Should Iron Be In Your Multivitamin?

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Should Iron Be In Your Multivitamin?

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Dec 12, 2004 18:30 PST

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Should Iron Be In Your Multivitamin?

A Literature Review and Conclusions

 

http://www.willner.com/References/webref36.htm

By Donald P. Goldberg, R.Ph

Willner Chemists

 

Introduction

 

As is the case with so many things, iron has two sides, and we have to

decide whether its advantages outweigh its disadvantages.

 

When evaluating the question of iron supplementation, we have to

remember that iron deficiency is one of the most common nutritional

shortfalls in the United States today.1 We have to remember, as well,

that we can be deficient in iron, and may be unaware of it.

 

" The initial stage of iron deficiency usually has no symptoms. It occurs

 

when the body’s iron stores are depleted or exhausted, a condition

reflected by a drop in the blood’s iron levels and an increase in

transferrin-a protein that transports iron through the blood stream.

 

As the iron supply to the bone marrow dwindles, so does the marrow’s

ability to produce healthy red blood cells, which require iron.

 

If the iron balance worsens, full-blown iron-deficiency

anemia-characterized by

low hemoglobin levels-can gradually develop.

 

Since iron is an essential component of hemoglobin, a shortage of iron

can impair the transport of

oxygen from the lungs to the body’s cells; as a result, work performance

will be impaired.

 

" It can take months or even years for symptoms of iron deficiency-such

as weakness, shortness of breath, paleness, poor appetite, and increased

susceptibility to infection-to become evident. These usually disappear

when iron stores are rebuilt. "

 

On the other hand, many people with " iron-overload " , or hemochromatosis,

often have no symptoms

 

Iron: Why Is It Essential?

 

All cells in the body contain iron. It plays a vital role in many

biochemical reactions. Perhaps its most important role is related to its

 

incorporation in hemoglobin, the oxygen-carrying protein that gives

blood its red color, and in the myoglobin in muscle.

 

Myoglobin, like hemoglobin, is a transporter of oxygen-it supplies

oxygen to the muscle cells for use in the chemical reaction that results

in muscle contraction.

 

Low iron intake over a long period of time can gradually

lead to a depletion of iron stored in the body. This is of special

concern when there is loss of blood, as in menstruation. " Iron is

therefore the main determinant of how much oxygen reaches and is used by

all body tissues, including the brain, muscles, heart, and liver. "

 

" Iron is also necessary for collagen synthesis. Iron is found in the

brain as a cofactor in neurotransmitter synthesis for serotonin,

dopamine, and noradrenalin, which are known to regulate behavior. "

 

" Iron strengthens the immune system and increases resistance to colds,

infections, and disease. "

 

As the iron supply to the bone marrow dwindles, so does the marrow’s

ability to produce healthy red blood cells, which require iron.

 

If the iron deficiency continues, full-blown iron-deficiency anemia,

characterized by low hemoglobin levels, can develop.

 

" It can take months or even years for symptoms of iron deficiency-such

as weakness, shortness of breath, paleness, poor appetite, and increased

 

susceptibility to infection-to become evident. These usually disappear

when iron stores are rebuilt. "

 

Why is Iron Supplementation Necessary?

 

According to Murray, " Although the human body contains only about 0.004

percent iron, it is one of the most significant elements in nutrition

and consequently very necessary to life.

 

Iron deficiency is said to be the second most common nutritional problem

in the United States, following obesity. " 13

 

" Without an adequate iron supply, people are at risk for developing a

variety of symptoms, such as reduced work capacity; more rapid build-up

of lactic acid in exercising muscle; irritability and apathy; lower

resistance to infections; spoon-shaped, thin nails; and pale nail beds.

 

It is difficult to get sufficient iron from the diet because all food

sources are not all equal in value. For example, spinach is rich in

iron, but the mineral is bound by chelates and takes it out of the body

before it can be properly absorbed. Other chelates include tannins in

tea; phytates in whole grains, brans and soybeans; polyphenols in

coffee; and phosvitin in egg yolk . "

 

" Unusual food cravings are associated with an iron deficiency.

 

Cravings for ice, starch, clay, and other nonfood items have been

attributed to a deficiency. Children who are deficient have a tendency

to hperactivity,

decreased attention span, and lower IQ’s. This conditions can be helped

if iron amounts are restored. "

 

" Iron is the most important mineral for the prevention of anemia during

menstruation. Iron may also be beneficial in the treatment of leukemia

and colitis.

 

Plummer-Vinson syndrome is cured with iron. This disease

can lead to esophageal and stomach cancer. Candida and herpes simplex

are helped with sufficient levels of iron if deficient already.

 

Iron-requiring proteins generate oxygen radicals that kill bacteria like

the ones in mother’s first milk. Muscle weakness and exercise endurance

are improved with iron. Both cardiac and muscular performance are

included. "

 

Are conditions such as anemia, impaired immune function and fatigue the

only examples that optimal levels of iron intake is important?

 

Not at all.

It has been know for many years that there is a connection between low

iron levels and " restless legs syndrome. "

 

A recent study at Royal Liverpool University concluded that " Iron

deficiency, with or without anemia, is an important contributor to the

developement of Restless Legs Syndrome in elderly patients, and iron

supplements can produce a significant reduction in symptoms.

 

A recent report in Tufts University Health & Nutrition Letter lends

further support to this relationship.

 

" Up to five percent of the population has restless leg syndrome--an urge

to move the legs, often accompanied by a creeping, crawling, or tingling

sensation, which worsens when the body is inactive and thereby causes

significant sleep disruptions.... But studies have indicated--and

clinicians at various sleep disorders centers have found--that in

patients with low levels of iron, iron pills may be all it takes to

relieve symptoms and allow for a good night’s sleep. "

 

They go on to point out that the " iron deficit doesn’t have to be very

large...research has found that even people whose serum ferritin falls

between 20 and 50 and therefore technically have a normal level can

sometimes benefit from iron supplementation. " According to Dr.

