Essential and Toxic Trace Elements and Vitamins in Human Health

George J. Brewer,Ananda S. Prasad

• Editore: Academic Press
• Anno: 2020
• ISBN:
  9780128093016
• Argomento: Medicina
• Categoria: Enfermería

Essential and Toxic Trace Elements and Vitamins in Human Health is a comprehensive guide to the wide variety of micronutrients that affect human health, including fat-soluble and water-soluble vitamins that support diverse biochemical functions, trace elements with established and suggested links to health maintenance, and elements with known human toxicity such as arsenic, cadmium, and lead.

An essential reference text for nutritionists working in academia and functional food and supplement industries, dieticians, and clinicians, Essential and Toxic Trace Elements and Vitamins in Human Health provides an in-depth look at toxic trace elements and essential vitamins and minerals and their direct influence on the body's overall health with expert research from renowned scientists.

• Presents a balanced scientific view of essential and nonessential micronutrients with an in-depth analysis of the biochemical functions each plays in human health
• Examines particular micronutrients in detail with coverage of clinical aspects, interaction with other micronutrients, immunological effects, cognitive functions and epigenetics
• Focuses on effective management of micronutrient deficiencies and on toxicity implications of overexposure

Part I

Essential

Chapter 1

Clinical and immunological effects and biomarkers of zinc deficiency

Ananda S. Prasad Distinguished Professor of Oncology, Wayne State University and Karmanos Cancer Center, Detroit, MI, United States

Abstract

Zinc as an essential element for humans was recognized in 1963. Nutritional zinc deficiency is now known to affect more than 2 billion human subjects globally. Zinc is an intracellular signaling molecule and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an antiinflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases, concurrent zinc deficiency may complicate the clinical features, adversely affect immunological status, increase oxidative stress, and increase the generation of inflammatory cytokines. It is currently believed that oxidative stress and chronic inflammation may have important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and autoimmune diseases. It is therefore important that the status of zinc is assessed and zinc deficiency corrected in these chronic conditions. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is recommended.

Keywords

Zinc; Interleukin-2; TNF-α; A-20; Thymulin

Chapter outline

• 1 Introduction
• 2 Discovery of zinc deficiency in human
  • 2.1 Studies in iran
  • 2.2 Studies in Egypt
  • 2.3 Chronology of other important observations in human zinc deficiency
• 3 Clinical effects of zinc deficiency
  • 3.1 Severe
  • 3.2 Moderate
  • 3.3 Marginal
• 4 Biochemical and immunological effects of zinc
  • 4.1 Zinc and enzymes
  • 4.2 Zinc and hormones
  • 4.3 Zinc and immunity
  • 4.4 Zinc and cell membrane
  • 4.5 Metallothionein
  • 4.6 Zinc and gene expression
  • 4.7 Interactions of zinc with other elements
  • 4.8 Zinc and free radicals
• 5 Biomarkers of zinc deficiency
  • 5.1 Studies in Egypt
  • 5.2 Atomic absorption spectrophotometry for assaying zinc in biological samples
  • 5.3 Development of biomarkers of zinc deficiency in experimental human zinc deficiency model
  • 5.4 Zinc in plasma and blood cells
  • 5.5 Changes in zinc-dependent enzymes
  • 5.6 Serum thymulin activity as a biomarker of human zinc deficiency
  • 5.7 Development of immunological biomarkers of human zinc deficiency
  • 5.8 Endogenous excretion of zinc as a biomarker of zinc deficiency
• 6 Clinical impact of zinc
  • 6.1 Zinc in infections
  • 6.2 Genetic disorders
  • 6.3 Renal disease and zinc
  • 6.4 Age-related macular degeneration (AMD) and zinc
  • 6.5 Zinc in the elderly
• References
• Further reading

