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FOR IMMEDIATE RELEASE

Orthomolecular Medicine News Service, July 31 2023

The Toxic Nutrient Triad

A little: good. Just a little more: bad

Commentary by Thomas E. Levy, MD, JD

OMNS (July 31, 2023) Most clinicians are familiar with the concept that when a little is good, more
is often better, but a lot is still reliably toxic. This results in the mindset of there being little chance
of doing harm with supplementing a "little," especially when the supplements involved are well-
known and relatively popular supplements, widely regarded as being beneficial without question.
In the case of calcium, iron, and copper the downside of minimal supplementation could not be
more clear-cut. All three of these agents are essential for health, especially inside the cells.
Nevertheless, once a relatively low daily intake of these nutrients is exceeded only minimally,
toxicity rapidly ensues, with the highest intakes resulting in the greatest toxicity. This is in great
contrast with some other nutrients, such as vitamin C, niacin or niacinamide, or vitamin K2, where
toxicity is difficult to reach at any degree of intake or supplementation. Many other nutrient
supplements, especially minerals, can readily be ingested to the point of toxicity, but the amounts
needed are still much more difficult to reach compared to the minimally toxic intakes of calcium,
iron, and copper.

Cellular Calcium Excess Underlies Disease

The marketing efforts of the dairy industry over the years have been wildly successful in
convincing the public as well as most doctors that high calcium intake by diet (especially dairy),
and by extension, supplementation as well, is of clear benefit to general health and for healthy
bones as well. Unfortunately, the exact opposite is true, and excess calcium intake is the primary
fuel sustaining and even provoking heart disease, cancer, and all chronic degenerative diseases.

Elevated intracellular calcium levels are present in all cells affected by disease
processes, and very high levels are present in all malignant cells.

Furthermore, when therapeutic measures are taken to reduce these calcium levels, healthier cells
always result. [1]

Several straightforward studies revealed the tremendous toxicity of too much calcium. In a study
on 61,433 Swedish women followed for a median of 19 years, those who ingested the most total
calcium from both diet and supplementation had an all-cause mortality 250% greater than those
with the lowest intakes of calcium. Similarly, the same group with the greatest calcium intake had
a more than 200% increase in mortality from coronary artery disease. [2] A meta-analysis of 15
trials also clearly demonstrated an increased risk of myocardial infarction in patients who took
calcium supplements. [3]

The Coronary Artery Calcium (CAC) score has been used for over 30 years now to monitor the
likelihood of a patient dying of coronary heart disease (myocardial infarction). A higher score
indicates an increased chance of cardiac mortality. The CAC score is generated by a CT
(computed tomography) scan over the heart. Greater amounts of calcium deposition in the
coronary arteries consistently result in higher CAC scores. [4] Therapeutic measures that can
increase or decrease this calcium accumulation correlate directly with an increased or decreased
chance of cardiac mortality.

Recent research now indicates the CAC score is clearly predictive of all-cause mortality and not
just death from coronary artery disease. [5] This indicates that the CAC score also serves as a
reliable marker test for indicating the degree of calcium excess throughout the body and not just
in the coronary arteries. Having a high amount of calcium deposition in the coronary arteries
indicates calcium excess everywhere, even if it is only inside the cells and not as readily detected
as calcium deposits. While some excess intracellular calcium can still be present when the CAC
score is zero (normal), any positive score assures the presence of such excesses, with higher
scores indicating greater excesses and greater degrees of pathology in the body.

Menopause, with its loss of estrogen production in the affected women, contributes directly to
increased intracellular calcium levels.[6] Normal estrogen levels are very effective in minimizing
cytoplasmic calcium levels as estrogen serves as a calcium channel blocker, limiting calcium
uptake into the cells. Consistent with this, it has now been shown that menopause does promote
increased CAC scores. [7] Testosterone, the male sex hormone counterpart to estrogen, also
serves as a calcium channel blocker throughout the body. [8] This important relationship of
increased intracellular calcium levels resulting from decreased sex hormone presence only further
underscores the importance of giving some sex hormone support to all older patients, even when
the hormone levels are still technically above the lowest levels in the laboratory reference range.