Ehrenberg, of the New England Medical Center Sleep Disorders Unit,

" There’s even a small percentage of people with serum ferritin levels of

50 to 100 who respond " to iron supplementation with reduced restless leg

symptoms.

 

Why is Iron Supplementation Discouraged by Some?

 

It has become popular to warn about the dangers of iron.

 

There is the author who " was forced to give up her career after being

stricken with an unidentified disabling illness. After 12 years of going

from doctor to doctor, she was finally diagnosed with iron overload and

elevated

levels of aluminum, lead and copper...

 

Following her treatment and recovery, she began researching the

scientific literature on the subject of iron overload, a potentially

lethal, but underdiagnosed and

undertreated medical condition. Her book... " 4

 

Then, you have a occasional study that implicates iron with problems,

such as heart disease.

 

Probably the most often quoted study of this type is one published in

1992, usually referred to as the Finnish study.5

 

The fact that this study could not be duplicated in two subsequent

studies seems to have little effect on those who persist in looking to

blame iron for various health ills.

 

Dr. Steve Austin, for example, is quick to point out that " this is not

so with all such reports. For example, in the November 18, 1997 issue of

Circulation, a prospective study found ferritin to be the ‘strongest

risk predictor of overall progression of atherosclerosis. "

 

And Dr. Austin follows up with another article highlighting a study in

Greece that claims to show a relationship between dietary iron intake in

men and increased risk of heart disease.

 

A study of Finnish men published, 1992 made headlines when it offered

evidence that even " normal " levels of iron stored to the body may

increase the risk of a heart attack.

 

Is iron one more risk factor men should worry about?

 

Not at this point For one thing, a high level of iron may be a marker

for some other factor that’s the real culprit

Also, the men in the study already had relatively high iron levels

compared to Americans, as well as a high incidence of heart

attacks—among the highest in the world.

 

Another point: only a small amount of dietary iron is absorbed by the

body, and that amount is affected by many factors including other foods

you consume and your body’s needs.

 

Thus, an iron-rich diet doesn’t necessarily lead to iron overload,

 

At this point, there is not nearly enough evidence supporting the link

between iron and heart disease Until a stronger case is made, healthy

men should continue to eat foods that supply their daily requirement of

iron.

 

The problem with studies like this is that they deal in possibilities,

not facts. In other words, it is sometimes difficult to determine

whether we are looking a the cause, or the effect.

 

For example, a patient with high iron levels may have high levels

because he is a long-time heavy meat eater.

 

Is the fact that he is at high risk of heart disease a function of the

high level of stored iron, or is the iron merely a coincidental result

of the heavy meat diet, with other factors

related to animal fat intake the real culprit?

 

Another problem with iron is that iron storage diseases such as

hemochromatosis are more common than previously thought.

 

Iron and Lipid Peroxidation

 

All of the functions that iron performs in the body are based on its

ability to donate and accept electrons, i.e. participate in

oxidation-reduction reactions.

 

It is this characteristic that makes iron a highly reactive and

potentially toxic nutrient.

 

This can be said for many of the powerful antioxidants found throughout

biological systems.

 

It is now commonly accepted that the oxidation of low-density

lipoprotein (LDL) results in the modified LDL being taken up more

readily by macrophages, which results in the development of the fatty

streak, the initial lesion of atherosclerosis.

 

Iron, as well as copper,

has been shown to promote the modification of LDL in vitro and is

suspected of participating in these reactions in the body.

 

Is this really a problem?

 

Although many studies provide convincing evidence that iron does

participate in free radical reactions and the modification of LDL under

experimental conditions, it remains unknown what conditions must exist

in the body for iron to participate in these reactions.

 

Normally, the body takes great care in keeping iron in a nonreactive

state.

 

For

example, the potential for free iron to exist in serum is low, because

the iron transport protein, transferrin, is only approximately 30%

saturated with iron under normal conditions.

 

This allows for a large capacity to deal with changes in iron

concentration within the serum pool (Beard, 1993). Only as transferrin

saturation approaches 100% does

iron become available to participate in free radical generation under

normal conditions.

 

However, free iron has been observed in the plasma of

hemochromatosis patients whose transferrin saturation was much less than

100% (Aruoma et al., 1988).

 

This may be indicative an inability of transferrin to bind iron

sufficiently in hemochromatosis patients.

 

After delivery of iron to the cell, the transferrin-iron complex enters

the cell through receptor-mediated endocytosis.

 

Once in the cell, iron is

utilized by iron-dependent systems, and any surplus iron is stored

tightly chelated in a nonreactive state in ferritin and hemosiderin

(McCord, 1991).

 

Ferritin, because of its iron-binding properties, is a

strong cytoprotective antioxidant (Balla et al., 1992; Gutteridge and

Quinlan, 1993).

 

Moreover, pools of dormant ferritin mRNAs exist in the

cytoplasm which can be rapidly translated to yield a large number of

ferritin subunits in response to increases in cellular iron (Munro,

1993).

 

This prevents the accumulation of iron within the cytoplasm and

the peroxidation of cell lipids, DNA, and various proteins.

 

If the storage capacity of ferritin is exhausted, excess iron is then

stored in the form of hemosiderin, which is a more insoluble iron

deposit that is not readily available to the organism (Welch, 1992).

 

Therefore, the association of iron with transferrin, ferritin, and

hemosiderin prevents iron’s participation in undesirable reactions

thought to be involved in the development of atherosclerotic lesions.11

 

Nevertheless, extreme levels of iron in the body can result in

myocardial tissue damage as evidenced by the clinical manifestation of

heart disease in hemochromatosis and other iron-storage disease

patients.

