42, 43, 44, 45, 46,

47, 48, 49, 50, 51, 52, 53, 54, 55, 58, 68, 73, 78,

79, 80, 122, 123, 124, 126, 129, 130, 133, 134,

136, 137, 145, 146, 148, 150, 180, 181, 187, 188,

189

food, ix, x, xiii, 21, 39, 40, 42, 47, 48, 62, 70, 130,

132, 148, 176, 178, 181, 185, 191

food products, 40, 176

Ford, 117

fractures, ix, 39, 183, 190

fragility, 183

fragmentation, 167

Framingham study, 151

France, 155, 170

frontal lobe, 144

fruits, 50

fuel, xi, 81, 84, 85, 94, 95, 97

200 Index

G

gadolinium, 154, 155, 157, 158, 162, 163, 165, 169,

170, 171, 172

gangrene, 67

gasoline, 96, 97

gastric mucosa, 181

gastrin, 3, 4

gastritis, 3, 180

gastrointestinal tract, x, 57, 58, 67, 181

gel, 14

gender, 42, 45, 123

gene, viii, 17, 19, 21, 23, 35, 43, 46, 68, 69, 76, 94,

98, 101, 123, 187

gene expression, 17, 19, 68, 69

generalization, 23

generation, xiii, 92, 141, 176, 186

genes, 17, 59, 69, 96

genetic defect, 43, 44, 65

genetic disease, 23, 24, 36

genetic disorders, viii, 21, 24, 44

genetic factors, 50, 59

genetic mutations, 24, 123

genetics, 43, 78

genome, 100

genome sequencing, 100

genotype, x, 40, 45, 46, 47

Germany, 81, 155, 156, 169

gestation, 55

gingival, 101

glass, 95

glomerulonephritis, 33

glucagon, 123

glucocorticoids, 123

glucose, 24, 127

glutamate, 143

glutamic acid, 40, 172

glutamine, 55

glutathione, 37, 77, 116, 119

glutathione peroxidase, 37

glycerol, 157

glycine, 98, 105, 106, 143

glycogen, 19

glycol, 173

goals, 182

gold, 33, 130

government, 43

grains, 42

Greece, 57

ground water, 96

groundwater, 84, 85

group work, 2

groups, vii, x, xiii, 1, 43, 48, 58, 61, 70, 87, 89, 129,

130, 153, 154, 156, 157, 160, 162, 163, 164, 165,

169, 171, 186, 187

growth, viii, 6, 14, 15, 18, 19, 58, 83, 91, 92, 93, 97,

98, 101, 116, 119, 159, 166, 167, 177

growth factor, 6

growth rate, 91, 92, 93

guidelines, 4, 132, 176, 188

gut, 59, 62, 77

H

hallucinations, 144

hands, 182

harm, 7, 45, 130, 132

harmony, 7

harvesting, 42

Hawaii, 147, 170

Hcy, ix, 39, 44, 45, 46, 179, 183

HD, 78, 128

HDL, 33

HE, 73

health, vii, ix, x, xiii, 2, 22, 24, 25, 26, 27, 35, 39,

40, 43, 49, 51, 52, 95, 148, 150, 176, 177, 183,

186, 191

health care, 2

health effects, 95, 186

health problems, vii, xiii, 24, 49, 176, 177, 186

Heart, 37, 44, 137, 188

heart disease, 23, 44, 45, 187

heart failure, 29, 31, 37

heat, 42

helicobacter pylori, 181

Helicobacter pylori, 188

hematology, 74

hemodialysis, xii, 122, 126, 128, 129, 131, 133, 134,

135, 136, 137

hemoglobin, 2, 101

hemolytic anemia, 24

hemostasis, 75

hepatobiliary system, 156, 171

hepatocytes, xiii, 153, 154, 156

hepatoma, 18, 19

hepatotoxicity, 55

heroin, 30

herpes simplex, 6

heterotrophic, 92

hexane, 98

Index 201

HHS, 46, 53

higher education, 186

high-performance liquid chromatography, 97

hip, 50, 183, 190

hip fractures, 190

Hippocrates, 132

histology, 63

HIV, viii, 6, 9, 10

homeostasis, xiii, 175, 176

homocysteine, ix, xi, xii, 2, 3, 4, 39, 41, 43, 44, 45,

49, 51, 52, 63, 65, 66, 67, 71, 73, 76, 77, 79, 80,

121, 122, 123, 124, 125, 126, 127, 128, 129, 130,

131, 132, 133, 134, 135, 136, 137, 139, 140, 142,

143, 144, 145, 146, 147, 148, 149, 150, 151, 152,

179, 183, 184, 186, 188

Honda, 190

Hong Kong, 27, 36

hormone, 28, 124, 125, 177

hospitalization, 136

hospitals, 24, 25, 26, 32, 154

House, 134, 135

human umbilical vein endothelial cell, viii, 6, 13

Hungary, 74

HUVEC, viii, 6, 13, 14, 17

hydrocarbons, 84, 96

hydrogen, 89, 90, 100, 102, 103, 106, 107, 109, 111,

112, 118, 154

hydrogen abstraction, 106, 107, 112

hydrogen bonds, 102

hydrogenation, 157

hydrolysis, 41, 112, 143, 166

hydrophobic, 112

hydroxyl, 7, 90, 103, 184

hypercholesterolemia, 32

hyperhomocysteinemia, xii, 45, 50, 53, 56, 64, 65,

66, 67, 71, 72, 76, 77, 121, 122, 124, 126, 131,

133, 134, 135, 136, 145, 146, 179

hyperpharylalaninemia, viii, 21

hyperplastic polyps, 54

hypersensitivity, 40, 48, 49, 152

hypertension, 23, 29

hyperthyroidism, 124

hypoglycemia, 24

hypohomocysteinemia, xii, 121

hypomethylation, 69, 129

hypotension, 183

hypothesis, xiii, 26, 30, 31, 33, 84, 100, 112, 113,

124, 129, 131, 175, 176

hypothyroidism, xi, 121, 124, 133, 140

hypotonia, 177

hypoxia, 33

I

iatrogenic, x, 57, 59

IBD, x, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 70,

71, 72

ICM, x, 81, 82, 83, 84, 85, 88, 89, 90, 93, 94

identification, 106

IFN, 179, 187

ileostomy, 63, 73, 74

ileum, 62, 64, 73, 181

images, 155, 157, 159, 160, 163, 164, 165

imaging, 154, 156, 157, 162, 163, 165, 169, 170,

171, 172, 174

imbalances, ix, 22, 31, 91

immigrants, 43

immunity, 182

immunomodulatory, xiii, 175, 176, 178

immunosuppressive agent, x, 57

implementation, 144

in situ, 84

in vitro, 6, 13, 17, 18, 19, 55, 68, 132, 161, 166, 172,

173, 184

in vivo, viii, 6, 7, 10, 15, 19, 155, 166, 169, 174,

179, 184

incidence, 23, 37, 43, 44, 54, 59, 65, 68, 74, 78, 79,

145, 146, 151, 183

inclusion, 130

India, 147, 185, 187, 190

indicators, 183

infants, 55, 177

infarction, 34, 75

infertility, 23, 189

inflammation, xii, 34, 60, 63, 67, 73, 121, 130, 136,

137, 183, 190

inflammatory bowel disease, x, 49, 58, 59, 60, 61,

64, 65, 67, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79

inflammatory response, 183, 190

ingestion, 181

inhibition, viii, xii, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16,

17, 18, 63, 139, 143, 146

inhibitor, viii, 5, 6, 8, 10, 17, 19, 115, 129, 143, 181

inhibitory effect, viii, 5, 10, 11, 12, 13, 14, 17

initial state, 89

injections, 2, 31, 34, 164, 182, 184

injury, 59, 67

inmates, 26, 27

insects, viii, 6, 7

insight, 112, 119

202 Index

