Consequences of Mineral and Deficiencies

1. Consequences of Mineral and Deficiencies Part I

2. KEY FACTORS IN MINERAL RESERACH Rule: There is no stronger evidence of a mineral’s necessity than the symptoms one observes when the dietary levels are below adequacy Rule: Whereas a biomarker can assess the early consequences of a deficiency, a pathology that develops as a result of the deficiency is a defining factor Rule: Observing the consequences of a severe omission is secondary in importance to easing or removing the symptoms upon repletion of the mineral

3. Key Factors in Mineral Deficiencies Rule: Unlike vitamins mineral deficiency symptoms tend to be ambiguous with the same symptom appearing for more than one mineral Rule: Many macrominerals have no deficiency signs Rule: Most of the attention in nutrition is on micro-mineral deficiencies

4. Typical Signs of Mineral Deficiencies Inward Signs Outward Signs 1. Stunted growth 1. Anemia 2. Neutrapenia 2. Skin rash 3. Hematocrit 3. Pigment change 4. Impaired digestibility, diarrhea 4. Alopecia (hair loss) 5. Immune system compromise 5. Physical stamina 6. Enzyme dysfunctions 6. Skeletal weakness 7. Hormonal dysfunctions 7. Impaired mobility 8. Unchecked peroxidations, hypertension 8. Loss of mental acuity 9. Impaired genetic expression 9. Lack of coordination 10. Premature aging 10. Disease susceptibility

5. K Potassium

6. K Potassium Deficiency • Potassium deficiency is the most common electrolyte imbalance. • It is more often caused by excessive losses than by deficient intakes. • Conditions such as diabetic acidosis, dehydration, or prolonged vomiting or diarrhea can create a potassium deficiency. For this reason, many physicians prescribe potassium supplements with these potassium-wasting drugs. • One of the earliest symptoms is muscle weakness

7. K Potassium & Hypertension • Diets low in potassium seem to play an important role in the development of high blood pressure. • Low potassium intakes raise blood pressure, whereas high potassium intakes appear to both prevent and correct hypertension. • Potassium-rich fruits and vegetables also appear to reduce the risk of stroke-more so than can be explained by the reduction in blood pressure alone.

9. Ca Calcium

10. Ca Deficiency • A negative Ca balance occurs when net Ca absorption is unable to replace losses • The most dramatic symptoms are stunted growth, poor quality of bones and teeth and malformation of bones • Hypocalcaemia (low serum Ca in the blood) cause the hyperexcitability of the nervous system • Osteomalacia (softening of bone), tetany (muscle spasms) and kidney stones are other calcium related disorders • Osteoporosis occurs when bone resorption exceeds formation Mainly in women Increases in age May be related to a low Ca intake

11. Ca Calcium Deficiency and Bone Calcium supplements can help prevent osteoporosis, which is a condition that occurs when bone breaks down more quickly than it is replaced. In this illustration, the bone above is normal, but the bone below is more porous and therefore more susceptible to fracture.

12. Mg Magnesium

13. Mg Rule: Because of its wide variety of uses in a biological system, a deficiency in magnesium can lead to a multitude of biochemical and symptomatic changes. Rule: Although magnesium deficiency is not likely to occur in healthy people, it is still be at the root of many clinical disorders

14. Deficiency Mg • Changes is nerve & muscle function such as muscle weakness or spasm. • Heart conditions such as arrhythmia, irregular contractions, and increased heart rate. • Weakening of the bones • Imbalanced blood sugar • Elevated blood pressure • High excitability • Brain damage • Unstable internal cell structure • Inadequate hormone production • Headaches • Seizures • Depression • Nausea • Vomiting • Lack of appetite

15. Deficiency Mg

16. Causes of Deficiency Mg • Chronically low intake of Mg • Gastrointestinal system disorders that cause a loss of Mg or limit Mg absorption • Excessive loss of Mg in the Urine which could be due to: -Use of Diuretics, some antibiotics, and some medicines used to treat cancer -Alcohol consumption -Poorly controlled diabetes

17. Fe Iron and Anemia

18. Fe • Iron deficiency (50% of the population in some countries) a. Impairs red cell production b. Affects general cell growth and differentiation, specifically cells of the nervous system and intestine c. Characterized by cells that are both microcytic (small) and hypochromic (low color) 2. Children between ages of 6 and 18 months are more susceptible a. 10 times the adult requirement at this time b. Milk is generally a poor source of iron (1) An iron deficiency will develop if milk is the sole source of infant iron after 4 months c. An anemic child tends to be tired and inattentive, motor skills are delayed, mental retardation, emotional problems are evident

19. Fe Anemia and pregnancy Rule: Pregnant women have double the adult requirement 1. Most of the additional iron is transferred to the fetus Other Causes of anemia: 1. Lack of vitamin B12 or folate 2. Megaloblastic anemia: release of precursors megalokaryocytes into the blood 3. Pernicious anemia: antibodies to intrinsic factor (B12 absorption) 4. Beta Thalassemia: imbalance in the production of alpha and beta subunits of hemoglobin 5. Lead poisoning 6. Intrinsic copper deficiency

