IRON OVERLOAD -
THE MISSED DIAGNOSIS
by:
Cutler, Paul, M.D.
Dr. Cutler graduated from the University of
Toronto medical school, and practiced nutritional and general
medicine in Toronto until 1993. He has clinics now in St. Catharines,
Ontario and Niagara Falls, New York. He has published many research
articles on excess iron in medical journals including Diabetes (Oct.
1989), American Journal of Psychiatry (Jan. 1991), Journal of
Neurological and Orthopaedic Medicine and Surgery (Spring 1993), and
Canadian Journal of Psychiatry (Feb. 1994).
My interest in iron metabolism began around
1986 when I read an article published in The Mayo Clinic
Proceedings by Virgil Fairbanks who was then chief of iron
metabolism. His article, Hemochromatosis or Iron Overload - the
Neglected Diagnosis was a scathing attack on the medical
profession for ignoring excess iron in the body. Physicians were
more interested in anaemias and low iron deficiency and did not
really perform the necessary tests of iron metabolism to diagnose
the opposite end of the spectrum - iron overload. He described
conditions directly related to excess iron in the body such as
arthritis, diabetes, psychiatric illness, and liver disease.
These conditions were very common in my
medical practice, and I decided to find out how many of my patients
had excess iron, and it turned out to be a significant number, as
many as 30% of my patients. When I began to lower the iron levels,
my patients improved, and I published some research articles on the
subject in some rather prestigious medical journals. By 1989,
doctors began publishing research which showed that iron was also a
risk factor in cancer at levels that were far less than what
they had thought safe in the past. In September 1992, a classic
article in Circulation by Jerome Sullivan showed that excess
iron was also a risk factor in heart disease, second only to
cigarette smoking as a cause of heart attacks in men. Sullivan's
study sent shock waves through the medical and nutritional
communities because doctors have been prescribing supplementary
iron, and nutritionists have been insisting that food be fortified
with iron, and this was a reminder that excess iron is very
dangerous. In the following year, studies were published which
showed that vitamin E and vitamin C reduced the rates of heart
attacks and angina, and when you put all of these studies together,
you realize that iron is capable of inducing free radical or
oxidative pathology.
EFFECT OF EXCESS IRON ON ANTIOXIDANTS
Two thirds of the iron in the body is in the
hemoglobin itself where it is believed to be safe, about 6% in
muscle and various important iron enzymes, and 27 to 30% in storage
and this has now been shown to be no longer safe but it will
overwhelm the cells and cause free radical pathology. Free radicals
are normally produced in the body for metabolism of oxygen, but free
radicals can also be produced by excess ultra violet radiation,
excess sunlight, tobacco smoke, and an excess of any metals such as
iron or copper and they can deplete the antioxidants such as
vitamin C and E in the body. Free radicals are atoms with an
unpaired or an extra electron in any orbit, usually the outer one.
The free radicals create havoc to normal cells by removing electrons
from the normal cells to pair their own missing electron, and this
damages the healthy cell which in turn tries to draw electrons from
an adjacent cell, and this chain reaction of destruction will
continue, unless there are enough antioxidants to step in and donate
electrons to these cells or to the free radicals and stop the
attack. So as the iron builds up, the antioxidants go down.
Therefore in order to offset the adverse affects of excess iron, you
need adequate supplies of the antioxidants vitamin C, vitamin E, and
beta carotene, often in amounts much larger than the average
balanced diet can supply.
CANCER
Tumour cells and bacteria need iron to grow,
and your body tries to starve them of iron by diverting the iron
from the blood to storage sites deep within the tissues. It is well
known, biochemically, that if you add iron to tumour cells in
cultures, they grow at a much faster rate and that breast cancer
cells thrive on iron. In 1988, many studies began to surface showing
that iron was indeed a risk in common cancers such as lung, colon,
bladder, oesophagus, and at levels that were shockingly less than
doctors had previously considered dangerous. A study in the New
England Journal of Medicine (Oct. 1988) by Dr. Richard Stevens
showed that as iron saturation levels increase, cancer rates go up.