instability, 80

instruments, 144

insulin, 123

integrity, 68

intelligence, 3, 190

intensity, 102, 155, 159, 162

interaction, 11, 46, 48, 50, 59, 105, 106, 107, 109,

113, 118, 172, 173

interactions, 40, 43, 48, 69, 100, 102, 113, 170

interferon, 190

interpretation, 30, 51

intervention, ix, 4, 22, 45, 47, 49, 130, 137, 144, 146

intestine, 166, 185

intima, 32, 67, 77

intramuscular injection, 71, 184

intravenously, 30, 33

iodine, 16

ionization, 103, 107

ions, 117, 162

IR, 149, 188

Ireland, 39

iron, 2, 74, 101, 180, 188

irritability, 177

ischaemic heart disease, 52, 67

ischemic stroke, 80, 137, 179, 183

ischemic stroke risk, 179

isobutyryl-CoA, x, 81, 82, 83, 89, 90, 96, 97, 98

isolation, 97

isomerization, 83, 87, 96

isotope, 133

Israel, 175, 185

Italy, 99, 121, 129, 139, 155

J

Japan, 5, 14, 15, 17, 18, 184

job performance, 28

Jordan, 191

K

keratinocytes, 182

kidney, xii, 43, 121, 136, 155, 166, 174

kidneys, 42, 166

kinase, 125

kinetic constants, 93

kinetic parameters, 107, 110, 113, 115

kinetic studies, 2, 118

kinetics, 2, 80

L

labeling, 83, 88

labour, 95

lactation, 42, 177

language, 144

leakage, 127

learning, 34

Leigh disease, 24

lens, xi, 121, 122

leptin, 177, 187

lesions, 46, 145, 182

leukemia, 67

leukopenia, 180

life expectancy, 23

life style, xiii, 176, 186

lifestyle, 59

ligand, 107, 115, 156, 158

ligands, 113, 154, 156, 157, 161, 162, 165

likelihood, 43, 145

linkage, 100, 102

links, 24

lipids, 134

literature, ix, 22, 23, 25, 30, 35, 70, 140, 188

liver, xiii, 17, 19, 27, 35, 41, 42, 64, 132, 153, 154,

155, 156, 157, 159, 160, 161, 162, 163, 165, 166,

168, 169, 171, 184

liver cancer, 169

liver cells, 159, 166

liver disease, 184

liver enzymes, 35

longevity, 33

longitudinal study, 27

LSD, 30, 31, 35

lung, 6, 16, 18, 166

lung cancer, 16, 18

lupus, 49

lycopene, 137

lymphoma, 184

lysine, 100, 107, 108, 118

M

macrocytosis, 180

macromolecules, xiii, 153, 154, 166

macronutrients, 59

macular degeneration, 23

magnetic field, 154

Index 203

magnetic resonance, xiii, 153, 154, 169, 170, 171,

172, 173

magnetic resonance imaging, xiii, 153, 154, 169,

170, 171, 172, 173

maize, ix, 21, 22, 26, 35

malabsorption, x, 2, 3, 4, 42, 57, 60, 62, 63, 66, 73,

144, 181, 185, 188, 189

male infertility, 189

malignant cells, 169

malignant melanoma, 18

malnutrition, x, xii, 27, 57, 58, 59, 61, 64, 66, 71,

121, 129, 136

mammalian cells, 7

mammography, 54

management, x, 57, 58, 59, 63, 70, 71, 72, 189

manganese, 171

mania, 179

manic, 144

marrow, 189

Maryland, 36

masking, 48, 181

maturation, 2

meals, 26

measurement, 74, 172, 184

meat, xiii, 26, 176, 185, 191

media, 67, 77, 159, 186

median, 178

medication, 28, 34

medicine, 2, 22, 23, 132, 150, 151, 154, 185

Medline, 53, 78

megaloblastica, ix, 39

melamine, 174

melanin, 182

melanoma, 18

membranes, 127, 181

memory, 28, 34, 144, 145, 149, 150

memory performance, 150

men, 18, 33, 45, 47, 48, 53, 54, 147, 151, 183

menopause, 123

mental disorder, 27, 40, 45, 50, 151

mental health, 150

mental illness, 25, 28, 29

meta-analysis, 50, 52, 53, 68, 77, 79, 129, 130, 136,

188

metabolism, vii, xii, 2, 4, 6, 27, 44, 46, 49, 51, 62,

63, 65, 66, 68, 69, 70, 73, 76, 77, 78, 82, 83, 84,

85, 91, 92, 93, 94, 95, 97, 116, 119, 122, 124,

125, 126, 127, 132, 133, 134, 139, 140, 141, 143,

150, 161, 177, 181, 183, 184, 188

metabolites, 30, 37, 91, 92, 93, 100

metabolizing, 77

metal ions, 154

metastasis, 16

metformin, 181, 188

methane, 98

methanol, 15, 16

methionine, xii, 41, 44, 46, 47, 53, 54, 65, 67, 69, 70,

105, 106, 107, 122, 124, 126, 130, 131, 133, 137,

139, 140, 141, 142, 143, 179

methionine synthetase, xii, 139, 143

Methotrexate, 49, 56, 61, 124, 125

methyl group, 41, 65, 123, 131, 140, 143

methyl tertiary, 95

methylation, xii, 41, 53, 68, 69, 78, 131, 136, 137,

139, 140, 142, 143, 146, 147, 150

methylene, 41, 43, 44, 76, 123

methylmalonyl-CoA, x, 81, 82, 83, 88, 89, 96, 97,

98, 179

Mexico, 185

mice, 6, 16, 17, 18, 36, 78, 145, 157, 162, 166, 179

Microbial, 95, 96

microcirculation, 65

microenvironment, 59

micrograms, 2, 30, 42, 43, 46, 184

micronutrients, 59, 69, 71, 137

microorganism(s), 84, 85, 91, 92, 95

microscope, 14

middle class, 186

migraine, 183, 190

milk, 26

Millennium, 170

milligrams, 26, 30, 34, 185

minerals, 28, 62

Ministry of Education, 18

Minnesota, 33

Mississippi, 26

mitochondria, 82

mitotic, 25

MMA, 177, 184

mobility, 17

modeling, 112

models, 180

modern society, 186

moieties, 86, 90, 96, 171

molasses, 26

mole, 163, 166

molecular weight, xiii, 127, 153, 154, 156, 173

molecules, xiii, 102, 113, 122, 129, 153, 154, 155,

156, 168, 171

monograph, 34

204 Index

monomer, 102, 157

mood, 28, 150, 178

mood disorder, 28

morbidity, xi, 49, 67, 121, 129, 137

mortality, xi, 18, 37, 44, 49, 51, 67, 121, 124, 129,

130, 132, 136, 137, 151, 179, 183

mortality rate, 124, 129, 183

mortality risk, 137

mothers, 43, 177, 186

motivation, 145

motives, xiii, 176, 186

motor function, 179

mouse model, 78, 179

movement, 3, 4

MRI, xiii, 80, 152, 153, 154, 155, 156, 157, 159,

160, 161, 162, 163, 164, 168, 169, 170, 171, 172,

173, 174, 177, 178

mRNA, 19

mucosa, 67, 71, 77, 80, 182

mucous membrane, xiii, 175, 176

mucous membranes, xiii, 175, 176

multidimensional, 70

multiple myeloma, 184

multiple sclerosis, ix, 22, 30, 31, 35, 36, 37, 178,

187, 188

muscle weakness, 178

muscles, 33

mutagenesis, 69, 103, 107, 108, 112, 118, 119

mutant, 107, 112, 118

mutases, v, x, xi, 81, 82, 84, 87, 89, 90, 94

mutation(s), viii, 21, 23, 24, 49, 65, 68, 69, 76, 93,

107, 113, 115, 119

Mycobacterium, 87, 95, 97

