Metabolisme

Mikro Mineral

1
Mikromineral
Elemen yang tersusun sekitar 0.8% (0.01
– 0.00001%) dari berat badan tubuh,
diperlukan dalam jumlah sedikit tetapi
esensial untuk seluruh proses
metabolisme tubuh.

Zn, Cu, Se, Fe, I, Mn, Cr, …

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Peranan mikronutrien dalam metabolisme
Respirasi di mitokondria
& sintesa ATP
Immune function: Komponen Hb, mioglobin,
chemotaxis, phagocytosis sitokrom (P450, a,b,c)
of neutrophils and Sitokrom oxidase
monocytes Enzymes involved in DNA,
cytotoxic lymphocyte and
RNA and protein synthesis
NK cell activity
Bone formation and
Neuromuscular, muscle,
cardiovascular function,
Micronutrien mineralization
Synaptic transmission Zn, Cu, Se, Fe, Antioxidant defence
proteins, hormons Cu/Zn SOD, GSH-peroxidase
I... DNA repair enzyme
Components of metallothioneins
Detoxyfication of heavy
metals and xenobiotics Involved in food catabolizm
Thyroid function:
Thioredoxin reductase
Iodothyronine Lowe NM et al. 2002,
deiodinase Erickson KL et al. 2000, Ames BN Mutat
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Res 2001, Hartwig A. Mutat Res 2001
Miconutrient
 Optimum intake dapat bervariasi, tergantung:
– Umur
– Jenis kelamin
– Faktor genetik
– Kondisi kesehatan
– Influences by other aspects of diet, dietary practices
– Geographic differences (mineral content in soil, water etc.)
 Recommended intake established for general
healthy population
– The Recommended Daily Allowances (RDA) have been set at
levels that prevent deficiency for 95% healthy people
– Dietary Reference Intake (DRI)/ Estimated Average
Requirement (EAR)– nutrient intake meeting requirement
levels for 50% of the healthy subjects

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National recommended nutrient intakes for
the elderly

Hartwig A. Mutat Res 2001

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Antacids - ↓ absorption of
Zn, Fe, Ca, Mg Physiological Decresed energy and general
Diuretcs - ↑ loss of Mg, Zn, modification nutrients intake,
Ca, Na, K, Cl occuring Sensory and gastrointestinal
Tetracyclines malabsorption in the lifetime tract changes
of Ca, Fe, Mg, Zn Declining renal function - ↑
Laxatives – loss of Zn, Ca, loss
Mg

High levels of
Micronutrients Presence of chronic
medication use: reason for diseases affected
mineral-drug different absorption and
interaction needs bioavailability
in the elderly

Ingestion of restricted diets, Atrophic gastritis,

Loss of appetite, Loneliness, Gastrointestinal
Depression, Functional malabsorption,
disability, Low socio-
Environmental
Renal dysfunction
economic status, Long-term influences
hospitalization, Parenteral ↓ Richard MJ et al. Proc Nutr Soc 1999
Decreased intake Polidori MC J Postgrad Med 2003
nutrition Thomas JA Nutr Rev 1995 6
 Anorexia, Impaired wound
weight loss Depression, mood lability, healing - Zn
Cognitive deficits
Zn, Fe, Mg
Bone loss;
Anaemia (Fe, Cu)
Zn, Cu, Mg, Ca

Hormonal disorders Micronutrient Myopathy (Mg, Se)

deficiency
Oxidative stress Impaired immune function:
Oxidative damage to DNA, proteins
↓chemotaxis, phagocytosis and bactericidal
↓ SOD, ↓ GSH-Px
fuction of monocytes and neutrophils;
DNA repair enzyme deficiencies
↓ lymphocyte proliferation;
↓ cytotoxic lymphocyte and NK cell activity
Se, Zn, Cu, Fe
Accelerated ageing
↑ sensitivity to repefusion injury ↑ mutaions and
↑ incidence of cardiovascular diseases: carcinogenesis ↑ susceptibility to
CHD, hypertension, CHF ↓
Alzheimer, Parkinson disease, infections
cancers
cataract, arthritis 7
Richard MJ, Roussel AM Proc Nutr Soc 1999
Micronutrient deficiency in the elderly