Until that time a 65% saturation level was considered to be safe,
but this study showed that at a 37% saturation level, the cancer
rate started to skyrocket, and doctors began to question the levels
they had previously considered safe. In January 1994, in the
International Journal of Cancer, Dr. Stevens reported that cancer
rates were increasing at levels of only 31%.
ATHEROSCLEROSIS
Some interesting findings came out of the 1992
Sullivan study. Many doctors began reporting that as iron levels
increase, as ferritin goes up above 200, the cholesterol levels also
go up, especially the LDL (bad) cholesterol, regardless of changes
in diet such as reducing high cholesterol foods. Blood sugar goes
up, blood pressure goes up, triglycerides go up and HDL levels go
down. Despite all the recent studies in cardiology and
cardiovascular surgery journals, I still don't know of any
cardiovascular surgeons who put their patients on vitamin E or
attempt to remove excess iron before they do these procedures.
Doctors don't seem to want to recommend nutritional supplements.
Under 5% recommend vitamin E to heart patients. It's tragic, because
they know better.
FATIGUE
The most common symptom of iron overload is
weakness, lethargy and a fatigue that is disabling. As the iron
builds up it disturbs other body processes and depletes certain
minerals and vitamins such as zinc, and vitamin E and vitamin C.
CIRRHOSIS OF THE LIVER
Abdominal pain is the next most common symptom
and this is usually in the right upper quadrant because the liver is
involved. In iron overload patients, cirrhosis of the liver is 13
times more common than in the general population.
ARTHRITIS
Arthritis caused by iron is common in anywhere
from 35 to 60% of people who have arthritis, especially in young
people, and it will start with the first three fingers, or the
knuckle joints of the thumb, index and third fingers; although any
joints can be involved, these will get the brunt of it.
ENDOCRINE IMBALANCE: THYROID, ADRENALS,
DIABETES
Iron has a marked affinity for the different
glands. One of the first glands that is affected is the pituitary,
and it is common to find evidence of low pituitary hormones.
Testosterone production in the testicles is reduced and this can
cause impotence. Iron can also affect the thyroid, and the adrenal
glands and will eventually affect all tissues if untreated, but
endocrine tissues are the most effected. And the most common
endocrine manifestation is diabetes.
PSYCHIATRIC DISORDERS
If the iron is not needed by the bone marrow
to make new red cells, then it goes to tissues like the liver. The
next major source for storage of iron is the brain. Iron affects the
neurotransmitters in the brain, affecting the hydroxylase system in
the brain, so that psychiatric symptoms and neurological symptoms
like confusional states, dizziness, mood disorders, and even ringing
in the ears are relatively common.
ALZHEIMER'S DISEASE
Dr. Richardson, Chief of Psychiatry at the
University of Saskatchewan feels the major cause of Alzheimer's
Disease is excess brain iron levels. So as liver iron builds up,
brain iron levels build up. Dr. McLachlan at the University of
Toronto Dementia Clinic showed that aluminum was the cause of
Alzheimer's Disease (D.R.C. McLachlan et al. Desferroxamine.
Lancet, June 1991). He is using an iron chelator called
deferoxamine to treat Alzheimer's Disease and his results are
probably better than any other treatment program for Alzheimer's. He
stated that the drug arrests the disease. Dr. Richardson and Dr.
McLachlan have been arguing, "Is it the iron, or is it the
aluminum?" The same medication lowered both. It is my feeling that
iron is a far greater risk in this condition than is aluminum.
PIGMENTATION
Iron overload has often been called the
"bronze disease", because untreated people can develop this natural
beautiful tan without going out in the sun, but that is an end stage
and we don't see that any more. However, you will see isolated
patches of brown that almost look like coffee stains on the skin.
These clear up dramatically and the bronzing goes away as the iron
is removed.