myelin, 178

myeloproliferative disorders, 184

myocardial infarction, 80, 137, 188

myocardial ischemia, 172

myocardium, 33

myoclonus, 178

N

Na+

, 117

NAD, 29

National Research Council, 34

natural food, 50

natural gas, 88

nausea, 26, 60

necrosis, 75, 183

neocortex, 45, 52, 145, 151

neoplasia, 68, 69, 70, 71, 77, 78

Nepal, 55

nephritis, 33

nerve, 33, 48, 178

nerve cells, 33

nerve fibers, 178

nervous system, vii, xii, 48, 139, 140, 147, 150, 187

Netherlands, 191

network, 2

neuroblastoma, 67

neurodegeneration, 29, 36, 145, 179

neurodegenerative disorders, 146, 150

neurological disease, 147

neurological disorder, 30

neurons, 30, 34, 143, 152

neuropathy, 24, 79, 147, 176

neuropsychiatry, 52, 150

neuropsychological assessment, 149

neurotoxic effect, 140, 146

neurotoxicity, 143

neurotoxins, ix, 22

neurotransmitters, 142

neutrophils, 180

New England, 131

New York, 36, 52, 56, 150, 151

New Zealand, 50

next generation, 170

niacin, viii, ix, x, 21, 22, 23, 24, 25, 26, 27, 28, 29,

30, 31, 32, 33, 34, 35, 36, 37, 51, 54, 58, 60, 61,

62, 134

niacin deficiency, viii, ix, 21, 22, 26, 29, 35

niacinamide, 22, 25, 29, 31, 34, 37

nicotinamide, 23, 26, 28, 29, 33, 37

nicotine, ix, 22, 29, 36

nicotinic acid, 22, 27, 28, 33, 36, 37, 58, 70

nitric oxide, 18, 128, 183, 184, 190

nitric oxide synthase, 18, 128

nitrification, 95

nitrilase, 85

nitrilase activity, 85

nitrogen, 60, 109, 111

NMDA receptors, 143

NMR, 154, 158, 170, 172

Nobel Prize, 122, 154

non-steroidal anti-inflammatory drugs, 182

normal development, xiii, 175, 176

North America, 24, 56

North Carolina, 97

Northern Ireland, 132

nuclear magnetic resonance, 154, 170

Index 205

nucleic acid, xii, 139, 141, 143, 146

nucleic acid synthesis, xii, 139, 141, 143, 146

nucleotides, 13

nutrients, ix, 18, 22, 23, 29, 32, 51, 53, 58, 60, 62,

66, 70, 78, 177

nutrition, 37, 42, 50, 101, 116

nutritional deficiencies, 59, 60, 62

nuts, 42

O

obesity, 181

observations, 17, 34, 47, 146, 178

obstruction, 44

occlusion, 67

oil, 36

old age, 34, 146, 149, 151

older people, 4

oligozoospermia, 189

organ, 31, 33, 154, 155, 157, 166

organic compounds, 94

organization, 89, 91, 94

orientation, 89, 100, 112

orthostatic hypotension, 178

osmolality, 155, 156

osteoarthritis, 34, 37

osteoporosis, xi, 40, 43, 50, 121, 122, 183, 190

outpatients, 147

ovarian cancer, 47, 54

overweight, 186

oxaloacetate decarboxylase, 119

oxidation, 25, 27, 30, 31, 41, 83, 84, 87, 98, 101, 143

oxidation products, 30

oxidative stress, ix, xii, 22, 30, 31, 32, 34, 37, 139,

143, 179

oxygen, 33, 42, 94, 109, 111

P

Pacific, 27

pain, 60, 61, 182

pancreas, 67, 156

pancreatic cancer, 47, 54

pantothenic acid, x, 51, 54, 58, 60, 134

paradigm shift, 23

parameter, 140, 147

parenchyma, 155

paresthesias, 178, 182

Paris, 151

parkinsonism, 30, 31, 178, 187

Parkinson's disease, ix, 22, 30, 31, 35, 36, 37, 124,

133, 145, 150

pathogenesis, x, 37, 57, 58, 59, 65, 72, 74, 78, 132,

182

pathogens, 101

pathology, xiii, 132, 140, 146, 175, 176, 178, 186

pathophysiology, 154

pathways, xi, xii, 65, 66, 77, 81, 84, 85, 86, 91, 92,

100, 125, 139, 140, 146

PCR, 26

pediatric patients, 67

pellagra, ix, 22, 23, 25, 26, 27, 28, 29, 33, 35, 36, 64,

70

performance, 145

perfusion, 172

periodontal, 23, 101

periodontal disease, 23, 101

periodontitis, 101

peripheral nervous system, x, 40

peripheral neuropathy, 145, 178

peripheral vascular disease, 143

permeability, 155

pernicious anemia, 2, 3, 4, 180, 185, 188

personal, 2, 131

personal communication, 2

pH, 62, 102, 103, 104, 106, 107, 109, 110, 114, 163

pharmaceuticals, 154

pharmacology, iv

phenol, 89, 102

phenotype, 74

phenylalanine, 113

phenylketonuria, viii, 21, 24

phenytoin, 43, 48

phosphate, viii, xi, 5, 6, 7, 8, 9, 10, 15, 18, 19, 24,

99, 100, 101, 102, 103, 104, 106, 107, 110, 114,

117, 118, 119, 156, 169

phospholipids, 141, 142

phosphorus, 109, 111

phosphorylation, 16, 92

photophobia, 70

physical exercise, 186

physical health, 154

Physicians, 36

physiology, 154

pilot study, 37, 149, 190

placebo, 4, 34, 68, 80, 128, 130, 146, 182

plants, viii, 6, 7, 85

plasma, xi, 4, 41, 43, 44, 45, 52, 62, 66, 67, 73, 75,

79, 117, 121, 122, 123, 124, 125, 126, 127, 128,

206 Index

129, 130, 131, 133, 134, 135, 136, 143, 144, 145,

146, 150, 151, 161, 179, 185

plasma levels, 62, 66, 73

plasma membrane, 117

plasticity, 150

platelet aggregation, 44

PLP, viii, xi, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,

17, 99, 100, 101, 102, 103, 107, 108, 110, 111,

112, 114, 115, 116, 117

PM, viii, 4, 5, 6, 7, 8, 9, 13, 14, 15, 51, 52, 53, 75,

76, 79, 147, 148, 151, 152, 157, 158, 159, 160,

161, 162, 163, 164, 165, 166, 167, 168, 186, 188,

190

PMMA, 135

poison, 25

pollutants, xi, 81, 91

poly(methyl methacrylate), 95

polycondensation, 157

polydispersity, 163

polyesters, 157, 158

polyether, 83, 95

polyethylene, 173

polymer, 161, 163, 166, 172, 173

polymerase, viii, 6, 9, 10, 19

polymerization, 157

polymers, 166, 167, 174

polymorphism(s), xi, 23, 24, 35, 36, 46, 69, 76, 79,

121

polypeptide, 88, 102

pools, 93

poor, 3, 26, 27, 31, 35, 43, 58, 59, 107, 112, 136

population, xi, xiii, 28, 47, 48, 51, 54, 55, 63, 64, 65,

68, 71, 72, 79, 121, 129, 130, 131, 132, 145, 149,

150, 151, 175, 180, 183, 185, 188, 191

pork, 26

portal vein, 67

positive correlation, 124

positive relation, 124, 145

positive relationship, 124, 145

postmenopausal women, ix, 39, 47, 54, 133

potassium, 104, 106, 110, 114

poverty, xiii, 176, 186

power, xi, 99, 100, 127

predictors, 76, 133

pregnancy, ix, 39, 40, 42, 43, 51, 53, 55, 177, 184