Generally secondary to low energy

intake and undernutrition
Particulary affects hospitalized,
institutionalized and frail elderly
Acute/severe deficiencies are rare,
common moderate or slight - contribute
to poor well-being, and many chronic
conditions

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Selenium and cancer deaths
adjusted odds ratio (Kornitzer M. Eur J Clin Nutr 2004)

Serum Se Cases 139♂ Controls ♂ Cases 50 ♀ Controls ♀

OR (95%CI) 400; p (95%CI) 145; p

≤ 72μg/ml 2.2 (1.3-3.7) 0.018 0.7 (0.3 – 1.6) 0.589

73 – 84 1.7 (1.0 – 2.8) 0.7 (0.3 – 1.5)

μg/ml
≥ 85μg/ml 1.0 1

Increased risk of cancer (♂): prostate, lung, colorectal,

stomach, pancreas, breast, thyroid, bladder
(Kornitzer et al. 2004)
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Selenium and cancer
Clark LC at al. JAMA 1996 - 200μg Se
% 0

-10

-20

-30
-37
-40
-44
-50 -50

-60 -61
-65
-70
Total ca Total ca Lung ca Prostatae ca Colorectal ca
mortality incidence incidence incidence incidence
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Minerals significance
Serum Se inversly correlated with
homocysteine concentration
(Gonzales S et al. 2004)
 Low serum selenium – enhanced production
of TXA2, decreased production of PGI2
(Alissa EM et al. 2003)

Two years supplementation Cu 5 mg, Zn

15 mg,Ca 1000 mg, Mn 2.5 mg reduced
bone loss and increased bone density of
+ 1.28 compared with placebo, p=0.036;
(only Ca - -0,5)
(Saltman, Strause 1993)
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Zn/Se significance -2 year supplementation
study Girodon F et al. Ann Nutr Metab 1997, 41, 98
Placebo Zn 20 mg, Se 100 μg Vitamins Trace element
+ Vitamins
n 20 20 20 21
Total deaths 7 6 5 7
Deaths from 2 0 0 1
infections
Infections 1 y 16 7 10 14
Infections 2 y 19 5 14 9
Total 35 12 24 23
infections
Mean 1.75± 0.6 ± 0.99 1.2 1.09 ± 1.09
number of ±1.43
infections 1.48
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Free-Living Senior Volunteers n = 1740 in Arizona
EAR – Estimated Average Requirment
(Foote JA et al. J Am Coll Nutr 2000)
Mineral/age Mean Dietary Intake Intake<100% of EAR
Men Women Men (%) Women(%)
Calcium
51 - 71 yr. 875.4±14.05 814.5 ±25.07 82.7 84.6
71 – 85 yr. 851.6 ±26.34 814.4 ± 61.52 83.8 88.8
Magnesium
51 - 71 yr. 344.8 ± 3.98 329.9 ± 7.48 56.5 38.1
71 – 85 yr. 347.6 ± 7.86 326.2 ± 14.29 55.3 37.1
Iron
51 - 71 yr. 14.3 ± 0.18 11.4 ± 0.25 3.0a 9.8a
71 – 85 yr. 13.8 ± 0.35 11.1 ± 0.46 3.8a 10.1a
Zinc
51 - 71 yr. 11.3 ± 0.14 10.0 ± 0.21 42.6a 35.2a
71 – 85 yr. 11.7 ± 0.32 10.1 ± 0.49 41.7a 39.3a
Copper
51 - 71 yr. 1.5 ± 0.02 1.4 ± 0.04 22.8a 29.1a
71 – 85 yr. 1.5 ± 0.04 1.5 ± 0.07 22.2a 24.7a

a – recomemnded levels are 2/3 of the RDA 13

Trace element intakes in the elderly

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Requirements for trace elements
in the elderly

Richard, Roussel Proc Nutr Soc 1999, 58, 573.