 

Furthermore, the ability of iron chelators to reduce injury to

heart tissue immediately after a cardiac arrest demonstrates that iron

does contribute to heart damage age after a heart attack has occurred

 

(Babbs, 1985; Bernier et al., 1986; Williams et al., 1991).

 

However, it must be recognized that these are extreme conditions that do

not implicate normal iron status as a risk factor for atherogenesis in

healthy individuals.

 

Free radicals are generated in the body as part of normal cellular

processes. For instance, the body utilizes free radicals as a way to

kill invading bacteria.

" Fortunately, free radical scavenger systems, such as superoxide

dismutase and glutathione peroxidase, exist to

prevent or terminate the undesirable accumulation of free radicals

generated in these situations.

 

Consequently, nutritional status of nutrients known to have antioxidant

functions or integral roles in free

radical scavenger systems (i.e. copper, zinc, selenium, carotenoids, and

 

vitamins A, E, and C), is important to consider.

 

It may be a deficiency of these nutrients that creates an opportunistic

environment that promotes atherosclerotic sclerotic lesions and not just

the presence of

transitional metals such as iron (Ames et al., 1993; Manson, 1993... " 11

 

The Finnish Study

 

We have already alluded to the often quoted Finnish Study (Salonen,

et.al, 1992. They found that eastern Finnish men with serum ferritin

levels greater than 200 µg/L had a 2.2-fold risk-factor-adjusted risk of

 

acute myocardial infarction (AMI) compared with men with lower serum

ferritin levels. This was a prospective 3-year followup study of 1931

eastern Finnish men aged 42, 48, 54, and 60 years who had no previous

history of heart disease upon entry into the study.

 

Although these results indicate that serum ferritin in the uppernormal

range was a risk factor for AMI in the population studied, it has been

questioned whether the data can be readily extrapolated to other groups

(Beard, 1993).

 

The nutritional patterns of a similar group of eastern

Finnish men were reported by Ihanainen et al. (1989), who collected

nutritional data on 1157 eastern Finnish men aged 54 years.

 

Results of this analysis showed the consumption of vegetables in this

population to be low (110 g/day), whereas coffee (586 g/day) and fat

intake (40% of energy intake) were high.

 

Intake of saturated fat was four times greater than that of

polyunsaturated fat, and dairy product consumption

consisted of 70% butter. Meat intake comprised mainly sausage (39%),

beef (37%), and pork (21%), and the mean daily intake of cholesterol was

480 mg.

 

The average intake of nutrients known to protect against lipid

peroxidation, such as vitamin E, copper, and selenium, was below

recommended dietary allowances.

 

The authors of this study indicated their findings were consistent with

other studies that have evaluated the diet of the Finnish population

(Uusitalo, 1987; Seppanen, 1981).

 

The enormous range in serum ferritin levels (10-2270 µg/L) in these

subjects is a strong indicator that the recessive hemochromatosis gene

was present in this cohort and possibly driving the observed association

between stored iron and AMI (Beard, 1993).

 

Other explanations for such high serum ferritin levels include the

presence of undetected conditions

known to elevate ferritin levels, such as liver disease and cancer

(Finch et al., 1986).

 

It is these population attributes and the fact that eastern Finnish men

have the highest recorded incidence and

mortality from CHD (Keys, 1980) that makes extrapolation to other

populations difficult.

 

Moreover, although ferritin was found to be a significant risk factor

for AMI with a relative risk of 1.03 in this population, several other

factors were also found to be statistically

significant and have greater relative risks for AMI than serum ferritin.

 

 

For instance, serum copper, serum apolipoprotein B, and diabetes had

approximately 600, 400, and 250 percent greater relative hazards of AMI

than ferritin, respectively.

 

The weaker association of ferritin to AMI compared with these other

factors may be due to ferritin’s ability to sequester iron in a

nonreactive form (Balla et al., 1992; Gutteridge and Quinlan, 1993).11

 

Does Iron Accumulate With Age?

 

Much of the concern about iron in supplements arises from the belief

that in men, especially sedentary men, there is little means by which

stored iron can be lost, and therefore it continues to build up over the

years, eventually reaching " overload " levels.

 

This may not be the case:

 

The hypothesis that iron stores are related to the risk of

cardiovascular disease (CVD) arose in part from the observation that the

incidence of CVD increases with age in men and in postmenopausal women

(Kannel et al., 1976; Gordon et al., 1978).

 

Other studies reported that iron stores also accumulated with age in men

and in postmenopausal women

(Cook et al., 1976). Thus, Sullivan hypothesized that the two

observations were related (Sullivan, 1981).

 

However, NHANES II and NHANES III pilot study data appear to indicate

that iron may not accumulate with age.

 

Figure 1 represents data of mean serum ferritin values of non-hispanic

white (NHW) males and females at various ages

from NHANES II and NHANES III pilot data of all persons measured. As can

be observed from the graph, ferritin values do not increase appreciably

with age in men, but values do increase in women as they pass through

menopause.

 

Interestingly, Solonen et al. (1992) reported that serum

ferritin concentrations decreased after 48 years of age in the eastern

Finnish men they studied.

 

The recent proposal of a setpoint theory, whereby iron stores regulate

iron absorption to maintain an individual’s preset iron stores,

challenges the idea that iron stores accumulate with age.

 

Garry et al.

(1992) proposed the setpoint theory after assessing iron stores in 27

postmenopausal healthy women who donated 5 units of blood over 1 year

compared with 59 controls. Iron stores in the control group did not

change over 2 years, despite large differences in baseline iron stores

and similar dietary iron intakes.