pressure, 33, 127, 135

prevention, 4, 22, 23, 26, 40, 43, 50, 51, 52, 56, 67,

68, 80, 130, 133, 136, 137, 146, 180, 181, 183,

184

primary biliary cirrhosis, 49

prisoners, 27, 35

prisons, 26

probability, 180

probands, 2

probe, 112

probiotic, 62

problem solving, 144

prodrugs, 86

production, 15, 41, 49, 83, 84, 86, 92, 93, 95, 96,

101, 113, 115, 116, 128, 181

prognosis, 31

program, 77, 130

prokaryotic pols, viii, 6, 10

proliferation, viii, 5, 6, 7, 13, 14, 15, 17, 18, 19, 68,

69, 180, 181, 183

promote, 29, 46, 53

propane, 97, 103

prophylactic, 72, 183

prophylaxis, vii, 1, 71, 183, 190

prostaglandin, viii, 21, 25, 36

prostaglandins, 25

protective role, 72

protein, viii, xi, xii, 11, 18, 21, 26, 58, 60, 65, 75, 93,

99, 101, 102, 108, 113, 118, 122, 124, 126, 128,

129, 135, 141, 143, 161

protein binding, 126

protein function, 129

protein synthesis, 141

proteins, 64, 100, 115, 117, 127, 129, 133, 141, 181,

183

proteinuria, 181, 189

prothrombin, 65

protocol, 31

protocols, 124

proton pump inhibitors, 181, 189

protons, 154

psoriasis, 49, 124

psychiatric disorders, 46

psychiatric illness, 179

psychiatric patients, 32

psychoses, 178

psychosis, 187

psychotic states, 144

psychotic symptoms, 179

public health, 48, 51, 53, 54, 130

pulmonary circulation, 67

pulmonary embolism, 67, 77, 80

pulse, 56, 127, 135

PUMA, 36

purines, 41, 141

Index 207

pyridoxal, viii, xii, 5, 6, 7, 9, 18, 19, 31, 100, 101,

117, 118, 119, 125, 153, 154, 156

pyridoxamine, viii, xii, 5, 6, 7, 9, 153, 154, 157, 159,

162, 163, 165, 166, 167, 170

pyridoxine, viii, x, xiii, 5, 6, 7, 9, 31, 58, 60, 146,

153, 154, 156, 168

pyrimidine, 13, 17, 68

pyrophosphate, 117

Q

quartile, 145

R

racemization, xi, 99, 100, 108, 109, 110, 111, 112,

115, 119

randomized controlled clinical trials, 131

range, ix, 17, 22, 23, 29, 30, 35, 46, 102, 130, 161,

184

rare earth elements, 84

Raynaud's disease, 33

reactants, 73

reaction center, 90

reaction mechanism, 89, 108, 110

reaction rate, 29

reality, 27, 30, 180

receptor sites, ix, 22, 29

receptors, viii, xii, 21, 22, 25, 129, 140, 143, 146,

147, 181

recombination, 7

reconstruction, 181

recovery, 33, 36, 149, 182

rectum, 53, 78

recurrence, 182

red blood cell(s), vii, 64, 68, 101

red meat, xiii, 176, 186

reduction, 40, 45, 50, 52, 93, 107, 113, 123, 126,

128, 129, 130, 134, 135, 141, 180, 181, 182

reflexes, 178

refractory, x, 57, 58

regenerate, 112

regeneration, 171

regional, 33

Registry, 136

regression, 47

regulation, xiii, 132, 175, 176, 177, 186

relapses, 2

relationship, ix, xii, xiii, 31, 39, 45, 47, 50, 51, 66,

68, 117, 121, 122, 129, 144, 146, 148, 176, 177,

179, 183, 186

relaxation, 154, 156, 157, 158, 162, 170

relaxation effect, 157, 158, 162

relaxation rate, 154

relevance, 36, 146, 179

reliability, vii, 1

remethylation, xii, 44, 65, 121, 122, 124, 125, 126,

127, 131, 133, 139, 143

remission, 59, 62, 72, 73, 182

remyelination, 187

renal failure, xi, 121, 123, 125, 135

renal function, 123, 124, 129, 132, 133

repair, 7, 10, 17, 32, 46, 187

replication, 7, 17, 19, 41, 91

resection, 60, 62, 63, 64, 70, 71, 73, 74

residues, xi, 40, 89, 90, 100, 102, 106, 108, 112, 155

resistance, 75, 185

resolution, 100, 118, 183, 190

resources, 84

responsiveness, 53

retardation, 177, 178

retention, 83, 157, 165

retina, 33

reverse transcriptase, viii, 6, 9, 10

RF, 52, 56, 149

rheumatoid arthritis, 34, 49, 56, 124, 133

riboflavin, x, 23, 31, 51, 54, 58, 60, 61, 65, 69, 70,

79, 134

rice, 26, 27

rickets, 23

risk, viii, ix, x, xii, 6, 16, 18, 21, 24, 28, 29, 39, 40,

42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54,

59, 62, 64, 65, 66, 68, 70, 71, 72, 73, 76, 77, 78,

79, 121, 123, 124, 126, 127, 129, 130, 131, 132,

134, 136, 137, 145, 146, 150, 151, 177, 179, 183,

186, 187, 188, 190

risk factors, 45, 59, 68, 132, 145, 183

RNA, viii, 6, 9, 10, 19

room temperature, 157

Rouleau, 31, 37

S

SA, 11, 53, 78, 148, 150, 155

safety, vii, 1, 40, 48, 50, 183, 185

salmon, 7, 9

salt, 98

salts, 91

208 Index

sample, 32, 145, 186

Schilling test, 2, 63, 64

schizophrenia, 22, 24, 25, 26, 31, 32, 34, 35, 36

Schizophrenia, 25, 36

schizophrenic patients, 24, 34

school, 33

science, 23, 77

sclerosis, 179

scores, 144

search, 185

Second World, 27

secretion, 181

seizure(s), x, 26, 40, 48, 178, 187

selenium, 31, 137

sensation, 178

sensitivity, 176, 184

separation, 97

sepsis, 183, 190

septic shock, 31, 37

sequencing, 94, 97, 98

series, xii, 24, 27, 30, 52, 63, 65, 153, 154, 156, 163

serine, 104, 105, 106, 122, 141

serum, x, xii, xiii, 2, 3, 4, 11, 18, 24, 45, 48, 50, 52,

54, 58, 60, 61, 62, 63, 64, 66, 67, 71, 75, 124,

125, 129, 133, 139, 140, 144, 145, 146, 149, 151,

152, 159, 175, 176, 177, 179, 181, 182, 183, 184,

186, 187, 189, 191

serum albumin, 11, 124, 129

severity, 23, 30, 34, 45, 52, 61, 62, 145, 151, 179,

181, 182

sex, 123

shock, 31, 55, 183, 190

sibling, 29

siblings, 189

side effects, 30, 35, 36, 49, 126, 132, 184

sign, 2, 32, 182

signals, 154, 165

signs, xi, 75, 121, 176, 178, 179, 189

similarity, 7

sites, 12, 29, 30, 40, 43, 46, 67, 85, 128, 129

skeletal muscle, 19

skeleton, 88, 96, 98

skills, 144

skin, vii, xiii, 25, 175, 176, 189

small intestine, 62, 74, 166

smokers, 47, 53

smoking, 22, 186

smooth muscle cells, 44

social status, 185

society, 183, 186, 188

sodium, 119

software, 109

soil, xi, 82

South America, 185

South Korea, 2

spastic, 33

spasticity, 178

species, 7, 10, 83, 102, 105, 107

specificity, xi, 82, 90, 91, 93, 94, 99, 100, 104, 109,

117, 119, 155, 184

spectroscopy, 105

spectrum, x, 36, 81, 83

speculation, 17

speed, 92