CAUSES OF IRON OVERLOAD
HEREDITARY
Hereditary hemochromatosis is a genetic
disease in which abnormal genes permit the individual to absorb too
much iron from an ordinary diet. This hereditary factor is probably
the most common way people get overloaded with iron. There is no
real mechanism for controlling iron absorption in the body. Outside
of menstruation, the body really has no way of getting rid of extra
iron. Normally the average diet contains 15 to 25 mg. of iron and
yet all we need is one mg. per day for normal metabolism. In
hemochromatosis, 3 or 4 mg. of iron per day are absorbed instead of
the 1 mg. we need, and over the years this results in massive
overloading and accumulation of iron in the vital organs. As many as
20% of the population has the genetic potential to overload with
iron from what we would call a normal dietary intake. Jerome
Sullivan who has published papers on iron as a cause of heart
disease since 1981 believes that hereditary hemochromatosis is
basically the reason some families have a greatly increased risk of
heart disease.
TRANSFUSIONS
Certain anemias require a lot of transfusions
and patients can be overloaded with iron in this way.
SUPPLEMENTS
If you take iron supplements over an extended
period of time when you don't need them, you will overload with
iron. Many in the medical profession have been guilty of abusing
prescription of iron supplements without even performing iron blood
studies because they felt iron was safe. Also, people who have too
much iron can get very sick from taking vitamin C and must use
vitamin C carefully because it increases iron absorption especially
when taken during or after meals.
NUTRITIONAL INTAKE
There are sources of nutritional dietary iron
which raise the iron levels in the body such as red meat and
alcohol. Iron exists in two forms and this is important to
remember because they are absorbed differently. The heme iron, meat
iron or ferrous iron has probably around 12 to 15%
absorption, whereas the non-heme, ferric or plant iron has
only 2 to 5% absorption. This is why the studies by Sullivan and
others have shown that it is the red meat iron that really has to be
restricted in diets for people with iron overload, and plant iron is
not considered to be a major offender in iron overload states. Iron
fortified enriched foods can raise iron levels and are now
being questioned. Water with excessive iron levels can cause
something called Kachung's Disease, a disease reported in China,
which is an arthritis and heart disease from excess iron. There is
the classic Bantu disease occurring in Bantus who brewed beer in
pots that are excessively high in iron. Iron cooking utensils
can increase the iron content in the food from 3 to 10 fold. This is
especially true of acidic foods such as tomato sauce. Alcohol
per se is not high in iron, but it's a potent reducing agent and
reducing agents can convert the ferric from plant iron to the
ferrous or heme iron, and will increase the absorption of iron from
the intestine.
SCREENING FOR EXCESS IRON
There are four necessary tests:
serum iron, TIBC (total iron binding capacity), percent transferrin
saturation and serum ferritin. Acceptable transferrin saturation
was previously 60%; it is now less than 30%. The safe level of
stored iron, called ferritin, was previously 500; after Sullivan's
1992 study, most people accept 120 as normal and 200 as being
significantly toxic. So now we have figures which are about half of
what was considered safe only a year or two ago.
TREATMENT
Dr. Fairbanks at the Mayo Clinic said that
conditions that are related to iron will often be completely cured
when the iron is removed, and scientists are now doing research to
show that you can reverse all of these problems which increase with
iron overload by drawing the blood or lowering the iron. Excess iron
is toxic and it doesn't matter whether your excess iron is genetic
or acquired, it has to be removed. Most iron related problems seem
to occur in men in their late 40's around 49 to 55, and in women
around 60 to 65. The accepted treatment for most people is by
removal of blood. If you draw out the blood, the iron comes out
with it. Most of the time we do it once per week for around 15 to 20
blood removals. We do the same as the Red Cross, we remove 400 or
500 ml. to correct this. 95% of the time we use blood removal or
phlebotomy and 5% we use iron chelators like deferoxamine.
There are certain problems which do not respond to blood letting
such as the type of arthritis caused by iron overload. Chelators are
used in these cases to draw the iron out of the joints and the
arthritis is cured. The Hospital for Sick Children is now
researching an oral iron chelator which may replace all of this but
it will require years of testing.
* * *
For more information see Iron Balance
(1991) by (Harvard Medical School). You may contact the Canadian
Hemochromatosis Society, Box 94303, Richmond, B.C. V6Y 2A6.
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