Minerals and Deficiencies

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
 Key Factors in Mineral Deficiencies

Unlike vitamins mineral deficiency symptoms tend to be ambiguous with the

same symptom appearing for more than one mineral

Many macrominerals have no deficiency signs

Most of the attention in nutrition is on micro-mineral deficiencies

Gejala dan Tanda-Tanda Defisiensi Mineral

Outward Signs Inward Signs

1. Stunted growth 1. Anemia

2. Skin rash 2. Neutrapenia

3. Pigment change 3. Hematocrit

4. Alopecia (hair loss) 4. Impaired digestibility, diarrhea

5. Physical stamina 5. Immune system compromise

6. Skeletal weakness 6. Enzyme dysfunctions

7. Impaired mobility 7. Hormonal dysfunctions

8. Loss of mental acuity 8. Unchecked peroxidations, hypertension

9. Lack of coordination 9. Impaired genetic expression

10. Disease susceptibility 10. Premature aging

 K

Potassium
 Potassium Deficiency K
• 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
 Potassium & Hypertension K
• 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.
 Ca

Calcium
 Deficiency Ca
Ca
• 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
Calcium Deficiency and Bone
Ca
Ca
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.
 Mg
Magnesium
 Mg
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.

Although magnesium deficiency is not likely to occur in

healthy people, it is still be at the root of many clinical
disorders
Deficiency Mg
Mg
 Mg
Causes of Deficiency
• 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
 Fe
Iron
and
Anemia
1. Iron deficiency (50% of the population in some countries)

a. Impairs red cell production

b. Affects general cell growth and differentiation, specifically
Fe
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
 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

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

Early observations Zn
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
 Zn

Zinc
American Journal of Clinical Nutrition, Vol 20, 422-442, 1967
Human Zn Deficiency, Endocrine Manifestations and Response to Treatment
Zn
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

1) Zn deficiency 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.
 Zn
Zn and Skin Rash
Zn and Cognitive Development
Zn
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.
 Harold Sandstead

Zn

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.
James G. Penland
Zn
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.
Effects of Zn supplementation on cognitive function in healthy middle-
Zn
Zn
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.
Zn and Cell Survival Zn
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
 Pamala J. Fraker
Professor
Michigan State University
Zn
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.
 Zn and Malignant Transformation
Zn
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
Zn and the Prostate Gland Zn
Zn
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.
 Zn
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.
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.