To be clear, the very well-defined relationship between calcium content inside the cells of the body
and disease-causing increased intracellular oxidative stress really means only one thing: Never
supplement calcium.

Iron and Copper: The Toxic Transition Metal Twins

Why call these two metal twins? Basically, it is because these metals are both prominent
promoters of the Fenton reaction inside the cells of the body. All cells contain them, but when
these metals increase in concentration by even the most minimal degree, oxidative stress rapidly
ramps up. And as increased oxidative stress (where excess biomolecules are in the oxidized,
electron-depleted state) is maintained or even further increased, abnormal cell function
("disease") flourishes.

The oxidation stimulated by ionic iron (Fe3+, Fe2+) and ionic copper (Cu2+, Cu1+) remains
minimal ("physiological") as long as no significant new intakes of these metals occur, especially
when unwittingly supplemented. Most reasonably balanced diets will never supply too much of
these metals, although this delicate balance is easily disrupted by the most minimal of
supplemental intake.

The Fenton reaction plays a major role in the ability of the body to kill pathogens, pathogen-
infected cells, cancer cells, and cells with massively increased intracellular oxidative stress that
are on the border of necrosis and/or other forms of cell death like apoptosis. When not properly
balanced, it also plays a major role in the chronic toxicity inflicted by supplemental iron and
copper intake. Both metals are known as transition metals because they readily shuttle electrons
through various metabolic pathways. This ease of electron passage is why iron and copper
conduct electricity so well (current is electron flow).

The classic Fenton chemistry is seen in a pathogen-infected cell, especially when provoked by a
sufficient administration of vitamin C. While vitamin C has many different immune-supporting and
anti-pathogen properties, it is the promotion of Fenton chemistry inside the cell that likely
accounts most directly for its infection-resolving properties.

The most virulent of pathogens are the most avid consumers of iron. It is this characteristic that
literally allows most pathogens to self-target themselves since this iron excess so strongly fuels
the Fenton chemistry metabolism. Of note, some antibiotics owe much of their effectiveness due
to their ability to chelate iron, thereby weakening the pathogen as it loses access to new sources
of iron for its growth.

The following activities describe a typical Fenton reaction-fueled destruction of a pathogen and its
host cell:

50 or more grams of vitamin C is infused.

As the vitamin C floods the extracellular space, active and passive vitamin C transporters
increase vitamin C levels inside the cells.
At the same time in the extracellular space, the vitamin C continually stimulates the
formation of relatively large amounts of new hydrogen peroxide.
The hydrogen peroxide, which is already elevated inside the cell that is infected, with its
attendant focal hypoxia and acidosis, readily passes from the extracellular to intracellular
spaces
The vitamin C donates an electron to Fe3+ (or Cu2+), with a reduction to Fe2+ or Cu1+.
The reduced metal then donates an electron to the hydrogen peroxide that is present,
resulting in its prompt breakdown into a highly pro-oxidant entity known as hydroxyl
radical.
This radical is so reactive that it cannot migrate but immediately oxidizes whatever it is
adjacent to when it is formed.
Sustained formation of new hydroxyl radicals increases oxidative stress rapidly to the point
of pathogen/cell rupture and death.
Hydrogen peroxide inside the cell helps mobilize Fe3+ from ferritin storage ensuring
adequate reactive iron to fuel the Fenton reaction to completion.
Therefore, continued VC infusion assures that all components of the Fenton reaction are
sufficiently present to continue until pathogen/cell death has been achieved. No substrates
run out prematurely.

This interaction of vitamin C with copper (or iron), with the subsequent upregulation of the highly
pro-oxidant Fenton reaction, was nicely demonstrated in a study on mice. It was clearly shown
that the simultaneous administration of vitamin C and copper led directly to increased systemic
oxidative stress and kidney cell injury. [9] However, without the copper present, protection
against increased oxidative stress in the kidneys is readily achieved by vitamin C alone. [10]