 

The authors speculated that a setpoint exists for individual iron stores

which is under genetic control. If this is so, it would be difficult to

increase iron stores through diet

or supplementation when iron stores are at or near an individual’s

predetermined " setpoint " .

 

Gavin et al. (1994) further investigated the setpoint theory in 21

individuals selected from the same study population as that used by

Garry et al. (1992). Iron absorption changed according to changes in

baseline iron stores, and 70% of the variation

in iron absorption was explained by the changes in iron stores from

baseline, indicating an adaptation to the level of depletion of iron

stores below the setpoint.

 

If iron stores are regulated as described by the setpoint theory, iron

stores would not be expected to increase with age.

 

Is Low Iron Protective Against Heart Disease?

 

If high iron levels are related to increased risk of heart disease, as

some claim, it would be logical to assume that low levels would infer a

protective effect. But this does not seem to be the case.

 

Within the iron/heart disease paradigm, it would be predicted that other

 

indicators of iron deficiency, such as a low transferrin saturation

(serum iron divided by total iron binding capacity x 100), would

indicate protection against heart disease, because a low transferrin

saturation would possess potent antioxidant activity.

 

As indicated by Beard (1993), determination of transferrin saturation

could provide a better understanding of the association of iron and

heart disease.

 

Magnusson et al. (1994) studied 2036 men and women between the ages of

25 and 74 years who were participating in a large epidemiological study.

It was found that increased total iron binding capacity (TIBC) was

protective against MI, whereas serum ferritin had no significant

association.

 

It was also observed that transferrin saturation had less

predictive power for MI than did TIBC. Another study was recently

completed on 46,932 subjects whose serum iron and TIBC were measured and

 

who were followed for a 14-year period (Baer et al., 1994). During the

followup period, 969 men and 871 women had an AMI-related hospital stay.

 

 

Results did not show iron deficiency, as indicated by low transferrin

saturation, to be protective against heart disease. Liao et al. (1994)

examined data from the 4237 respondents of NHANES I aged 40-74 years

(1827 men and 2410 women). Hemoglobin, serum iron, and the total

iron-binding capacity of transferrin (TIBC) were determined. During the

13-year followup, 489 persons had an AMI, and 1151 developed CHD.

Hemoglobin, hematocrit, and TIBC were not associated with the incidence

of MI or CHD.

 

Transferrin saturations in both men and women who developed CHD were

lower than in those who did not, and each 10% increase in transferrin

saturation was associated with a 9% decrease in

risk of CHD among men and a 12% decrease among women.

 

The authors caution that these results are only suggestive, because the

influence of diurnal variation and other factors such as inflammation

and malignancy were not monitored or controlled. Sempos et al. (1994)

also assessed the

association between the risk of MI and serum transferrin saturation 4518

men and women who were part of NHANES I. The risk of CHD was not

related to transferrin saturation levels, and results indicated there

may even be an inverse relationship.

 

Other Research On Iron and Cardiovascular Disease

 

As briefly mentioned earlier in this report, there is a considerable

body of research that does not support the proposed connection between

iron and heart disease.

 

The following summary was presented in the article by Proulx and Weaver.

 

Since the publication of the Finnish study by Salonen et al. (1992),

many other studies that have investigated the association of iron and

heart disease have been completed.

 

Researchers from the Karolinska Institute in Stockholm, Sweden,

conducted a case-control study to investigate the effect of iron on the

risk of AMI at a young age (Regnstrom et al., 1994). Ninety-four men who

experienced an MI before the age of 45 years were compared with 100

age-matched population controls.

 

There was no association between the measure of iron status

and severity of coronary atherosclerosis, suggesting that iron stores

were not a risk factor for premature coronary atherosclerosis.

 

In another investigation, 252 patients between the ages of 29 and 84 who

 

were admitted for cardiac catheterization to Duke University Medical

Center also had their blood analyzed for serum ferritin, total iron,

TIBC, and transferrin along with lipoprotein profiles (Lin et al.,

1994).

 

When coronary artery disease (CAD) risk factors (age, sex, body

mass index, lipid-lowering drugs, smoking, and special diet) were

controlled for, no relationship between indicators of iron status and

extent of CAD was found.

 

A prospective study of plasma ferritin and risk of MI in 238 men with

MI and 238 controls matched for age and smoking

found that, after adjustment for other coronary risk factors, men with

serum ferritin levels greater than 200 µg/L had a relative risk of 1.1

(Stampfer et al., 1993).

 

This suggests little or no increased risk associated with normal

ferritin levels. Aronow (1993) evaluated the association between serum

ferritin levels and CAD in 171 men and 406

women. The mean age of men (n = 74) and women (n = 172) with CAD was 82

years; that of men and women without CAD was 81 years.

 

The mean serum ferritin concentration was not significantly different

between men and

women with and without CAD, indicating ferritin was not a risk factor

for CAD in these elderly men and women. Miller and Hutchins (1993)

selected 130 adult patients from 48,000 autopsy records performed from

1889 to 1993 at Johns Hopkins University. These patients were carefully

matched for age, sex, and time of death. Sixty-five of these had iron

overload and 65 did not.

 

The researchers concluded that people with iron overload did not appear

to have significant amounts of CAD. Only 3 of

the 65 patients with iron overload had one coronary artery with 90% or

more blockage.

 

Salonen et al. (1992) also reported that the intake of dietary iron was

strongly associated with the risk of AMI in eastern Finnish men.

However, Rimm et al. (1993) measured dietary iron intake through a food

frequency questionnaire during a 4-year followup of 45,720 men aged

40-75 years with no previous history of heart disease.