spina bifida, 43, 51, 177, 186

spinal cord, 67, 77, 155

spinal cord injury, 67, 77

spine, 43

spleen, 162, 166

spore, 96

stability, 68, 69, 78, 146, 156, 161

stabilization, 28

stages, 28, 46

stasis, 63

stereospecificity, 83, 96

steroids, x, 57, 58

stomach, 25, 67

stomatitis, xiii, 175, 176, 182, 189

storage, viii, ix, 21, 42, 177

strain, 93, 95

strategies, 50, 96, 117, 144, 183

strength, 96, 143

Streptomyces, x, 81, 82, 83, 94, 97, 98

stress, vii, xiii, 22, 24, 32, 33, 76, 175, 176

strictures, 60

stroke, ix, 4, 22, 33, 34, 35, 67, 77, 80, 127, 130,

137, 145, 151, 183, 187, 188, 190

stroke volume, 33

structural gene, 91

subacute, 144, 145

subgroups, xii, 58, 122, 130

subsidy, 18

substitution, 29

substrates, xi, 7, 81, 83, 89, 90, 92, 93, 104, 105,

106, 107, 112

suffering, x, 26, 28, 30, 32, 57, 58, 177, 182, 183

sugar, 28, 59

sulfate, 62, 83, 87, 94, 95, 96

Sulfide, 62

sulfonamides, 41

Index 209

sulfur, xii, 65, 77, 104, 122, 139, 143

sulphur, 122

Sun, 118

superoxide, 37, 129

supply, ix, 21, 41, 77, 92, 93, 148

suppression, 17, 182

surface chemistry, 163

surfactants, 173

surveillance, 77, 79

survival, xii, 19, 31, 49, 55, 122, 190

survival rate, xii, 122

susceptibility, 59, 78, 123, 137, 154

susceptibility genes, 59

Sweden, vii, 1, 2, 3, 55, 190

symptom(s), vii, ix, 22, 24, 25, 26, 28, 30, 34, 40,

48, 64, 140, 144, 146, 149, 151, 176, 178, 179,

181, 189

syndrome, xii, 29, 70, 121, 179, 181, 183, 185, 187,

189, 190

synovial fluid, 95

synthesis, viii, xiii, 7, 21, 25, 41, 46, 65, 67, 68, 69,

82, 83, 84, 91, 92, 93, 94, 109, 117, 140, 141,

143, 169, 170, 171, 172, 173, 175, 176, 178, 180,

181, 182

systemic circulation, 67

systems, xiii, 59, 85, 94, 161, 166, 175, 176

T

T cell, 78

tacrolimus, 125

Taiwan, 170

targets, 7, 19, 41

TCC, 82, 92

teeth, 32

temperature, 172

temporal lobe, 45, 146

Texas, 55

textbooks, 180

theory, 23, 44, 92, 127, 130, 170

therapeutic goal, 182

therapy, vii, x, xii, 1, 2, 3, 4, 30, 34, 35, 36, 37, 48,

56, 57, 58, 75, 77, 121, 122, 124, 125, 126, 128,

129, 130, 131, 132, 133, 134, 144, 146, 147, 148,

149, 174, 178, 182, 183, 184, 188, 189

thiamin, 31, 51, 54, 60, 62

thinking, ix, 39, 40, 127

threshold level, 179

threshold(s), 93, 179

thrombocytopenia, 180

thromboembolism, 76

thrombosis, 44, 62, 64, 65, 66, 67, 70, 71, 73, 75, 76,

77, 80, 131, 137

thyroid, 124

time, ix, xii, 2, 3, 25, 26, 27, 30, 32, 33, 34, 39, 43,

47, 55, 73, 92, 113, 114, 122, 127, 129, 131, 146,

157, 159, 165, 166, 181, 182

timing, 47, 50, 71

tissue, 26, 59, 64, 154, 155, 166, 171

tobacco, 29, 30, 35

Tokyo, 17, 118

topoisomerases, viii, 5, 7, 9, 19

topology, 100

topos, viii, 5, 7, 10, 17

total parenteral nutrition, 79

total plasma, xi, 46, 121, 123, 125, 126, 127, 128,

129, 130, 131, 132, 136

toxic effect, xii, 43, 49, 128, 129, 140, 143, 146

toxic side effect, 49, 166, 169, 180

toxicity, 25, 40, 48, 55, 56, 124, 135, 143, 155, 162,

166, 169

toxin, 62

trade, 92

trade-off, 92

tradition, 2

transduction, 92

transfer RNA, 24

transgenic, 179

transition, 115

translation, 7

transmission, 152

transplantation, 123, 132, 133

transport, xiii, 128, 143, 153, 154, 181, 182

trauma, 183

Treponema denticola, xi, 99, 116, 117, 118, 119

trial, xii, 4, 28, 36, 45, 47, 48, 52, 54, 71, 80, 122,

126, 128, 130, 134, 136, 137, 187, 190

tricarboxylic acid, 82

triggers, 77, 140

triglycerides, 33

trisomy 21, 123

trypsin, 14

tumor, 6, 16, 17, 18, 46, 69, 75, 167, 168, 184

tumor cells, 167, 168, 184

tumor growth, 6, 16, 18, 46, 184

tumor necrosis factor, 75

tumorigenesis, 16, 18

tumors, 46, 53, 169

turnover, xi, 63, 64, 83, 94, 100, 110, 113, 116, 177,

181, 183, 190

210 Index

twinning, 40, 48, 49, 55

twins, 55

tyrosine, 113, 118

U

ulcer, 182

ulcerative colitis, x, 57, 58, 59, 63, 64, 65, 67, 68,

71, 72, 73, 74, 75, 76, 77, 78, 79, 80

ultrasound, 183, 190

ultraviolet light, 32

uncertainty, 48

uniform, 163

United States, 18, 23, 26, 35, 36, 96, 98, 137

unplanned pregnancies, 43

urine, vii, 31, 32, 37, 122, 184

UV, 105

V

validity, 25, 26, 34

valine, 83

values, viii, xi, 4, 6, 7, 9, 10, 13, 14, 16, 48, 60, 107,

113, 121, 123, 125, 126, 127, 128, 129, 130, 131,

177, 184

variable(s), 63, 131

variation, 59, 124, 136, 146

vascular dementia, 146, 152

vascular diseases, 53

vascular endothelial growth factor (VEGF), 13

vascular occlusion, xi, 121, 122

vasodilation, 36, 128

vasodilator, 33

vasopressor, 31

vegetables, 26, 42, 50

vegetarianism, 191

vegetarians, xiii, 176, 185

VEGF, 6, 17

vein, viii, 6, 13, 67, 76, 80

velocity, 12, 33, 107

verbal fluency, 144

versatility, xi, 95, 99, 101, 115, 117

vessels, xiii, 33, 175, 176

veterans, 36, 148

Virginia, 96

virus(es), 6, 59

viscera, 33

vision, 178

visualization, 164, 165

vitamin A, 23

vitamin B1, vii, x, xii, xiii, 1, 2, 3, 4, 40, 41, 44, 45,

46, 48, 50, 51, 52, 54, 58, 60, 61, 62, 63, 64, 65,

66, 67, 69, 70, 71, 73, 74, 76, 91, 96, 121, 123,

126, 130, 134, 139, 140, 141, 142, 143, 144, 145,

146, 147, 148, 149, 150, 151, 152, 175, 176, 177,

178, 179, 180, 181, 182, 183, 184, 185, 186, 187,

188, 189, 190, 191

vitamin B12, vii, x, xii, xiii, 1, 2, 3, 4, 40, 41, 44, 45,

46, 48, 50, 51, 52, 54, 58, 60, 61, 62, 63, 64, 65,

66, 67, 69, 70, 71, 73, 74, 76, 91, 96, 121, 123,

126, 130, 134, 139, 140, 141, 142, 143, 144, 145,

146, 147, 148, 149, 150, 151, 152, 175, 176, 177,

178, 179, 180, 181, 182, 183, 184, 185, 186, 187,

188, 189, 190, 191

vitamin B12 deficiency, vii, xii, xiii, 1, 2, 4, 40, 41,

48, 62, 63, 64, 66, 67, 71, 126, 139, 140, 143,

144, 145, 146, 147, 148, 175, 176, 177, 178, 179,

