IP-6, Iron and Chelation
From The June
2000 Issue of Nutrition Science News
by Bill Sardi
Recent studies reveal that blood donors exhibit lower rates
of many diseases and experience better than average health.
Additionally, the centuries-old practice of bloodletting is
being revived as a treatment for disorders such as heart disease,
cancer and Alzheimer's.1 Why would blood reduction improve
health parameters? In part, because blood removal helps to
control circulating iron levels.
Iron is an essential component of hemoglobin in red blood
cells, is associated with strength, and is required for oxygen
transport, DNA synthesis and other processes. But it also
has a destructive nature. In its free form, unbound from hemoglobin
or other binding proteins, it accelerates oxidation or "rusting"
of body tissues. Since iron-induced oxidation worsens the
course of virtually every disease, iron control could be a
universal approach to disease prevention and therapy.2
Whereas poor iron intake, or impaired absorption, may lead
to anemia, too much iron--iron overload--is even more problematic.3
After full growth is achieved, at about age 18 or so, excess
iron accumulates in the blood of all humans at the rate of
1 mg per day.2 About 80 percent of the body's iron stores
are in the blood. Women are less at risk for iron buildup
than men because of the blood they lose monthly during menstruation.
As a result, women have somewhere around half the circulating
iron levels as men. Their rates for heart disease, cancer
and diabetes are also about half those of males. Because men
have no direct outlet for iron, by age 40 their iron levels
are similar to those of a postmenopausal 70-year-old woman.
This amount of iron can lead to premature aging and diseases
such as arthritis, cancer, cataracts, diabetes, osteoporosis,
and retinal, liver and brain disorders.4 Postmenopausal women,
or women who have undergone early hysterectomy in their 20s,
30s and early 40s, may experience similar problems.5
Recognizing the Problem
Iron overload hasn't gone completely unnoticed. There are
a number of books on the topic, but most are written for health
professionals, leaving the public largely unaware of the problem.
Also, some confusion exists regarding the role of iron in
health and disease. First, there is a mistaken idea that the
majority of the people affected by iron overload diseases
have the genetic form, called hemochromatosis, which affects
only about 1 million of the estimated 275 million Americans.
In fact, the potential threat of iron overload is universal.
It comes with advancing age and regardless of genetic factors.
Second, the emphasis on preventing anemia in children and
menstruating women has detracted attention from progressive
iron buildup in adult men and postmenopausal women.6
Upon closer inspection, many health-promoting practices inadvertently
control iron. For example, taking an aspirin a day to prevent
heart attacks and strokes causes blood loss via the digestive
tract on the order of about a tablespoon per day. This results
in iron loss.7 Raymond Hohl, M.D., an assistant professor
of internal medicine and pharmacology at the University of
Iowa in Iowa City, says even chronic use of a baby aspirin
may help to control iron and in some cases can induce iron-deficiency
anemia.8 Aspirin also appears to increase the production of
ferritin, an iron-binding protein that prevents iron from
inducing oxidation.9 By exercising, a person loses about 1
mg of iron through sweat.10 Fasting and vegetarian diets,
both of which promote longevity in animals and humans, limit
iron consumption because red meat contains the highly absorbable
heme iron. Whether or not related to iron consumption, restricting
red meat consumption has been shown in various studies to
reduce the risk of colon cancer.11
Normal Iron Regulation
In healthy individuals there is little if any unbound iron
circulating in the blood. In all disease states, however,
unbound iron (also called free iron) is released at sites
of inflammation and can spark uncontrolled oxidation.12 Fortunately,
there are numerous automatic mechanisms in the body that help
to control iron, many by chelation--compounds that bind to
a toxic substance (such as iron) and render it nontoxic or
nonactive. Albumin, a simple protein found in blood, acts
as a chelator by loosely binding to iron.13 Ferritin, produced
in the liver, is another iron-binding protein.14 Transferrin
is a protein that chelates iron and totes it back to the liver,
where it is metabolized and excreted.15 The liver produces
lactoferrin, another iron chelator, when challenged by infectious
agents.16 This is important because pathogenic organisms such
as viruses, bacteria and fungi require iron for growth. Furthermore,
as iron stores increase, the gastric absorption of iron decreases.
So the body employs numerous mechanisms to control iron that
are activated when threatened by disease. However, these defensive
mechanisms can be overwhelmed.
Blood tests for iron levels (i.e., hemoglobin and ferritin
levels are checked for transferrin saturation percentages)
are often useful, but the results of these tests are confounded
in states of prolonged inflammation or disease.17 A skilled
hematologist is often the best professional from whom to obtain
personal information concerning blood iron levels.
Differentiating between anemia and iron overload can be difficult
because both conditions cause fatigue. One study at the Department
of Medicine, University of Western Ontario in Canada, found
that iron overload can produce a wide range of symptoms, such
as joint pain (particularly hip), unexplained gastric pain,
frequent infections, skin bronzing, elevated liver enzymes,
cessation of menstruation, hair loss and heart flutters (fibrillation).
Yet, of 410 iron-overload patients, 27 percent experienced
no symptoms whatsoever.18 Common symptoms of iron-deficiency
anemia are lowered resistance to infections, fainting, breath
holding, mental fatigue, sleepiness, cold hands and feet,
and cravings for ice, meat or tomatoes, all which are more
likely to occur among women.19
Dietary Iron Control
Various dietary practices can help control iron levels. In
a relatively short period of time, dietary changes can result
in anemia, iron overload or an ideal state of iron control.