 

Eight-hundred eighty cases of coronary disease were documented, and,

after adjusting

for other risk factors, men with the highest intake of iron had an

insignificant relative risk of heart disease compared with men with the

lowest intake of iron.

 

The relative risk of CHD for each milligram

increase in dietary iron was 1.0, indicating no increased risk.

 

Ascherio and Willet (Harvard 1994) studied iron intake and its

association with coronary

disease in 44,933 men aged 40-75 years and found that

 

higher intakes of heme iron were associated with greater risks for MI

but not dietary iron in general.

 

Is Lower Heart Disease Among Premenopausal Women Due To Lower Iron

Levels?

 

Based on the iron/heart disease theory, premenopausal women are thought

to have increased protection against heart disease due to iron loss as a

result of menstruation.

 

If iron loss via menstrual blood flow was responsible, those women who

take oral contraceptives, which decreases

menstrual blood flow, would not exhibit this protective effect.

 

In fact, significant differences in iron stores have been found between

users and nonusers of oral contraceptives (Frassinelli-Gunderson et al.,

1985).

But this does not seem to be related to iron levels in the body.

 

Moreover, earlier studies found that current and discontinued use of

oral contraceptives was associated with an increased risk of heart

disease (Slone et al., 1981).

 

Dr. Sullivan hypothesized that the increased risk for CHD among oral

contraceptive users was due to the accumulation of iron (Sullivan,

1981).

 

A recent study on the effects of low-dose oral contraception on

menstrual blood loss and iron status found that menstrual blood loss was

reduced by approximately 44% in

women taking low-dose oral contraceptives (Larsson, 1992).

 

However, serum ferritin concentrations in these subjects remained

unchanged over the 6-month period of the study. Stampfer et al. (1988)

studied 119,000

women who were 30 to 55 years of age and found that the use of oral

contraceptive agents in the past did not raise a woman’s risk of heart

disease.

 

 

On the other hand, current users of oral contraceptives did have an

increased risk of CHD of 2.5, but this excess risk was observed

predominately in smokers.

 

Porter et al. (1985) studied more than 65,000 women, 15 to 44

years of age, who were healthy nonsmokers and found that no MIs occurred

in users of oral contraceptives. The 11 deaths due to CVD in the 6-year

period occurred in the women who were not using oral contraceptives

(Porter et al., 1987).

 

In another study, an increased incidence of heart disease was found

only

among older users who had other known risk factors for heart disease

(Mann et al., 1976). Mant et al. (1987) analyzed results from a large

cohort study in Britain and found the risk ratio for MI in current users

 

of oral contraceptives was not increased, and no MIs were found in women

who used formulations with less than 50 µg of estrogen.

 

Therefore, the increased risk of heart disease that has been observed in

women who use oral contraceptives, past and present, appears to be

strongly associated

with the dose of estrogen and smoking habits rather than iron stores.

 

 

Summary

 

There is no question that in certain circumstances the accumulation of

excess iron is possible. In its most severe form, hemochromatosis, large

amount of iron can be deposited in the liver, spleen and other tissues,

causing pronounced impairment in function and tissue damage. This

condition was thought to be rare, and usually associated with a genetic

disorder that results in abnormal absorption or iron.

 

On the other hand, adequate levels of iron is essential to optimal

health.

Even in the absence of overt anemia, iron deficiency can produce such

symptoms as fatigue, behavioral problems

(decreased alertness and attention span), muscle weakness and increased

susceptibility to infections.17

 

Even if iron-overload is more common than once was thought, the evidence

does not support a blanket recommendation that iron be completely

eliminated from the diet, or from supplementation, for certain

population groups.

 

The average American diet is too poor, and iron

deficiency is too prevelant, to make such a generalization.

 

While there may be a preponderance of anti-iron commentary in certain

areas, it is important to maintain a proper perspective, especially when

 

looking at epidemiological studies.

 

For example, it is known that

Candida infections of the skin and mucous membranes are more common in

patients who are iron deficient.

 

This is true for herpes simplex infections as well. Certainly, the

majority of those who are outspoken

critics of iron supplements are at the same time aware of what could

almost be called a " candida epidemic. "

Can we not then conclude that

this epidemic of candida albicans is related to low iron levels?

 

The same could be said, perhaps, of what we are calling " chronic fatigue

syndrome. "

 

Muscle weakness and decreased exercise tolerance are

frequently associated with iron-deficiency anemia.

 

But these symptoms can occur even when there is iron deficiency but not

anemia and can be resolved when the iron deficiency is corrected.

 

And, as pointed out by Dr. Murray, when commenting on the oft-quoted

Finnish Study, " Another way of expressing the results of the study would

be to simply state that Finnish men eating more meat have an increased

risk for heart attacks, elevated LDL-cholesterol levels, and elevated

iron stores.

 

Therefore, the study simply provided additional evidence

that high meat intake increases the risk of heart attack. This is

nothing new; it is just a different way in which high meat intake can

lead to premature death. "

 

The same can be said for a more recent report concerning iron

supplements and colorectal cancer. In the recent edition of Nutrition

Science News, (June 1999, Vol.4, No.6) the headline in their " Natural

News " section reads " Extra iron Spawns Free Radicals in Gut. "

 

The article starts off with the following sentence: " People who take

dietary iron supplements may run an increased risk of colorectal cancer,

suggests recent research that draws a direct correlation between iron

intake and free radical generation. "

 

This is misleading. As they go on to say, " …studies since have found

that people with iron-heavy diets, such as meat eaters, have more colon

cancer. "

 

Again, as Dr. Murray pointed out, this may or may not be

directly related to iron.

 

Other aspects of a heavy meat eater's diet may be responsible for this

association with higher rates of colon cancer.