180, 181, 182, 184, 185, 186, 187, 189, 190

vitamin B2, 61, 65

vitamin B3, 23, 29

vitamin B6, viii, xi, xii, xiii, 5, 6, 7, 8, 9, 10, 13, 14,

15, 16, 17, 18, 19, 44, 45, 51, 52, 54, 59, 62, 64,

65, 66, 67, 70, 71, 76, 77, 80, 99, 119, 121, 123,

125, 126, 133, 134, 140, 149, 150, 153, 154, 156,

168, 169

vitamin B6 deficiency, 17, 19, 67, 77, 125, 126

vitamin B6 supplementation, 17, 126, 150

vitamin C, vii, 22, 23, 25, 32, 60, 184

vitamin D, vii, 23, 60

vitamin E, 31

vitamin supplementation, 51

vitamins, vii, x, xiii, 18, 22, 23, 24, 25, 26, 27, 28,

34, 35, 44, 45, 49, 50, 58, 60, 61, 62, 63, 65, 129,

130, 137, 175, 176, 180, 188

vomiting, 26, 60

vulnerability, 44

W

Wales, 130

war, 27, 35

wastewater, 86, 95, 96

wastewater treatment, 95

wastewaters, 85

weight loss, 59

white matter, 79, 179

wine, 62

Wisconsin, 26

withdrawal, 28, 30, 145

Index 211

women, 29, 43, 45, 47, 48, 50, 52, 54, 123, 150, 151,

183

workers, 2

Y

yield, 65, 92, 96, 115, 165

yolk, 32

young men, 123

young women, 45, 52

Z

Zimbabwe, 191

zinc, 31 60 

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INDEX

A

abortion, 190

AC, 51, 75, 76

access, 131, 137

accidents, 28

acetone, 84

acid, ix, x, xi, xii, 4, 28, 37, 39, 40, 41, 43, 44, 45,

46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 60, 61, 63,

64, 71, 73, 77, 80, 81, 82, 83, 84, 85, 86, 89, 90,

94, 95, 97, 100, 101, 104, 107, 108, 109, 112,

113, 114, 115, 119, 121, 124, 125, 129, 130, 133,

139, 140, 143, 144, 146, 148, 150, 151, 154, 155,

161, 163, 165, 173, 177, 186, 189

acidity, 185

activated carbon, 82

activation, 19, 67, 69, 75, 77, 87, 91, 94

active site, xi, 99, 100, 103, 107, 108, 109, 111, 112,

115, 116, 143

acute renal failure, 55, 174

adaptation, 62

addiction, ix, 22, 29, 36, 106

additives, xi, 81

adenocarcinoma(s), 78, 79

adenoma, 47, 54, 64

adenosine, 65, 117, 128, 143

adenosine triphosphate, 117

adhesion, 11

adipose, 177

adipose tissue, 177

adjunctive therapy, 70

adjustment, 72, 129

administration, 2, 30, 31, 34, 45, 55, 71, 128, 154,

182, 184

adolescence, 177

adolescents, 27, 70, 71

adrenaline, ix, 22, 24, 25

adrenochrome, ix, 22, 25, 30, 31, 32

adriamycin, 173

adults, 42, 53, 62, 78, 150, 177, 191

aetiology, x, 58, 65, 71

aetiopathogenesis, 59

Africa, 185

age(ing), ix, 22, 32, 45, 48, 53, 123, 140, 145, 147,

150, 185, 186

agent, 6, 10, 53, 154, 155, 156, 157, 166, 168, 171,

173, 183, 188

agonist, 143

AIDS, 36

alanine, xi, 99, 104, 105, 106, 107, 108, 109, 110,

111, 112, 113, 115, 116, 118, 119

albumin, 19, 122, 124, 125, 127, 129, 133

alcohol, ix, 22, 27, 28, 29, 30, 35, 36, 39, 46, 47, 54,

84

alcohol consumption, ix, 29, 39, 47

alcohol use, 47, 54

alcoholic liver disease, 43

alcoholics, 27, 28, 29, 30, 31, 35, 36, 42

alcoholism, viii, 21, 22, 24, 28, 29, 43, 181

aldehyde dehydrogenase, viii, ix, 21, 22, 24, 27, 29

alkane, 84, 87, 94, 95, 98

allele, 29

alternative(s), 91, 92, 93, 94, 100, 184

Alzheimer’s disease, ix, 39, 45, 50, 52, 145, 147,

149, 151, 152, 187

amide, 169, 171, 172

194 Index

amines, 30, 141, 163

amino acid, xi, xii, 6, 28, 41, 65, 77, 82, 88, 89, 93,

99, 100, 101, 102, 104, 109, 114, 119, 122, 133,

139, 143, 147

amino acids, xi, 28, 82, 88, 89, 93, 99, 100, 101,

102, 104, 114, 133, 143

aminosalicylates, x, 57, 58

ammonia, xi, 99, 101, 103, 165

ammonium, 103

amyotrophic lateral sclerosis, ix, 22, 30, 31, 35, 36

AN, 128

anabolism, 92

anaemia, 4, 42, 148, 177, 191

anaerobe, 97

anaerobic bacteria, 83, 87, 116

anastomosis, 62, 63, 73, 74

anatomy, 154

anemia, vii, ix, x, 4, 39, 48, 58, 64, 70, 71, 72, 126,

144, 180, 188

Anemia, 60, 188

anencephaly, 43

angiogenesis, viii, 6, 7, 13, 17, 18

animal health, 22

animal models, 68, 178

animals, x, 25, 31, 33, 46, 81, 82, 155, 156, 171

anion, 40, 129

anisocytosis, 180

anorexia, 60, 177

antacids, 181

anterior cingulate cortex, 26

antibiotic, 82, 83, 95, 181

anti-cancer, viii, 5, 6, 7, 10, 14, 17

anticancer drug, 19, 42, 158, 166, 168

anticoagulant, 44

anticonvulsant(s), 55, 150

antidepressant, 46

antidepressant medication, 46

anti-inflammatory, 34, 128, 161

anti-inflammatory agents, 161

antioxidant, 31, 50, 135

antiphospholipid antibodies, 65

antitumor, 174, 183, 190

antiviral, 173

anxiety, 28

aorta, 67

AP, 75

apathy, 145, 177

apoptosis, xii, 7, 69, 139, 143, 152, 167, 168, 179,

180, 183

apoptotic pathway, 184

aquifers, 84

arginine, 107, 118, 128

aromatic hydrocarbons, xi, 81

arteriosclerosis, 132, 143

artery(ies), xi, 33, 44, 67, 77, 121, 122, 154

arthritis, ix, 22, 34, 35, 37

ascorbic acid, 25

Asia, 147, 186

aspartate, xi, 100, 102, 113, 114, 115, 117, 119, 148

assessment, 18, 52, 71, 150

assimilation, 92

assumptions, 25

asthma, 49, 124

asymptomatic, 176, 181

ataxia, 178

Athens, 4

atherosclerosis, xii, 79, 80, 121, 122, 179

atherosclerotic vascular disease, 146

atoms, 109, 111

ATP, 96, 117, 142

atrophy, 45, 52, 145, 146, 151, 152, 177, 178, 179,

187

attachment, 17

attention, 6, 34, 44, 71, 84, 178, 180

Australia, 50

autism, 32

autoantibodies, 181

autoimmune disease, 184

autopsy, 65

availability, 91, 149

B

B vitamins, vii, 27, 45, 51, 60, 64, 70, 71, 74, 76, 80,

137, 140, 146, 147, 180, 188

Bacillus, 108, 118

bacteria, x, 59, 62, 81, 82, 83, 84, 87, 94, 97, 98,

117, 118, 119

bacterial strains, 92

bacterium, 83, 85, 95, 96, 98, 101

basal layer, 182

basement membrane, 14, 17

basic fibroblast growth factor, 13

beef, xiii, 176, 186

behavior, 154

Beijing, 170

benchmarking, 75

beneficial effect, 28, 40, 43, 130

benefits, vii, ix, xii, 3, 25, 27, 28, 31, 34, 36, 37, 39,

40, 46, 52, 122, 148, 150, 191

 