1 Introduction

Raulin (1869) showed for the first time that zinc was essential in biological systems, and they demonstrated that zinc was required for the growth of Aspergillus niger. Zinc was shown to be essential for higher plants (Sommer and Lipman, 1926). Todd et al. (1934) reported that zinc was essential for rats. In 1955, a disease called parakeratosis in swine was reported (Tucker and Salmon, 1955) due to a deficiency of zinc. The essentiality of zinc for the growth of chickens was shown (O’Dell et al., 1958). In animals, the manifestations of zinc deficiency included growth failure, loss of hair, thickening and hyperkeratinization of the epidermis, and testicular atrophy. Deficiency of zinc in breeding hens resulted in decreased hatchability, gross embryonic anomalies characterized by abnormal skeletal development, and weakness in chicks that hatched (Blamberg et al., 1960). Although the essentiality of zinc for animals was established, its ubiquity made it seem improbable that zinc deficiency in humans could lead to significant problems in clinical medicine. During the past 50 years, however, it has become apparent that deficiency of zinc in humans is prevalent.

2 Discovery of zinc deficiency in human

2.1 Studies in Iran

I arrived in Shiraz, Iran, in June 1958. I received my training in internal medicine as a clinical scientist at the University of Minnesota School of Medicine, under Dr. C.J. Watson, a superb teacher, an excellent clinician, and a great scientist. Dr. Hobart A. Reimann, who had preceded Dr. Watson as Chief of Medicine at Minnesota, was appointed as Chief of Medicine at Nemazee Hospital, University of Shiraz Medical School. Dr. Reimann invited me to join him in Iran to set up a curriculum for teaching medicine to students and house staff.

In Shiraz, I met Dr. James A. Halsted, who was a Fulbright Professor at University of Shiraz Medical School and was primarily involved with Saadi Hospital, an equivalent of a charitable city hospital in the United States. In the fall of 1958, I was invited by Dr. Halsted to discuss a patient at the medical center grand rounds at the Saadi Hospital. The patient was a 21-year-old male who looked like a 10-year-old boy and who was severely anemic. The chief resident, Dr. M. Nadimi, a graduate of the Shiraz Medical School, presented the case to me.

The patient had severe iron deficiency anemia but there was no blood loss. Severe iron deficiency without blood loss in adult males is very uncommon. Other clinical manifestations were hypogonadism, hepatosplenomegaly, rough and dry skin, mental lethargy, and geophagia. The patient ate only bread from wheat flour and the intake of animal protein was negligible. He consumed nearly 0.5 kg of clay daily. The habit of geophagia (clay eating) was common in the villages around Shiraz. We documented iron deficiency anemia in our patient. Ten additional similar cases were brought to the hospital on my service within a short period, and hypopituitarism as an explanation for growth retardation and hypogonadism was considered to be unlikely (Fig. 1).

Fig. 1 A picture of four dwarfs from Iran. From left to right: (1) age 21, height 4 ft. 11½ in; (2) age 18, height 4 ft. 9 in; (3) age 18, height 4 ft. 7 in; (4) age 21, height 4 ft. 7 in. Staff physician on left is 6 ft. (Reprinted with permission from Prasad, A. S., 1966. Metabolixm of zinc and its deficiency in human subjects, In: Prasad, A.S. (Eds.), Zinc Metabolism. Thomas, Springfield, IL, p. 250.)

The anemia of the subjects responded promptly to oral administration of iron. The probable factors responsible for anemia were insufficient available iron in the diet, excessive sweating probably causing greater iron loss from the skin than would occur in a temperate climate, and geophagia further decreasing iron absorption as shown later (Minnich et al., 1968). After therapy with orally administered ferrous sulfate (1 g/d) and a nutritious hospital diet containing adequate animal protein, the anemia was corrected, hepatosplenomegaly improved, subjects grew pubic hair, and genitalia size increased (Prasad et al., 1961). Liver-function tests were unremarkable except for the serum alkaline phosphatase, which increased after treatment. Retrospectively, one might explain this observation on two bases: (1) ordinary pharmaceutical preparation of iron might have contained appreciable quantities of zinc as a contaminant; and (2) animal protein in diet most likely supplied available zinc, thus inducing the activity of alkaline phosphatase, an established zinc metalloenzyme.

It was difficult to explain all of the clinical features solely by tissue iron deficiency, as growth retardation and testicular atrophy are not seen in iron-deficient experimental animals. The possibility that zinc deficiency may have been present was considered. Zinc deficiency was known to produce growth...