 

In this particular study,19 what they actually did was look at the feces

of 18 healthy people who supplemented for two weeks with an additional

19 mg of iron. They collected the feces, and measured iron levels and

free radical production.

 

Since we know that most iron is not absorbed, it would be expected that

the level in the feces would increase, and it

did, along with free radical production.

 

This free radical increase was measured outside the body, however. We do

not know what significance, if any, this might have inside the bowel.

 

Nor do we know with any certainty that this iron induced free radical

generation has any significance toward disease.

 

In fact, interestingly enough, in the same issue of Nutrition Science

News, in an article on probiotics, the author explains that one of the

most important functions of probiotic organisms (acidophilus, bifidus,

etc) to limit the growth

of pathogenic organisms.

 

How do these friendly bacteria do that?

 

They " …secrete substances-lactic acid and other organic acids, hydrogen

peroxide, and potent antibiotic agents known as bacteriocins-that

inhibit the growth of harmful organisms. "

 

Please note that hydrogen peroxide is a powerful source of free radical

oxygen.

 

So it is important to put reports such as this in proper perspective.

 

Remember, what we have is a connection between people with a certain

dietary pattern, high meat eaters, and increased risk of certain

diseases.

 

It so happens that high meat intake normally results in high

iron levels. This does not necessarily mean that the iron is responsible

for the disease.

 

A study such as the one reported above, looking at iron intake, and

resultant levels in the feces, can only lead to two conclusions:

 

First, as we would expect, increased iron intake results in increased

levels of iron in the stool, and second, the increase iron in the stool,

at least in vitro, can lead to increased levels of free radicals in the

stool.

 

If we choose to believe that it is the iron, rather than other meat- or

life-style related factors that might be responsible for the disease

assocated with this group, then this study provides clues as to what the

mechanism might be. But that is all.

 

Another interesting finding by the authors of the study, by the way, was

 

that " Higher carbohydrate diets were associated with reduced free

radical generation. "

 

The following conclusion by Proulx, et.al. sums it up quite nicely:

 

" Although the iron and heart disease hypothesis offers an intriguing

explanation for many of the factors associated with heart disease,

subsequent research has not been supportive of the paradigm.

 

Confounding variables inherent in the study of eastern Finnish men

(i.e., the

presence of serum ferritin levels of 2200 µg/L, the known high level of

CAD, high concentration of LDL, and the potentially atherogenic diet in

this population) make definitive conclusions and extrapolations to other

population groups difficult.

 

However, other factors analyzed in this investigation that were found to

have more substantial relative risks for AMI than ferritin may be worthy

of further investigation.

 

Manttari et al. (1993) found that there was a linear trend in CHD risk

with increasing " ceruloplasmin " , the copper 'transport protein', in

dyslipidemic men.

 

In the Finnish study, " serum copper " had the highest relative risk of

all factors analyzed.

 

Numerous studies investigating the relationship between iron and heart

disease largely have been unable to support the

findings of the Finnish study and the iron/heart disease paradigm. On

the other hand, research supporting estrogen as the main factor

explaining the difference in rates of heart disease between men and

premenopausal women is convincing.

 

Nevertheless, when the negative consequences of iron deficiency are

considered along with the prevalence of iron-overload disease, prudent

but timely action on this issue is imperative.

 

Universal screening for iron storage diseases as recommended

by Herbert (1992) seems to be an efficacious and reasonable approach to

the public health problem of iron overload, because measurements of iron

 

status are relatively inexpensive and effective treatment is available.

 

Those found to have levels of iron that would put them at risk for

toxicity should be advised to reduce their iron levels and avoid iron

supplements. Otherwise, until sound scientific evidence indicates

differently, the rest of the general public should be encouraged to

consume as near the RDA for iron for their age and gender as

possible. "

 

A similar conclusion was arrived at by Corti, et.al. in their 1997

paper: " Free iron, as well as other transition metals, can catalyze free

radical formation.

 

For this reason iron is tightly bound to transport and storage proteins

to prevent their involvement in " free radical "

formation.

 

It has been hypothesized that increased iron intake or iron

stores may promote atherogenesis by increasing free radical formation

and oxidative stress.

 

While a coherent, plausible hypothesis as to how transition metals,

such as iron, might accelerate the progression of

atherosclerosis has been generated from basic research, iron status,

measured as dietary iron intake, serum iron, serum ferritin, and

transferrin saturatgion, has bee inconsistently associated with

cardiovascular disease in human epidemiologic research.

 

In addition, limited data suggest that iron overload states do not

appear to bestrongly associated with increased risk of atherosclerotic

disease...At

present the currently available data do not support radical changes in

dietary recommendations or screening to detect high normal levles nor do

they support the need for large-scale randomized trials of dietary

restriction or phlebotomy as a means of lowering iron stores. "

 

The rational approach

 

Holford, in his book The Optimum Nutrition Bible, discusses the Finnish

Study, and the correlation between blood ferritin levels and

cardiovascular risk.

He reports Sullivan’s theory that " this might explain why menstruating

women, who lose iron each month, have a lesser risk of cardiovascular

disease than men until after the menopause. "

 

But he concludes that " This theory is yet to be proven, but suggests

that meat-eating men should not go overboarfd on iron supplements.

 

In practice, this means limiting the dose to 10 mg a day.

 

" The toxicity of iron is low, and harmful effects of daily intakes of up

to 75 milligrams per day are unlikely in healthy individuals.

 

The body has a highly effective mechanism that prevents an overload of

iron from entering it and causing toxicity.

 

The amount of iron the body absorbs is carefully regulated by the

intestines, according to the body’s needs.

 

The greater the need, the higher the rate of absorption.

 

Growing children, pregnant women, and anemic individuals have higher

rates of absorption. When a deficiency occurs, the rate of absorption

increases to two to three times higher than normal.

