Essential and Toxic Trace Elements and Vitamins in Human Health

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Essential and Toxic Trace
Elements and Vitamins in
Human Health
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Contributors
Acknowledgments
Periodic table of the elements
Introduction
Part I: Essential
1
Clinical and immunological effects and biomarkers of zinc deficiency
	Introduction
	Discovery of zinc deficiency in human
		Studies in Iran
		Studies in Egypt
		Chronology of other important observations in human zinc deficiency
	Clinical effects of zinc deficiency
		Severe
		Moderate
		Marginal
	Biochemical and immunological effects of zinc
		Zinc and enzymes
		Zinc and hormones
			Growth
			Gonadal function
			Insulin and diabetes
			Prolactin
		Zinc and immunity
		Zinc and cell membrane
		Metallothionein
		Zinc and gene expression
		Interactions of zinc with other elements
		Zinc and free radicals
	Biomarkers of zinc deficiency
		Studies in Egypt
		Atomic absorption spectrophotometry for assaying zinc in biological samples
		Development of biomarkers of zinc deficiency in experimental human zinc deficiency model
		Zinc in plasma and blood cells
		Changes in zinc-dependent enzymes
		Serum thymulin activity as a biomarker of human zinc deficiency
		Development of immunological biomarkers of human zinc deficiency
		Endogenous excretion of zinc as a biomarker of zinc deficiency
	Clinical impact of zinc
		Zinc in infections
			The common cold and other viral infections
			Bacterial infections
			Parasitic infections
			Diarrhea
		Genetic disorders
			Zinc and sickle cell disease (SCD)
			Acrodermatitis enteropathica (AE)
			Wilsons disease
		Renal disease and zinc
		Age-related macular degeneration (AMD) and zinc
		Zinc in the elderly
	References
	Further reading
2
Zinc and the immune system: Insights into the role of zinc in autoimmune diseases
	Introduction
	Autoimmune diseases
	Zinc signaling
	Effect of zinc on the immune system
		Innate immunity
			Granulocytes
			Monocytes and macrophages
			Dendritic cells
			Mast cells
			Natural killer cells
			Membrane barriers
			Peptidoglycan regulation proteins
			Nutritional immunity
		Adaptive immunity
			T cells
			B cells
	Conclusion
	References
3
Zinc transporters in physiology and pathophysiology
	Zinc as an essential mineral for life
		Zinc signaling and zinc stress
		Zinc level in organelles
	Zinc homeostasis by zinc transporters and their biological relevance
		Physiology and pathophysiology of ZnT family members
		ZIP physiology and pathophysiology
	Recent advances of investigation of zinc transporters and skin disorders
		Epidermis
		Dermis
	Conclusions and perspectives
	References
4
Copper
	Introduction
	Wilsons disease
		Introduction
		Clinical presentation, recognition, and diagnosis
		Treatment
	Menkes disease and ATP7A-related copper transport diseases
		Introduction
	Menkes disease
		Diagnosis
		Treatment
	Occipital horn syndrome
	ATP7A-related distal motor neuropathy
	Copper toxicity in Alzheimers disease
	The potential benefits of ``copper lowering therapy´´ in a variety of diseases
		Cancer
		Fibrotic, inflammatory, and autoimmune diseases
	Clinical copper deficiency
	References
5
Iron
	Biochemical properties of iron
	Iron homeostasis
		Dietary iron absorption
			Dcytb and DMT1
			Ferroportin
			Ferroxidases
		Iron in the circulation
			Transferrin
			Non-transferrin bound iron
		Uptake of iron by erythroid cells and synthesis of heme
		Iron processing by macrophages
		Cellular iron
		Systemic regulation of iron homeostasis by hepcidin
			Function of hepcidin
			Regulation of hepcidin by iron status
			Regulation of hepcidin by inflammation
			Regulation of hepcidin by erythropoiesis
	Imbalances in iron homeostasis
		Iron deficiency
			TMPRSS6
		Increased iron stores and iron overload
			HFE mutations and other genetic conditions leading to hepcidin deficiency
				HFE hemochromatosis
				TfR2 hemochromatosis
				Juvenile hemochromatosis
				Treatment of hereditary hemochromatosis
			Ferroportin iron overload-Hepcidin resistance and other forms
			Aceruloplasminemia
			Hypotransferrinemia