20. Fe Mineral Composition of Mammalian Milk Human Bovine Rat Mg/Liter Mg/Liter Calcium 5645  879 Sodium 1228  126 Potassium 2669  429 Iron 15  2 Copper 7  2 Zinc 29 6 Manganese 979  363 Calcium 259  59 1180 Sodium 207  94 580 Potassium 543  78 1400 Iron 0.4-0.76 0.2-0.06 Copper 0.2-0.4 0.05-0.2 Zinc 1-3 4 Manganese 3-6 21 Magnesium 31.4  5.9 120 Phosphorus 142  25 930 Chloride 453  53 1040 Selenium (ng/g) 15-20 10 Iodine (ng/g) 12-178 70-219 Molybdenum (ng/g) 1-2 22 Chromium (ng/g) 0.2-0.4 5-15 Nickel (ng/g) 0.5-2 4-40 Aluminum (ng/g) 4-14 27 Fluorine (ng/g) 4-15 19 after Reichlmayr-Lais and Kirchgessner When it comes to minerals, milk is far from being nature’s perfect food After Picciano

21. Consequences of Zn Deficiency Zn Early observations 1. Stunted growth 2. Arrested sexual maturation (hypogonadism) 3. Skin rash (acrodermatitis enteropathica) 4. Hair loss (alopecia) 5. Immune system compromise (anergy) 6. Impairment in cognitive development and awareness More Recent 1. Apoptosis induction 2. DNA stability 3. Malignant transformations 4. Impaired genetic expression

22. Zn Zinc

23. Zn • American Journal of Clinical Nutrition, Vol 20, 422-442, 1967 • Human Zn Deficiency, Endocrine Manifestations and Response to Treatment • HAROLD H. SANDSTEAD M.D.1, ANANDA S. PRASAD M.D., PH.D.1, ARTHUR R. SCHULERT PH.D.1, ZOHEIR FARID M.D., D.T.M.A., M.R.C.P.1, AUGUST MIALE JR. M.D.1, SAMIR BASSILLY M.B.1, and WILLIAM J. DARBY M.D., PH.D.1 • Division of Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37203 • Zndeficiency in the human may result in growth retardation and hypogonadism. The patients resemble those with idiopathic hypopituitarism. • 2) Treatment with Zn is followed by increased growth and sexual maturation which exceeds the changes resulting from an adequate diet or iron therapy. • 3) It appears that Zn is a limiting essential nutrient in this syndrome and may, therefore, be one of the etiobogic factors which contributes to the retarded growth and sexual maturation seen in children from the tropics and subtropics. • 4) Iron deficiency frequently is also present in these patients but does not appear to be an essential factor in the pathogenesis of the illness.

24. Zn Zn and Skin Rash

25. Zn Zn and Cognitive Development Zn is involved in all phases of mental development and function Testament to this is seen in brain disorders and cognitive development arrest in malnourished individuals. These individuals regardless of age seem to gain back their mental acuteness when given supplements of Zn.

26. Zn Harold Sandstead Zn from vesicles in presynaptic terminals of certain glutaminergic neurons modulate postsynaptic receptors for glutamate. Large amounts of Zn released from vesicles by seizures or ischemia can kill postsynaptic neurons. Acute Zn deficiency impairs brain function of experimental animals and humans. Zn deficiency in experimental animals during early brain development causes malformations, in later brain development it impairs cognitive function. This could occurs in humans.

27. Zn James G. Penland Zn supplementation of young children was assessed in Chinese children (aged 6-9 years) treated daily with 20 mg Zn alone (Zn), Zn plus micronutrients (Zn+M) or micronutrients alone (M) in a double-blind manner for 10 wks. In 740 urban children, compared to treatment with M, treatment with Zn+M or Zn was associated with improved attention (continuous vigilance task), reasoning (oddity task) and psychomotor function (tapping and tracking tasks). In 540 rural children, compared to either M or Zn alone, treatment with Zn+M resulted in greater improvement in perception (object search), reasoning (oddity task) and manual dexterity (finger tapping). Compared to M alone, Zn alone resulted in greater improvement in memory for both objects and complex shapes.

28. Zn Effects of Zn supplementation on cognitive function in healthy middle-aged and older adults: the ZENITH study Maylor, EA, Simpson, EEA, Secker, DL, Meunier, N, Andriollo-Sanchez, M, Polito, A, Stewart-Knox, B, McConville, C, O'Connor, JM, Coudray, C British Journal of Nutrition, 96, (4), 2006, 752-760 A randomized double-blind placebo-controlled design was employed to investigate the effects of Zn supplementation on cognitive function in 387 healthy adults aged 55-87 years. Several measures of visual memory, working memory, attention and reaction time were obtained at baseline and after 3 and 6 months of 0 (placebo), 15 or 30 mg Zn/d. Younger adults (<70 years) performed significantly better on all tests than older adults (>70 years), and performance improved with practice on some measures. For 2 out of 8 dependent variables, there were beneficial effects (at 3 months only) of both 15 and 30 mg/d on one measure of spatial working memory and a detrimental effect of 15 mg/d on one measure of attention.