 

(Unfortunately, this

response does not appear to be sufficient to prevent anemia in

iron-deficient subjects who are only mildly anemic and whose iron intake

is marginal.)

 

There have been conflicting scientific reports concerning iron and the

risk of coronary heart disease.

Some studies have shown that high iron levels in the blood appear to

increase the risk of heart disease, while

other studies have failed to confirm these findings.

Some studies have demonstrated that high levels of serum ferritin (a

complex in which iron

is stored in the tissues) or of total iron binding capacity (TIBC)

appear to increase the risk of heart disease, while other studies have

failed to confirm these findings, as well. What does all this mean?

 

We know that antioxidants are our natural defense against free radical

oxidative stress, and that iron is a very powerful pro-oxidant-an

initiator of oxidative stress.

 

The discrepancies in the study findings

may be the result of the balance of antioxidants and iron.

 

Even though iron is essential to the functioning of our bodies, too much

 

iron combined with poor antioxidant defense, due to poor intake of

antioxidants would put anyone at high risk for increased oxidative

stress, which is believed to be a culprit in heart disease.

 

Since we can easily measure iron, TIBC, and ferritin levels in our

blood, these levels should routinely be screened during physical exams.

If high levels are present, a reduction of iron intake should be

discussed with your physician.

 

In some cases, a dangerous condition known as hemochromatosis can cause

the excessive absorption of iron.

 

This results in a build-up of excess

iron in the tissues of many organs, possibly leading to damage to the

liver, heart, pancreas, and other organs. 1n genetic hemochromatosis,

there is inappropriately high absorption of dietary iron from birth.

 

Acquired hemochromatosis may occur as a result of transfusions, medical

conditions, or excessive long-term iron intake, This condition, too, can

 

easily be detected through blood tests. If the tests confirm the

condition, steps should be taken to avoid iron in food and supplements,

and to avoid foods cooked in cast iron cookware or stored in metal cans.

 

12

 

In response to the claim that iron promotes oxidation, contributing to

heart disease in men and rheumatoid arthritis, Dr. Saul Hendler offers

the following observation:

 

" That iron can generate free radicals is well

known. Unbound iron in the ferrous (or ‘plus two’) state is a potent

generator of hydroxy radicals, which can be very destructive to cells.

However, unbound iron occurs only under certain conditions.

 

Patients with hemochromatosis, a genetic disorder of excessive iron

accumulation, can have a significant quantity of unbound iron in their

cells, and this may give rise to extensive damage to liver, heart,

pancrease and skin.

 

These genetic disorders, however, are rare. And

there is no convincing evidence at present that iron is active in either

 

rheumatoid arthritis or atherosclerotic disease.

 

Most iron we come in

contact with is tightly bound to protein and does not generate dangerous

 

free radicals....Prolonged administration or iron supplements very

rarely causes iron overload...Iron supplements are widely used in the

United States, and reports of toxicity from iron overload are very

rare.17

 

And finally, the commentary on this question of iron levels and risk of

heart attack presented by Dr. Michael Murray in his book, " Encyclopedia

of Nutritional Supplements " , further helps to put the concern over

excess

iron into proper perspective:

 

" Recent news accounts highlight the possible relationship of elevated

iron levels and the risk for heart attacks. The articles in the popular

press are based on several scientific studies. However, the news

accounts do not provide all the information. For example, let’s look at

the study published in the medical journal Circulation.

 

In this study of Finnish men, researchers demonstrated that high

stored-iron levels

produced by a diet of excess meat is associated with excess risk of

heart attack, Although iron was singled out, the study also demonstrated

 

an increased risk for a heart attack when LDL-cholesterol levels were

elevated.

 

In other words, the strongest link between increased stored

iron levels and risk for a heart attack was found in men with

LDL-cholesterol levels greater than 193 milligrams per deciliter.

 

Furthermore, the strongest dietary link to an increased risk for a heart

 

attack in the study was meat intake. Meat intake was also linked to

increased LDL-cholesterol levels and increased dietary intake of

saturated fats.

 

Another way of expressing the results of the study would be to simply

state that Finnish men eating more meat have an increased risk for heart

attacks, elevated LDL-cholesterol levels, and elevated iron stores.

 

Therefore, the study simply provided additional evidence that high meat

intake increases the risk of heart attack. This is nothing new; it is

just a different way in which high meat intake can lead to premature

death.

 

Elevated levels of iron may lead to an increased risk of heart disease

by spinning off free radicals in the blood and either damaging

cholesterol or the artery walls directly.

 

Antioxidants like vitamin C and vitamin E protect against iron-induced

oxidative damage. "

 

Conclusion

 

For people who are not in the high risk group for iron deficiency (i.e.

none of the following: menstruating women, dieters, pregnant women,

endurance athletes, strict vegetarians, infants and children), it is

prudent to moderate or reduce iron supplement intake.

 

This would include men, especially heavy meat eaters.

 

Some experts indeed claim that " adult men who eat well-balanced diets of

2,000 calories or more do not need iron supplements.. "

 

This may be true, but the same can be said for all vitamins and

minerals, depending on your viewpoint. The problem, of course, is that

so few of us can claim to eat a well-balanced diet.

 

More realistic, in my opinion, is to reduce the amount of iron to a more

prudent level.

 

A level of less than 10 mg in a balanced multivitamin would be

appropriate.

 

It is important to utilize a multivitamin with a full spectrum of

antioxidants, to ensure, in addition to all the many

benefits antioxidants provide, that the iron does not function as a

pro-oxidant.

 

An additional antioxidant blend is usually desirable in any

case.