Recurrent aphthous stomatitis (RAS) is one of the most common oral mucosa lesions

seen in primary care. The most treatments given to patients suffering from RAS achieve

“short term” therapeutic goals, such as alleviation of pain, reduction of ulcer duration, and

recovery of normal oral function. Just a few reported treatments have achieved “long term”

therapeutic goals, such as reduction of the frequency and severity of RAS and maintenance of

remission Although the precise role of vitamin B12 deficiency in the pathogenesis of RAS is

unclear, suppression of cell-mediated immunity and changes in the cells of the tongue and

buccal mucosa have been reported [51,52]. We have reported previously the successful

treatment of three RAS patients with intramuscular vitamin B12 injections [53]. According to

our own clinical experience of 5 years, treatment with vitamin B12 achieves “long term”

therapeutic goals and can be effective for patients suffering from RAS, regardless of their

serum vitamin B12 level. We have begun randomized, double placebo controlled clinical

trials, which should confirm this observation.

POTENTIAL ROLE AND USES OF VITAMIN

B12 IN PREVIOUSLY UNCOMMON AREAS

A possible correlation between vitamin B12 and problems of fertility, which indicates

vitamin B12 deficiency as one of causes of recurrent abortions and the use of vitamin B12 in

initial treatments in order to prevent these conditions, has been under debate for long time

[54,55,56]. In a statistical metaanalysis performed on five studies in which serum B12 was

The Role and Status of Vitamin B12: Need for Clinical Reevaluation and Change 183

assayed in women suffering from early recurrent abortions (ERA), a significant relationship

was found between ERA and vitamin B12 deficiency [57]. No difference was noticed between

cases and controls for folate. Then vitamin B12 study should be done in ERA women whether

or not hematological or neurological abnormalities are present.

Osteoporosis is a widespread problem, which frequently has devastating health

consequences because of its association with fragility fractures. The total number of fractures,

and hence the cost to society, will increase dramatically over the next 50 years as a result of

demographic changes in the number of elderly people. Thus, prevention of osteoporosis by

identifying risk factors or risk indicators, as well as the development of new treatment

strategies, is a major health issue. Recent data suggest that vitamin B12 affects bone

metabolism, bone quality and fracture risk in humans [58]. Strokes increase the risk of

subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both

ischemic stroke and osteoporotic fractures in elderly men and women. In a population with a

high baseline fracture risk, combined treatment with folate and vitamin B12 has been shown

to be safe and effective in reducing the risk of a hip fracture in elderly patients following

stroke [59]. The relationship of Hcy and vitamin B12 with bone turnover markers, broadband

ultrasound attenuation (BUA), and fracture incidence in healthy elderly people was studied

by a few researchers, who found that high homocysteine and low vitamin B12 concentrations

were significantly associated with low BUA, high markers of bone turnover, and increased

fracture risk [60]. A preventive vitamin B12 supplementation for healthy people with

mandatory risk factors for osteoporosis and a treatment with vitamin B12 of patients suffering

from osteoporosis could be a promising treatment for this serious problem. Controlled

clinical trials should be conducted to confirm the safety and effectiveness of vitamin B12

therapy for osteoporosis.

Cobalamin carrier proteins,the transcobalamins (TC), are elevated during trauma,

infections and chronic inflammatory conditions. This remains un-explained. It is proposed

that such TC elevations signal a need for cobalamin central to the resolution of inflammation

[61]. Vitamin B12 is an effective scavenger of nitric oxide (NO) [62]. Septic shock has an

extremely high mortality rate, with approximately 200,000 people dying from sepsis annually

in the U.S. The high mortality results in part from severe hypotension secondary to high

serum NO concentrations. Reducing NO levels should be beneficial in sepsis; a possible

approach in reducing NO levels in sepsis is the use an NO scavenger, which would leave

sufficient free NO for normal physiological functions. Animal and human clinical data

suggests that high dose cobalamin may prove a promising approach to systemic inflammatory

response syndrome (SIRS), sepsis, septic and traumatic shock.

Drugs which directly counteract nitric oxide, such as endothelial receptor blockers, NOsynthase inhibitors, and NO-scavengers, not only may be effective in the acute treatment of

migraine, but also are likely to be effective in migraine prophylaxis. The first prospective,

open study indicated that intranasal hydroxocobalamin may have a prophylactic effect in

migraine [63].

A number of studies have demonstrated that cobalamin is important in maintaining

differentiation, proliferation, and metabolic status of cells. NO can cause both apoptosis and

necrosis, making it a good candidate for antitumor therapy. Initially, vitamin B12 was

proposed for use as a scavenger and cytoprotective agent to bind and inactivate NO. The use

184 Ilia Volkov, Inna Rudoy and Yan Press

of vitamin B12 as a carrier to deliver nitric oxide into tumor cells is novel. In one

investigational study was shown that complex NO-cobalamin inhibited tumor growth in vivo

and in vitro by activating the extrinsic apoptotic pathway [64].

