Consequences of Mineral and

Deficiencies
Part I

KEY FACTORS IN MINERAL RESERACH

Rule: There is no stronger evidence of a minerals 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

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

Typical Signs of Mineral Deficiencies

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

Potassium

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

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.

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
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

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

Iron
and
Anemia

Fe

1. 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

Fe

Anemia and pregnancy

Rule: Pregnant women have double the adult requirement

Fe

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

Fe
Fe

Mineral Composition of Mammalian Milk

Rat
Mg/Liter
Calcium
Sodium
Potassium
Iron
Copper
Zinc
Manganese

5645 879
1228 126
2669 429
15 2
72
29 6
979 363

after
Reichlmayr-Lais and Kirchgessner
When it comes to minerals, milk
is far from being natures
perfect food
After Picciano

Human

Bovine

Mg/Liter
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

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 and Skin Rash

Zn

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 middleaged 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

Zn
Zn

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 30mg 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 30mg/d on one measure of
spatial working memory and a detrimental effect of 15mg/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

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

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 antiinflammatory 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 perfume 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.