			DMT1 mutations
			Ineffective erythropoiesis
			Transfusional iron overload
			Dysmetabolic iron overload syndrome
			African dietary iron overload
	Conclusion
	References
6
Iodine
	Introduction
	Epidemiology of iodine deficiency
	Assessment of iodine status
		Urinary iodine concentration
		Thyroglobulin (Tg)
		Thyroid stimulating hormone and thyroid hormones
		Dietary assessment
		Future research
	Consequences of residing in iodine-deficient regions
	Consequences of mild to moderate iodine deficiency
	Iodine supplementation
		Delivering effective iodine supplementation
	Iodine excess
	Iodine metabolism and its role in metabolism
		Overview
		Endocrine disruptors
		Iodine and auto-immunity
		Iodine and its role in epigenetics
	Conclusion
	References
7
Selenium
	Introduction
	Dietary selenium intake
		Deficient intake
		Excessive intake
		Dietary recommendations
	Selenium biomarkers
		Plasma
		Whole blood
		Urinary selenium excretion
		Nail and hair selenium concentrations
		Determinants of selenium biomarkers
	Selenoproteins, biological functions, and potential health effects
	Health effects
		Mortality
		Cancer
		Cardiovascular disease
		Stroke and other neurological diseases
		Type 2 diabetes
		Thyroid function
		Immune system
		Other health effects
	Knowledge gaps
	References
8
Unifying mechanisms of trivalent chromium in health and disease
	Introduction
	Clinical benefits of chromium supplementation
	New mechanistic aspects of chromium action
		Cholesterol toxicity
		Hexosamine toxicity
		Inflammatory response and vascular function
		Oxidative stress
	Conclusion
	References
9
Manganese
	Introduction
	Essentiality
		Sources
		Kinetics
			Absorption
			Distribution
			Elimination
		Mn functions
		Mn deficiency
	Toxicity
		Sources and routes of exposure
		Neurotoxicity
			Dopaminergic system
			GABAergic system
			Cholinergic system
			Glutamatergic system
		Mitochondrial dysfunction
		Epigenetics
		Other conditions
	Conclusions
	References
10
Fluorine in human metabolism, health and disease
	Introduction
	Routes of fluoride exposure
	Atmospheric fluoride
	Terrestrial fluoride
	Hydrospheric fluoride
	Food
	Fluorine metabolism
	Fluorine in human health and disease
		Oral health
	Biochemistry of fluorapatite formation
	Fluoride toxicity
	Osteoporosis
	Skeletal fluorosis
	Neurological effects
	Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR)
	Summary
	References
Part II: Toxic trace elements
11
Arsenic skin carcinogenesis: A prototypic model of chemical carcinogenesis featured with abnormal differentia ...
	Introduction
	The plausible mechanism of arsenic carcinogenesis
	Mechanisms of arsenic-induced skin cancer
	Abnormal epidermal differentiation in arsenical cancers
	Abnormal proliferation and apoptosis in arsenical cancers
	Aberrant immune responses by arsenic
	References
12
Emerging importance of manganese and arsenic as modifiers of cadmium accumulation
	Introduction
	Cd accumulation in the kidney among rice-eating human populations
	Transport of Cd and Mn via Zn transporters in mammals
	Cd uptake via Mn transporter in rice
	Trade-off relationship of Cd and As accumulation in rice
	Conclusions
	References
13
Lead
	Introduction
		Occurrence in nature
		Properties
		Uses
		Intake and metabolism
	Biological effects
		Hematopoietic effects
		Effect on the cardiovascular system
		Effect on the neurological system
		Effect on the renal system
		Effect on other organ systems
	Treatment of Lead poisoning in humans
	References
	Further reading
14
Methylmercury: Human exposure, animal behavior, and insight on molecular mechanism
	Introduction
	Environmental toxicant
	Human exposure
		Minamata disease
		Epidemiology
	Animal behavior
	Mechanism(s) of toxicity
	Conclusion
	References
	Further reading
Part III: Vitamins
15
Vitamin A
	Introduction
	Metabolism and regulation
		Digestion and absorption
			Preformed vitamin A
			Carotenoids
		Transport
			Plasma transport after meals
			Plasma transport of retinol
			Intracellular transport
		Hepatic uptake, storage, and secretion
		Recycling/conservation (recycling and renal reuptake)
			Retinol recycling and reuptake after renal filtration