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Micronutrient excess

Copper - prooxidant
Zinc – impaired immune function,
decreased bioavailability of Fe, Cu
(Chandra RK 1992, 2004, Nakamura et al. 1987)
Selenium – oxidative damage
Iron excess lead to DNA oxidative
damage, carcinogenesis (Nelson 1994) and
heart disease (Ascherio et al. 1994), Alzheimer
disease (Smith et al. 1997), low Cu and Zn
status
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 Micronutrient deficiency in elderly -
summary.
 Susceptibility due to a triad:
ageing/chronic conditions &medications/environment
 Impairs:
– Immune system (increased incidence of infections!)
– Oxidative defense (promote chronic diseases)
– WELL-BEING (unfavourable)
 Warrants actions
– Reference for dietary intake in elderly to be established
– Education to increase awareness (patient/family/physician)
– Proper intake/elderly at risk.
 Supplementation indicated ONLY in deficient patients
(improved immune defense, reduced risk of age-
related diseases). EXCESS has deleterious effect. (like
elsewhere in life). 17
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 Micronutrients in the elderly
 Relationship between age and micronutrient status:
– Iron
• Fe requirement in older subjects is lower, Fe deficiency is rare
(Richard MJ 1999)
• 4-year follow-up in group of healthy elderly in France – average Fe
intake higher than recommended (Nicolas AS et al. 2000).
– Zinc
• inverse correlation between plasma Zn and age (Hercberg et al.
1991)
• Zinc deficits are more related to hospitalization and chronic
diseases than to age; Zn – 38% below RDI (Schmuck et al. 1996)
– Copper
• Status not modified by aging process (Richard MJ 1999)
– Selenium
• Status not modified by aging till age of 75 y. then lowered (Neve
1989, Olivieri 1994)

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Selenium and cardiovascular diseases
 Suggested threshold effect < 45 µg/l – assotiation
between serum Se and cardiovascular diseases
 Data from studies inconsistent:
– Salonen et al. 1982 -Se<45 µg/l - RR 2.9 from CHD, 2.1 from MI
– Miettinen et al. 1983 - Se 50-105 µg/l - no sigificant risk
– Virtamo et al. 1985 - Se< 45 µg/l – RR 1.4 from CHD, from
cerebrovascular diseases
– Ringstad et al. 1986 -Se 59 – 197 µg/l – no sigificant risk
– Kok et al. 1987 -Se< 105 µg/l - RR 1.1 from CHD, – stroke
– Suadiciani et al. 1992 - Se< 79 µg/l RR 1.6 from CHD
– Salvini et al. 1995 - Se>80 µg/l - no sigificant risk
– Kardinnal et al. 1997 - Se toenail 0.55ug/gm RR 0.63 from MI

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Multinutrient supplementation - 1 year
(Chandra RK Lancet 1992, 340,1124

p = 0.002
days 50 48
45
40 p = 0.004
35 32
30
25 23 supplemented
20 18 controls
15
10
5
0
days of infection days with antibiotics

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Estimates of the percentage of individuals who do not
consume 100% of the dietary reference intake of Mg
and the recommended daily allowance for Zn
90%
80%
70%
60%
50% 50-59
40% 60-69
>70
30%
20%
10%
0%
Men Women Men Woman
Magnesium Zinc
Adapted from the US Department of Agriculture Continuing Survey of
Food Intakes by Individuals 22
 Trace element intakes in polish free-living
and hospitalized elderly
Minerals Women In Men In
hospital hospital
mg/d RDI Mean % RDI Mean RDI Mean % RDI Mean

Ca 1000 620 62 385.3 800 422 52.7 510

Mg 280 185 62 162 350 204 58.3 225

Fe 12 11 91,7 6.3 11 10 91 8.25

Zn 10 8.51 85 6.01 14 7.94 57 7.72

Cu 2.0-2.5 0.91 45.5 0.71 2.0-2.5 1.12 56 0.97

Mn - 3.8 - 1.98 - 3.54 - 2.61

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Gabrowska E. 2004