 

Those who feel that they might for any reason be in danger of too much

stored iron should have the appropriate blood tests run to determine

whether or not they have a valid reason for concern. The proper test for

this purpose would be a serum ferritin test, which measures how much

iron is stored in the body.

 

If there is insufficient reason to request a serum ferritin test, then I

suggest that there is insufficient reason to totally eliminate iron from

the daily supplement program.

 

The importance of adequate iron levels should dictate the inclusion of a

moderate level in the daily supplement program.

 

The realization that genetic iron overload disease is a more common

disorder than was one thought is not to be interpreted as justification

for depriving otherwise healthy adults of the benefits of iron

supplementation. Instead, it should be considered basis for increased

emphasis on blood test screening so that those individuals can be

properly identified.

 

There is no basis for totally restricting iron supplementation in the

absence of such clinical testing. As explained above, the value of iron

is too great to risk a deficiency.

 

While elderly men can be thought to be more likely to have adequate iron

stores, it should be remembered that elderly men are at the same time

more likely to have difficulty absorbing iron due to reduced levels of

" ydrochloric acid " in the stomach.

 

It should also be kept in mind that the actual amount of iron absorbed

from a supplement is small.

 

This is especially true when the supplement contains a large amount of

*calcium "

 

Just as calcium " interferes " with the absorption of lead, it interferes

with the absorption of iron.

 

The general rule of thumb, in fact, is that only about 10% of iron is

absorbed.

 

The actual estimated requirement for iron for adult men is

0.65 to 1.3 mg. This leads to a Recommended Daily Allowance of 10 mg

(National Research Council). The Food and Drug Administration, in

adopting the " US RDA " or " Percent Daily Value " for label purposes,

increased the level to 18 mg.

 

A level of 10 mg, therefore, is more in keeping with the level

recommended for men over the age of 19, and women over the age of 51.

 

For those in the other category, where there is little question but that

there is need additional iron supplementation, an additional supplement

and/or increased dietary heme iron intake is necessary. This would

include, of course, adolescents, premenopausal women, pregnant and

lactating women, those with anemia, dieters, " and the elderly with poor

dietary habits over long periods of time. "

 

Special Note: Willvite

 

In the product Willvite, a total multivitamin-multimineral supplement

formulated by Willner Chemists, the amount of iron present is 9 mg, per

four tablets, which represents 50% of the " Percent Daily Value " as

mandated by the FDA.

 

As explained above, for most people, we feel this represents an

appropriate compromise. In addition, the type of iron used

is a form bound to fumaric acid, the chelated ferrous fumarate.

 

This form, especially in the presence of a balanced array of

antioxidants, is considered safe and effective.

 

(For iron deficiency, for example, Dr. Michael Murray recommends " iron

bound to either *succinate* or *fumarate* " ).

 

References

 

1. Univ. of California at Berkeley Wellness Letter. The New Wellness

Encyclopedia. Houghton Mifflen Co. 1995.

 

2. Holford, Patrick. The Optimum Nutrition Bible. The Crossing Press,

1999.

 

3. Atkins, M.D., Robert. Dr. Atkins’ Vita-Nutrient Solution. Simon &

Schuster, 1998.

 

4. Lavie, Rebecca. Iron and Copper Overload. Consumer Health Newsletter.

 

21.6, 1198.

 

5. Salonen JU, Nyyssonen K, Korpela H, et al. High stored iron levels

associated with excess risk of myocardial infarction in western Finnish

men. Circulation 1992; 86:803-11.

 

6. Sempos CT, Looker AC, Gillum RF, Makuc DM. Body iron stores and the

risk of coronary heart disease. N Engl J Med 1994; 330:1119-24.

 

7. Baer DM, Tekawa IS, Hurley LB. Iron stores are not associated with

acute myocardial infarction. Circulation 1994; 89:2915-8.

 

8. Kechl S, Willeit J, Egger G, et al. Body iron stores and the risk of

carotid atherosclerosis. Circulation 1997; 96:3300-307.

 

9. Austin, Steve. " Is Iron Getting a Bad Rap? " Yes - And Well It Should!

Quarterly Review of Natural Medicine 03-31-98 p. 44

 

10. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary

heart disease risk: a study from Greece. Am J Epidemiol 1998; 147:161-6

 

11. Proulx, William R.; Weaver, Connie M. Ironing Out Heart Disease:

Deplete or Not Deplete? Nutrition Today 02-28-95 V.30; N.1 p. 16-23

 

12. Lieberman, PhD, Shari and Bruning, Nancy. The Real Vitamin & Mineral

 

Book, 2nd Ed., Avery Publishing Group, 1997.

 

13. Murray, Frank. The Big Family Guide to All the Minerals. Keats

Publishing. 1995.

 

14. Kirschmann, Gayla and John. Nutrition Almanac, 4th Ed. McGraw Hill

1996

 

15. Somer, Elizabeth. The Essential Guide to Vitamins and Minerals.

Health Media of America. Harper Perennial. 1992.

 

16. Courtenay, Gary and Smith, Catherine Joy. 100 Years Young. Apple

Publishing. 1997

 

17. Hendler, Sheldon Saul. The Doctor’s Vitamin and Mineral

Encyclopedia. Fireside, Simon & Schuster. 1991.

 

18. Murray, Michael. Encyclopedia of Nutritional Supplements. Prima

Publishing. 1996.

 

19. Lund, EK, et al. Am J Clin Nutr, 1999 Feb, 69:2, 250-5

 

20. Corti, MC. et al. Ann Epidemiol, 1997 Jan, 7:1, 62-8

 

21. O’Keefe, ST, et al. Age Ageing 23:200-203, 1994

 

22. Tufts Univ Health & Nutrition Letter. June 1999, 17:4

 

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of coronary heart disease. N Engl J Med 1994;330:1119-24.

_________________

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