STRATEGY FOR PREVENTION AND

TREATMENT OF VITAMIN B12 DEFICIENCY

The question regarding which patients require tests for B12 level continues to be

discussed [65]. It is not always easy to decide whether a patient suffers from vitamin B12

deficiency or not. For initial screening, measurement of serum vitamin B12 levels may suffice.

However, the test for B12 has several pitfalls [66]. Most laboratories set normal limits at 200

to 900 pg/mL, but sensitivity and specificity vary greatly, depending on the method used.

False negatives (ie, elevated levels in the presence of deficiency) can occur in true deficiency,

active liver disease, lymphoma, autoimmune disease, and myeloproliferative disorders. False

positives (i.e., low levels in the absence of deficiency) can occur in folate deficiency,

pregnancy, multiple myeloma, and excessive vitamin C intake. The measurements are quite

accurate for serum vitamin B12 levels below 100 pg/mL, but they discriminate poorly when

vitamin B12 levels are between 100 and 400 pg/mL. When values fall in this range, levels of

serum or urine MMA and homocysteine should be measured. If MMA levels are elevated,

treatment should be initiated. If homocysteine levels are elevated, other causes of the

elevation (e.g., coexisting folate deficiency) should be ruled out. However, serum MMA and

homocysteine tests are expensive, and almost certainly these investigations are not feasible in

most clinics around the world.

After the diagnosis of vitamin B12 deficiency has been established, treatment may

commence or additional tests may be done to elucidate the causes of the deficiency. Planning

the strategy for treatment involves decisions concerning dosage, means, and form of vitamin

B12 to be employed, as well as determining need for continuous follow up [67]. Today,

physicians have a choice of several inexpensive treatments that are easy to administer and

have no known side effects. Treatment should be individualized according to patient and

healthcare provider preferences. Different forms of vitamin B12 can be used, including

cyano,- hydroxyl,- and methylcobalamin. Cyanocobalamin is the only form available in the

USA. Hydroxycobalamin may have advantages due to a slower metabolism. The co-enzyme

form, methylcobalamin, is the preferred form in Japan. In most countries vitamin B12 is still

given by intramuscular injection in the form of cyanocobalamin or hydroxycobalamin. As

mentioned, practices concerning both dose and administration vary considerably.

Traditionally, vitamin B12 deficiency has been corrected by parenteral administration of the

vitamin. Intramuscular injections are safe, but may cause local discomfort. Injections are

inconvenient and more expensive due to the need for the patient to visit the doctor in the

clinic or for the provider to see the patient at home. An alternative to parenteral therapy,

lately approved by the FDA, is intranasal administration of cyanocobalamin. In Europe,

intranasal hydroxocobalamin has been widely used for years. The intranasal administration of

500 micrograms of cyanocobalamin weekly attains blood levels that are comparable to those

found with intramuscular injections. A positive clinical experience of many years in several

The Role and Status of Vitamin B12: Need for Clinical Reevaluation and Change 185

countries [68] and current results of some studies [69], which investigated the effectiveness,

safety, and acceptability of oral vitamin B12, suggest that vitamin B12 deficiency may be

treated with oral dose vitamin B12 as effectively as that with injections of vitamin B12. The

evidence derived from limited studies [70] suggests that 2000 mcg doses of oral vitamin B12

daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as

effective as intramuscular administration in obtaining short term hematological and

neurological responses in vitamin B12 deficient patients. Oral high dose vitamin B12 is

appropriate for both the replacement therapy in patients with vitamin B12 deficiency and for

maintenance treatment. Most likely oral vitamin B12 can provide an effective alternative to

intramuscular injections. Using different doses of vitamin B12 (from a few micrograms to

dozens of milligrams) is becoming more and more wide spread [30,71]. Because

approximately 1% of orally ingested B12 is absorbed via simple diffusion from the intestine

(independently of intrinsic factor), oral replacement with high doses of vitamin B12 is both

effective and safe, regardless of the etiology of vitamin B12 deficiency. Thus, in pernicious

anemia, vitamin B12 must be given in large amounts (preferably >1,000 micrograms a day).

However, in vegan patients or patients with food-cobalamin malabsorption syndrome and low

gastric acidity, oral B12 may be effective in smaller doses.

We conducted a comprehensive MEDLINE search using combinations of the following

keywords: vitamin B12, vitamin B12 deficiency, treatment with vitamin B12, cobalamin, doses

of cyanocobalamin, hydroxycobalamin, methylcobalamin, We did not find any reference

relating to explanation how a widespread dose regimen of cobalamin for treatment of

different conditions was done. As a result, we concluded that dosage was chose empirically

without solid scientific basis, and today overwhelming majority of practitioners continue to

treat their patients with dosages that were established decades ago, despite new research data

and possibilities provided by modern medicine. For example, cobalamin resistance may occur

in diabetes, renal insufficiency and advanced age, leading to functional cobalamin deficiency,

thus, requiring higher doses. In our opinion, perhaps negative results of some studies or

ineffective treatment of several conditions with vitamin B12 may be explained by insufficient

dose of cobalamin.

NECESSITY OF NEW APPROACH TO

THE PROBLEM OF VITAMIN B12

We know that not only ill individuals with special problems and vegetarians can suffer

from vitamin B12 deficiency, but also patients with low meat intake. There are many articles

indicating the increasing prevalence of low Vitamin B12 level in different segments of general

population [72,73,74,75,76,77]. In the past decade we have also become aware that vitamin

B12 deficiency occurs commonly in industrial countries at different levels of economic and

social status. A high prevalence of symptomatic vitamin B12 deficiency was discovered in a

pre-urban Bedouin area in Southern Israel due to low intake of animal products [72]. Dietary

vitamin B12 deficiency is a severe problem in India, Mexico, Central and South America [73]

and selected areas in Africa [74]. For example, at least 40% of the population in Central and

South America has deficient or marginal plasma vitamin B12 concentrations in almost all

186 Ilia Volkov, Inna Rudoy and Yan Press

areas and in all age groups [75]. As a rule, it appears to be prevalent in 30-40% of those in

the lower socioeconomic levels. Our clinic serves middle to upper-middle class population,

and, according to preliminary data received in our study, frequency of deficient or marginal

vitamin B12 level (<250pg/ml) was about 35%. We cannot extrapolate our finding to general

population in this area, because the study population is a selected sample, but we suppose

that a prevalence of low level of vitamin B12 in the overall population may be similar. Today

there is a tendency in modern society to change habits, for example cessation of smoking,

"fighting" with overweight, accentuating physical exercise, adopting correct eating habits.

We have come to the conclusion that as a result of media information disseminating the

relationship between meat, cholesterol and cardiovascular diseases, consumption of meat,

particularly beef, has decreased. We suppose that the decrease of level of vitamin B12 in the

population with higher educational level is caused by a premeditated decrease in

consumption of animal products. Also in modern society there is a tendency for ideological

motives, particularly among the younger generation, to be vegans. Changes in life style

among segments of the population with high socioeconomic level, on one hand, and the

existence of poverty, on the other, are two main factors in the decreasing consumption of

animal products (particularly red meat). This causes a decrease in the level of vitamin B12 in

general population, and as a consequence, this will increase pathology due to vitamin B12

deficiency (such as neurological and hematological disorders). As mentioned, vitamin B12

deficiency has various and serious health effects. In lieu of these possible developments and

in order to prevent serious health problems, Vitamin B12 routine fortification should be

seriously considered and discussed.

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