		Oxidative metabolism and excretion
			Synthesis of retinal and retinoic acid from retinol
			Polar and oxidized metabolites of retinoids
		Nuclear activity of retinoic acid
	Vitamin A requirements
		Vitamin A deficiency
		Vitamin A toxicity
		Assessment of vitamin A status
	Vitamin A in the life cycle
		Vitamin A status at birth
			Transfer in milk
	Current nutritional recommendations
	References
16
The B-vitamins
	Vitamin B1 (thiamin)
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous aspects
		Toxicity
	Vitamin B2 (riboflavin)
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous aspects
		Toxicity
	Vitamin B3 (niacin)
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous aspects
		Toxicity
	Vitamin B6
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous issues
		Toxicity
	Vitamin B12
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous issues
		Toxicity
	Folate
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous issues
		Toxicity
	Pantothenic acid
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous issues
		Toxicity
	Biotin
		Physiology
		Dietary sources
		Status assessment
		Deficiency
		Miscellaneous issues
		Toxicity
	References
17
Vitamin C
	Chemistry and biochemistry
		Ascorbic acid chemistry, measurement, and catabolism
		Chemistry: Synthesis in animals-In vivo
		Chemistry: Synthesis in vitro
		Ascorbic acid: Chemical reductant in vivo and in vitro
		Ascorbic acid biochemistry: Reduction reactions: Enzymology
	Transport
		Ascorbic acid
		Dehydroascorbic acid
		Transmembrane electron transfer
	Physiology and pharmacokinetics of vitamin C in humans: Tight control of vitamin C concentrations
		Background
		Physiology and pharmacokinetics: Plasma concentrations and tight control
		Bioavailability
		Transport in vivo
		Renal reabsorption and excretion
		Utilization
		Physiology and pharmacokinetics studies of vitamin C: Limitations
	Pharmacology and pathophysiology
		Background
		Cancer treatment
		Sepsis and acute respiratory distress syndrome
		Diabetes, dehydroascorbic acid, and red blood cells
	Vitamin C consumption in humans
		Dietary sources of vitamin C
		Dietary Reference Intakes and use categories
		Special considerations for Dietary Reference Intakes
		Limitations
	Deficiency and excess
		Vitamin C deficiency: Etiologies of deficiency, therapy
		Vitamin C excess: Adverse effects
	References
18
Vitamin D in human health
	Biology and metabolism
	Definition of vitamin D deficiency
	Causes of vitamin D deficiency
		Exposure to sunlight and cutaneous factors
		Cutaneous factors
		Bioavailability of vitamin D after oral ingestion or cutaneous synthesis
			Fat malabsorption
			Obesity
			Liver disease
			Kidney disease
			Metabolism of vitamin D increase
	Vitamin D deficiency and disorders
		Musculoskeletal consequences of vitamin D deficiency
			Vitamin D and bones
			Rickets
			Osteoporosis and osteomalacia
			Muscle weakness and falls
		Nonmusculoskeletal consequences of vitamin D deficiency
			Immunomodulatory functions
				Autoimmune diseases
					Rheumatoid arthritis
					Inflammatory bowel disease
					Multiple sclerosis
					Asthma
					Type 1 diabetes
					Systemic lupus erythematosus
				Infectious diseases
			Cancers
			Cardiovascular disease
			Neuropsychological functioning
		Vitamin D toxicity
	Conclusion
	References
19
Vitamin E: Tocopherols and tocotrienol and their role in health and disease
	Introduction
	Vitamin E as dietary supplements
	Is RDA for α-tocopherol set at an appropriate level?
	RDA for tocotrienols
	Tocopherol and tocotrienol status/intake in obesity and metabolic syndrome
		Obesity and metabolic syndrome
	α-Tocopherol supplementation in obese individuals
	Tocotrienol status/intake in obesity
	Vitamin E in diseases and health
		Vitamin E deficiency
		Vitamin E in health
			Vitamin E and neuroprotective functions
			Vitamin E in folliculogenesis and wound healing
			Non-alcoholic fatty liver disease (NAFLD) or NASH
			Cancer
			Other effects of vitamin E
	Conclusion
	References
Recommended daily dietary allowances
Recommended daily dietary allowances
Index
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