Trace Elements

1. Trace Elements Reed A Berger MD Visiting Clinical Professor in Nutrition

2. Trace Elements • -a naturally occurring, homogeneous, inorganic substance required in humans in amounts less than 100 mg/day

3. Copper • -found in the liver, brain, heart, kidneys, and muscle • -about 90% of copper in the plasma is in the form of ceruloplasmin • -the rest is bound to albumin, transcuprein, and AA’s

4. Functions • -component of many enzymes • -oxidation of Fe prior to transport in the plasma • -cross-linking of collagen • -mitochondrial energy production, protection from oxidants, etc…

5. Absorption, Transport, Excretion • -some absorption from the stomach, but most in the small intestine • -absorption varies—it decreases with increased intake

6. Metabolism • -for short term transport to the liver copper is carried primarily by albumin • -copper-albumin complex acts as a temporary storage site for copper • -in the liver, metallothionein is the storage site • -ceruloplasmin is the storage site in the plasma and cells

7. -secreted from the liver as a component of bile • -once in the GI tract, it becomes part of the body’s pool and is reabsorbed or excreted depending on the body’s need • -biliary excretion increases in response to copper overload • -small amts of copper are present in the urine, sweat, and menstrual blood • -can be conserved by the kidney for reabsorption

8. -unabsorbed copper is in the feces • -in high levels, zinc can induce copper deficiency by stimulating intestinal cells to produce more metallothionein which binds copper more avidly than zinc and then is exfoliated with the intestinal cells • -fiber and phytate do not adversely effect copper absorption

9. RDA and Sources • -see handout

10. Deficiency • -decrease in serum copper and ceruloplasmin levels are seen • -neutropenia, leukopenia,bone demineralization • -subperiosteal hemorrhages, hair and skin depigmentation, defective elastin formation • -failure of erythropoiesis, cerebral and cerebellar degeneration>>>death

11. -neutropenia, leukopenia are the best early indicators in children • -because it is stored in the liver, deficiency takes a long time to develop • -bone changes such as osteoporosis, soft tissue calcification can occur with prolonged TPN

12. Menke’s disease • -sex-linked recessive defect that results in copper malabsorption, increased urinary loss, and abnormal intracellular copper distribution • -affected infants: retarded growth, defective keratinization and pigmentation of hair, hypothermia, degenerative changes of the aorta, mental deterioration, abnormalities of the metaphyses of long bones • -all of the above is due to interference with collagen and elastin cross-linking

13. Menke’s cont’d • -there is accumulation of copper in the intestinal mucosa even though copper and ceruloplasmin levels are very low • -transient improvement with parenteral copper

14. -***decreased plasma copper levels are also seen in malabsorptive diseases, celiac sprue, tropical sprue, protein-losing enteropathies, and nephrotic syndrome

15. Toxicity • -increased copper levels seen during pregnancy and in women on OCP’s, those with acute and chronic infections, pts with liver disease • -***any liver disease that interferes with bile excretion (primary biliary cirrhosis) and mechanical obstruction causes increases in liver copper • -***Wilson’s disease: accumulation of excessive copper in the body tissue as the result of a genetic deficiency in the liver synthesis of ceruloplasmin

16. Iodine • -body normally has 20-30 mg of iodine and more than 75% is in the thyroid gland • -the rest is in the mammary gland, gastric mucosa, and blood • -it’s only function is related to thyroid hormone

17. Absorption and Excretion • -iodine is absorbed in the form of iodide • -occurs both as free and protein-bound iodine in circulation • -iodine is stored in the thyroid where it is used for the synthesis of T3 and T4 • -the hormone is degraded in target cells and in the liver and the iodine is conserved if needed • -excretion is primarily via urine • -small amts from bile are excreted in the feces

18. Deficiency • -goiter—enlargement of the thyroid gland • -deficiency may be absolute—in areas of deficiency, or relative—adolescence, pregnancy, lactation • -goiters are more prevalent in women and with increased age

19. -goitrogens occurring naturally in foods can cause goiter by blocking absorption or utilization of iodine (cabbage, turnips, peanuts, soybeans) • -***severe deficiency during gestation and early postnatal growth: cretinism—mental deficiency, spastic diplegia, quadriplegia, deaf mutism, dysarthria, shuffling gait, short stature, hypothyroidism

20. Toxicity • -iodine has wide margin of safety • -goiter usually occurs with excess intake>need

21. Chromium--Functions -required for normal lipid and CHO metabolism and for the fxn of insulin -?can supplementation raise HDL

22. Absorption and Excretion • -10-25% absorption in its trivalent form • -amount absorbed remains constant at dietary intakes >40 ug (micrograms) at which point excretion in urine is proportional to intake • -increased intake of simple sugar, strenuous exercise, or physical trauma also increase urinary excretion • -both chromium and Fe are carried by Tf, however albumin can also assume this role

23. Deficiency • -altered CHO metabolism, impaired glucose tolerance, glycosuria, fasting hyperglycemia, increased insulin levels and decreased insulin binding • -impaired growth, peripheral neuropathy, negative nitrogen balance • -increased chromium losses in stress • -hyperglycemia and wt loss reverse with IV supplementation in TPN

24. Cobalt • -most stored with vitamin B12 • -component of B12—cobalamin • -essential for maturation of RBC’s and normal function of all cells

25. Absorption and Excretion • -shared with Fe • -absorption is increased in pts with deficient Fe intake, portal cirrhosis with Fe overload, and hemochromatosis • -excretion is mainly thru the urine • -small amts in feces, hair, sweat

26. Sources and Intakes • -microorganisms are able to synthesize B12 • -***humans must obtain B12 and cobalt from animal foods such as organ and muscle meat • -***takes a long time to become deficient—happens in vegetarians

27. Deficiency • -related to vit B12 deficiency • -**macrocytic anemia • -genetic defect: pernicious anemia • -tx: massive doses • -more in the vitamin lecture

28. Toxicity • -polycythemia • -hyperplasia of BM • -reticulocytosis • -increased blood volume

29. Selenium • -glutathione peroxidase • -acts with other antioxidants and free radical scavengers • -overlaps with vit E for antioxidant effects • -fxn with vit E to protect cell and organelle membranes from oxidative damage

30. Absorption and Excretion • -upper segment of the small intestine • -increased absorption with deficiency • -status is measured by measuring selenium or glutathione peroxidase in plasma, platelets, and RBC’s or selenium levels in whole blood or urine • -RBC selenium is an indicator of long-term status

31. Deficiency • -rare • -Keshan Dz or Kashin-Beck Dz • -long term TPN, cancer, CF

32. Molybendum • -relationship with copper and sulfate • -cofactor of many enzymes involved in the catabolism of sulfur AA, purines and pyridines • -Toxicity: gout-like syndrome, reproductive SE’s • -Deficiency: increased risk with co-existing copper deficiency, TPN

33. Silicon, Vanadium, Arsenic, Boron • -see handouts • -will not be on the exam!!!