Anemia can be induced in about 120 days, while symptoms of
iron overload can come on in just 60 days.
Humans absorb only a fraction of the iron they consume, but
there are many controlling factors.20 Iron absorption rates
from food vary widely, from less than 1 percent to nearly
100 percent.21 Cooks who use iron or stainless steel pots
increase the amount of iron they consume.22 Generally, iron
in plant foods is not as well absorbed as iron from meat:
Only 5 percent of iron in plant foods is available, vs. 30
to 50 percent of iron from meat.23 Olive oil and spices such
as anise, caraway, cumin, licorice and mint promote iron absorption,24
while antacids, eggs and soy reduce availability.25 Since
dairy products contain lactoferrin, milk also inhibits the
absorption of iron.26 Moderate alcohol consumption is unlikely
to pose a problem with iron absorption, but excessive amounts
of alcohol is associated with iron overload, particularly
in adult males.27
Vitamin C also increases iron absorption.28 However, there
is no evidence that vitamin C leads to iron overload. Thus
vitamin C should not be avoided by meat-eaters for this reason,
since studies show high-dose vitamin C supplements are associated
with a decreased risk for heart disease, cancer, cataracts
and other disorders.29 A vegetarian diet does not generally
cause iron-deficiency anemia because there is more vitamin
C in plant-food diets, which enhances absorption.30
A 1982 human study was conducted to assess the effect of
various drinks on iron absorption. A subject ate a standard
meal of a hamburger, string beans, mashed potatoes and water.
When green tea was drunk instead of water, iron absorption
was reduced by 62 percent. Coffee reduced iron absorption
by 35 percent, whereas orange juice (as a source of vitamin
C) increased absorption by 85 percent. Contrary to other studies,
milk and beer had no significant effect.31
Bioflavonoids (found in berries, coffee, green tea, pine
bark, quercetin and the rind of citrus fruits, particularly
blueberry, cranberry, elderberry and grape seed) and phytic
acid (a component of whole grains and seeds such as sesame)
bind to iron and other minerals in the gastric tract and help
to limit iron availability. If bioflavonoids and phytic acid
haven't bound to minerals in the digestive tract they will
get into the bloodstream, where they can bind to free iron,
acting as blood-cleansing iron chelators. Therefore, maximum
iron chelation in the blood circulation is achieved when these
iron binders are consumed apart from meals.
Phytic acid--also called inositol hexaphosphate, or IP6--is
comprised of six phosphorus molecules and one molecule of
inositol. It has been mistakenly described for decades as
an "anti-nutrient" because it impairs mineral absorption.
However, in the 1980s food biochemist Ernst Graf, Ph.D., began
to tout phytic acid for its beneficial antioxidant properties
achieved through mineral chelation.32
Phytic acid in foods or bran should be distinguished from
supplemental phytic acid, which is derived from rice bran
extract. In foods, phytic acid binds to iron and other minerals
in the digestive tract and may interfere with mineral absorption.
As a purified extract of rice bran, taken between meals so
it will not bind to minerals in the digestive tract, phytic
acid is readily absorbed into the bloodstream, where it acts
as a potent mineral chelator.33 Phytic acid binds to any free
iron or other minerals (even heavy metals such as mercury,
lead and cadmium) in the blood, which are then eliminated
through the kidneys. Phytic acid removes only excess or unbound
minerals, not mineral ions already attached to proteins.
Phytic acid is such a potent--but safe--iron and mineral
chelator that it may someday replace intravenous chelation
therapy such as the mineral-chelator EDTA or iron-binding
drugs such as desferrioxamine (Desferal). Because of its ability
to bind to iron and block iron-driven hydroxyl radical generation
(water-based) as well as suppress lipid peroxidation (fat-based),
phytic acid has been used successfully as an antioxidant food
preservative.34
Phytic acid supplements should not be taken during pregnancy
since the developing fetus requires minerals for proper development.
Because aspirin causes a small loss of blood and consequently
helps to control iron levels, the simultaneous use of phytic
acid with a daily aspirin tablet is not advised. A three-month
course of phytic acid should achieve adequate iron chelation,
and prolonged daily supplementation may lead to iron-deficiency
anemia. Anemic individuals who take phytic acid as a food
supplement are likely to feel weak shortly after consumption,
whereas iron-overloaded individuals are likely to feel increased
energy.
For those at risk for iron overload, it may be wise to avoid
iron in multivitamins and shun fortified foods that provide
more than 25 percent of the recommended daily intake for iron.
No doctor should prescribe iron tablets for patients who complain
of fatigue without blood tests and a thorough health history.
Iron-rich foods such as red meat and molasses may prevent
anemia and build strength during the growing years but in
adulthood may lead to iron overload among men and postmenopausal
women. Those individuals who learn how to achieve iron balance
will maintain the most desirable state of health throughout
life.
Bill Sardi is a health journalist and
consumer advocate in Diamond Bar, Calif.
He recently published The Iron Time Bomb (Bill Sardi, 1999).
References
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Bill Asenjo, PhD, CRC
Writer; Consultant
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