29. Zn Zn and Cell Survival Why a Zn deficiency, severe or moderate, is detrimental to cells is a problems that is yet to be resolved. It is clear that Zn is involved in the ebb and flow of nutrients in a cell that strives to maintain homeostasis as it carries out its essential functions. Interrupting the flow of Zn or adding more free Zn to the internal milieu somehow sends a distress signal Most of the Zn in a cell is located in the cell nucleus, which bespeaks strongly for the Zn as a factor in chromatin stability and genetic expression

30. Zn Pamala J. Fraker Professor Michigan State University Nanomoles of free Zn can induce apoptosis in a variety of cells. Release of Zn within cells may cause neurological damage and other situations where cells are under stress. Inadequate dietary Zn can also lead to lymphopenia (reduced number of lymphocytes in the blood) which is a consequence of impaired lymphopoiesis (white blood cell synthesis) related to an increase in apoptosis (cell death) among precursor T and B-cells. This may reflect chronic production of glucocorticoids induced during Zn deficiency.

31. Zn Zn and Malignant Transformation Combining human and animal studies with cell culture studies has established a link between Zn deficiency and cancer. Compared with healthy people, Zn status is compromised in cancer patients. As yet it is not known if compromised Zn status is before or after the fact. According to one theory, oxidative DNA damage and chromosome breaks that have been reported in animals fed a low Zn diet lead to an increased susceptibility to tumor development when exposed subsequently to carcinogens. Zn supplementation beyond a dose of 40 mg/day or for long duration at lower levels may induce cancer

32. Zn Zn and the Prostate Gland Zn appears to be important for maintaining prostate health, but the precise function of Zn in the prostate is unknown. For reasons not yet clear, a normal human prostate accumulates the highest level of Zn of any soft tissue in the body. However, cancerous prostates have much less Zn than normal prostates, and several studies have implicated impaired Zn status in the development and progression of prostate malignancy. There is also some evidence that increased dietary Zn is associated with a decrease in the incidence of prostate cancer. Chromosomal Stability and Zn Supplementation In various cell types changes in intracellular Zn dramatically affects DNA damage and repair, and, hence, the risk of cancer. Quite possibly dietary Zn deficiency will increase the risk of oxidative DNA damage in prostate cells. Zn supplements may not only aid in the prevention of cancer, but could also play an important role in limiting its malignancy. As an antioxidant and a component of many DNA repair proteins, Zn plays an important role in protecting DNA from damage. Zn also functions as an anti-inflammatory agent. Thus, Zn supplementation has the potential to target multiple points of the carcinogenesis cascade. How effective Zn supplements are in preventing prostate cancer is controversial. Although several studies have shown that high cellular Zn levels inhibit prostate cancer cell growth, a recent epidemiological study showed an increased risk for prostate cancer in men who took high-dose Zn supplements. Increased cancer risk was seen with over 100 mg/day or long-term (more than 10 years) of Zn supplement use. The current tolerable upper intake level for Zn is 40 mg/day, established by the U.S. Institute of Medicine. Thus, it is possible that the subjects in the epidemiological study could have been in the toxic range of Zn intake. As with most therapeutics, higher doses do not always equate with an increase in efficacy.

33. Zn Zinc, infections, and wound healing The immune system is adversely affected by even moderate degrees of Zn deficiency. Severe Zn deficiency depresses immune function. Zn is required for the development and activation of T-lymphocytes, a kind of white blood cell that helps fight infection. When Zn supplements are given to individuals with low Zn levels, the numbers of T-cell lymphocytes circulating in the blood increase and the ability of lymphocytes to fight infection improves. Studies show that poor, malnourished children in India, Africa, South America, and Southeast Asia experience shorter courses of infectious diarrhea after taking Zn supplements (29). Amounts of Zn provided in these studies ranged from 4 mg a day up to 40 mg per day and were provided in a variety of forms (Zn acetate, Zn gluconate, or Zn sulfate) (29). Zn supplements are often given to help heal skin ulcers or bed sores (30), but they do not increase rates of wound healing when Zn levels are normal.

34. Stinky zinc problem Is your cologne too strong? If so you may have a zinc deficiency. University of Tennessee research discovered that nearly 80% of a group of women and men who unknowingly sprayed on too much cologne or per-fume had low blood levels of zinc. But, after six months of being fed a 50 mg daily dose of zinc gluconate, their sense of smell returned, and most cut back on their scent. About 20% to 25% of smell and taste problems are zinc-related says Thomas Namey, M.D., the researcher in the study.