Nutrition topic Patommatat MD Zinc Chromium Copper.

Nutrition topic

Patommatat MD

Zinc

Chromium

Copper

What is Zinc ?

• Chemical element• Atomic number 30• Zn2+ = common oxidation

state

Zinc

Biochemical and physiological function

300 Human enzymes

Example :

RNA polymerase I,II,III

ALP

Carbonic anhydrase

ApometalloenzymeZn

Zinc Metalloenzyme

1. Catalytic function

Biochemical and physiological function

Cause Protein folding Example :

Zinc finger motif Loss Zinc

alter protein folding

Loss of protein function

2. Structural function

Biochemical and physiological function

Gene responsiveness Receptor-mediated signal

transduction Antigen-dependent T-cell fn

3. Regulatory function

Transcription factor “Zif268”

DNA

Zn

Zinc excretion

• Sloughing of mucosal cells• Pancreatic secretion• Trans-epithelial flux

1. GI 2. urine

• 1 mg/d in normal• Increased with muscle protein

catabolism Zn bound with amino acid pass kidney filter3. Others

• Integument 1mg/d• Menstruation 0.1-0.5mg total• Semen 1mg/ejaculation• Parturition 100mg/fetus & placenta• Lactation 2.2mg/d at wk 4

0.9mg/d at wk 35

Zinc turnover

• Recycling by Erythron• 20-40 μgZn/gHb• 750 g in adult Hb• Turnover of Zn pool

0.12 - 0.25 mg/d

How can we loss Zinc ?• Absorption

– Diarrhea– Pancreatic

insufficiency– Inflammatory bowel

diseases

• Protein catabolism– Stress / sepsis– Nephrotic syndrome

• Skin loss – burn, pemphigus, EM

• Increased requirement– Pregnancy– Lactation– Infant, children,

Adolescence

• Prolonged intake of High phytate diet

• Not taking Zinc containing diet : TPN

• Peritoneal dialysis

Other condition • Alcoholism hyperzincuria• DM• Infection• Zn chelator : penicillamine

Phytate • principal storage form of phosphorus in many plant tissues, especially bran and seeds

• strong chelator of important minerals such as calcium, magnesium, iron and zinc

• contribute to mineral deficiencies in developing countries

Food source

• Organ & flesh

High Zn No phytate• Egg & Dairy food

Low Zn No phytate• Cereal & legumes

Low Zn High phytate

Zinc deficiency : How to identify?• Clinical setting

– Low dietary intake– Risk people : Alcohol, High prot. catabolism

• Clinical sign– Dermatitis– Defect in immune function– Growth retardation & Delayed sexual

maturation

• Functional response to supplemental Zn

No lab can completely identify !!

Acrodermatitis enteropathica

Erythematous patch with crusted vesicles

Role of Zinc in Nutritional support• Burn patient• Supplement in zinc def patient

How we replace zinc ?1.Oral replacement : Zinc acetate solution• Dose : 5-10 ml oral bid

2.TPN : Addamel N• Zinc 6.5 mg/10ml (100μmol)

• Chemical element• Atomic number 29• Cu2+ common

oxidative state

What is Copper ?

Copper

Copper Biochemistry

• Cu-containing enzyme• Cu-binding protein• Low molecular wt. ligands

– Histidine, Cystine, Glutamine, Threonine– Peptides

Important Copper containing enzyme

• Lysyl oxidase Cross-link Elastin and collagen fiber

• Feroxidase I = Ceruloplasmin Transfer Iron from storage site to Hb synthetic site

• Cytochrome C oxidase generate ATP• Superoxide dismutase(SOD) Free radical

scavenger prevention of cell damage• Tyrosinase melanin synthesis

Copper binding protein

• Metallothionine: Metal storage in liver• Albumin : Prevent intravascular toxicity• Transcuprein : Role may be a transportor• Factor V, VIII : Role not known

Physiologic function• Connective tissue formation• Iron metabolism & erythropoiesis• Myelin formation (Required ATP)• Neurotransmitter: NE,DA,E• Melanin formation:

Albinism if defect

Copper in diet

Absorbed through intestinal mucosa 2%

Remaining

unabsorbed Cu 98%Liver

Tissues

skin hair

Intes tract

ceruloplasmin

Delivery Cu to

Peripheral tissues Secrete Endogenous Cu

FecesAlbumin

LMW ligands

Portal v. by Albumin, Transcuprein, LMW ligands

Copper Elimination

Extra-gastrointestinal route

Cu2+

Cu2+

Copper route

In human body

Bile

kidney

Risk of Copper deficiency• Increased GI loss : Diarrhea, fistula• TPN• Prolonged antacid use• High dose Zinc supplementation: sickle cell• Severe handicapped Patient• Cystic fibrosis• Infant : Premature Breast fed, Chr. PD

Copper deficiency• Anemia : Hypochromic normocytic• Osteoporosis in growing bone• Neutropenia• Other not well established:

– Arthritis– Depigmentation– Myocardial disease– Neurologic effect demyelination

Food source

• Rich source• Intermediate source• Low amount

• Shellfish• Nuts• Seeds• Legumes• Liver • Organ meat• Bran & germ portion of grains

Recommendation

• Recommended dietary allowance (RDA)

0.9 mg/d• Tolerable upper intake level (UL)

10 mg/d• Pregnancy RDA= 1 mg/d• Lactation RDA= 1.3 mg/d

Copper toxicity• Copper excess from metallothionine in liver

begin to damage liver and other tissue– Liver– CNS

• High serum free copper• Low serum ceruloplasmin

Conclusion : point in clinical practice• Copper deficiency found in Prolonged NPO

Pt with NON – Copper added TPN• Beware copper supplement in cholestasis

liver disease copper toxicity

What is Chromium ?

• Chemical element• Atomic number 24• 2 common form

– Trivalent form (CrIII)– Hexavalent form (CrVI)

Chromium

Nicotinate

Picolinate

Cr(III)

Bind with ligands

Cr(VI)

Acetate

Gastric acid

Strong oxidizing

agent

(Chromate & Dichromate)

Irritating & potential hazard

Food

Chromium picolinate

Biologic Activity• Glucose homeostasis• Lipid profile• May be good for osteoporosis

History• Discovery of Glucose tolerance

factor (GTF) in yeast ; 1929• Rats fed with Torula yeast-based

diet began to show signs of glucose intolerance• Reversed by a diet of brewers yeast

Mertz W, Schwarz K. Relation of glucose tolerance factor to impaired intravenous glucose tolerance of rats on stock diets. Am J Physiol 1959;196:614-618.Schwartz K, Mertz W. A glucose tolerance factor and its differentiation from factor 3. Arch Biochem Biophys 1957;72:515-518.

Benefit Even in Healthy• 200 mcg/d Cr picolinate in healthy subjects

for 7 wks– Decreased FBG 8%– Increased Fasting insulin significantly 28%

Diabetics• 200 mcg/d Cr picolinate in hyperglycemic

subjects for 3 mos– Lower glucose level– Lower insulin use – Improve glucose tolerance

People with high risk• 1000 mcg/d Cr picolinate in people with

obesity and FH of DM type 2 for 8 mos– Increased Insulin enhanced Glucose

clearance increased Ins sensitivity– Inhibition of Hepatic glucose production

Cefalu WT, Bell-Farrow AD, Stegner J, et al.Effect of chromium picolinate on insulinsensitivity in vivo. J Trace Elem Exp Med1999;12:71-83.

Benefit on Hypoglycemia ALSO !!• Placebo-controlled crossover trial• 200 mcg/d CrCl3 for 3 mos• Alleviating symptoms of Hypoglycemia• Raising minimum Glucose level 2-4 hr after

glucose challenge

Anderson RA, Polansky MM, Bryden NA, et al. Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia. Metabolism 1987;36:351-355.

Glucose homeostasis : In view of Glucose/Insulin Axis

Normal person DiabetesHypoglycemiaLow G/I ratio High G/I ratioBalance G/I ratio

Balance G/I ratio

[chromium deficient state]

[After chromium supplementation]

Glucose tolerance factorUse to define Organic chromium degradation product from yeast

Low molecular- weight chromium binding substance (LMWCr)

Found in Mammalian tissue Many ways similar to GTF Composed of : cysteine, glutamate, aspartate, Glycine store in cytosol of insulin-sensitive cell Stimulation of tyrosine kinase activity insulin

signalling

Insulin Receptor

Tyrosine kinase protein receptor

Low molecular weight Chromium

Factor influencing Cr absorption

• Chromium extent in diet • Ascorbic acid enhanced Cr absorption• Other metal def state Zn or Fe def • Antacids Decreased Cr absorption• ASA & Indometacin enhanced Cr absorption

Chromium Deficiency• 2 Case reports ; both on non-Cr addd TPN• Symptoms

– Severe hyperglycemia– Rapid wt. loss– Decreased RQ (increased fat utilization)

Adequate intake

Age (yr) Female (μg/d) Male (μg/d)

19-50 35 25

≥ 51 30 20

Food source• All food supply in small amount• More in whole grain & cereals• Refined sugar < less refined product• High Cr in processed meat• Acidic food received Cr from stainless steel packing !!

Free radical generationBy Chromium(III) picolinate

Mutagenic effect !!

Adverse effect of Chromium

Steams D M, Wise J P Sr, Patiemo Sr, Wetterhahn K E. Chromium (III) picolinate produces chromosome damage in Chinese hamster ovary cells. FASEB J 1995; 9: 1643-1648.

Wrong use of chromium !!• Losing weight agents• Muscle building agent• No study shown benefit !!

Conclusion : point in clinical practice

• Chromium may be used as alternative Rx in DM need further study

• Chromium deficiency is seen in Prolonged use of Non-Chromium added TPN