It is well-established that both iron and copper play important roles as cofactors in various
metabolic pathways and enzyme reactions. However, the total pool of reactive iron and copper in
the body that plays these roles is extremely small, and it is almost completely maintained by an
ongoing recycling of these metals inside the cells. Very little of these metals gets excreted, and so
very little new intake is needed for them to perform these various metabolic functions.
Nevertheless, these two metals have a powerful negative synergy in causing pathology. A good
example of this is the elevated levels of both copper and iron that are found in human
atherosclerotic plaques. [11]

Relatively massive amounts of iron, and to a much lesser extent, copper, are needed to maintain
the normal synthesis of new red blood cells, compared to the very small amounts required for
their cofactor functions. A copper deficiency anemia is quite rare, but the iron deficiency anemia is
much more common. [12,13] However, the iron deficiency anemia rarely ever occurs without a
significant loss of blood, as can be seen with heavy menses or a bleeding gastrointestinal tumor.
The bottom line for patient management, however, is that when there is a normal hemoglobin and
a normal hematocrit, NO iron or copper should ever be supplemented. The ferritin level can never
be considered too low and a reason for iron supplementation if the hemoglobin level is normal.
Any such supplementation needlessly and reliably fuels excess oxidative stress throughout the
body.

Too much supplementation guidance comes from researchers that have found that agent X has
some effect on enzyme or protein Y, without any regard for the general health of the research
subject or the stability of serial blood examinations over time. Taking a "deep dive" on trying to
understand as much as possible about a supplement is fine, but the "macro" study should always
be given much greater regard than the "micro" study, especially when such "micro" studies are
taking place in animals or test tubes, and extrapolations are being made as to what supplement is
good for the entire human body.

A good example comes from some studies looking at the interactions between vitamin C and
copper. In rats it has been shown that increased dietary vitamin C increased blood levels of the
vitamin C while reducing the plasma and tissue concentrations of copper. [14] In another study,
both men and guinea pigs were supplemented with vitamin C. The supplementation increased
ceruloplasmin (copper-carrying protein) levels in the men while decreasing them in the guinea
pigs. The authors concluded that vitamin C has an antagonistic effect on copper metabolism in
guinea pigs but not in humans. [15] A cell study concluded only that vitamin C exerts both positive
and negative regulatory functions in copper metabolism, while stating that the mechanism is
unclear. [16]

When trying to make any sense of the advisability of copper supplementation after reviewing the
studies above, consider that the ability of vitamin C, at least in rats, to reduce the plasma and
tissue concentrations is a good outcome. Based on the ease with which added copper can
worsen oxidative stress, the ability of vitamin C to minimize its presence in the body can easily be
considered a good outcome, without just assuming that a chronic lowering impact on copper
presence in the body is not desirable. Linus Pauling started taking 3 grams a day of vitamin C as
soon as he learned of it in the 1960s, gradually increasing the amount until he was taking 18
grams a day the last years of his life. Dr. Pauling died at age 93, and he was clear enough of mind
to be giving lectures/speeches up to the last few months of his life. If Dr. Pauling was suffering
from a vitamin C-induced deficiency of copper in his body, there was no clinical evidence that
harm was being done. Quite the contrary, the loss of the ability of the human liver to make mega-
gram doses of vitamin C daily and release it directly into the bloodstream argues that any copper-
lowering effects of vitamin C are completely desirable, and that most of the human population is
dealing with some degree of copper toxicity already that is no longer being alleviated by the
missing endogenous production of vitamin C in the genetically-defective human liver. [17]

The consistent relationship between elevated copper levels and carcinogenesis should cause
grave concern for health seekers who regularly supplement copper. Many studies have
consistently shown that those individuals with the highest blood levels of copper contract, and
sustain, the most cancers. Also, just as cancer cells "feed" on iron, they also are fed by copper. It
appears that the continued presence of more copper is a major factor in both causing the initial
malignant transformation of the cancer as well as in fueling its aggressive growth and spread.
Tumor copper levels and blood copper levels are elevated in a wide variety of cancers, including
the following: breast, cervical, ovarian, lung, gastric, bladder, thyroid, oral, pancreatic, and in the
head and neck. [18-31] Furthermore, higher serum levels of copper are seen in more advanced
stages of cancer and are directly correlated to how readily the malignancy grows. [32] In some
hematological malignancies, periods of cancer remission are seen as serum copper levels
become lower. [33] And just as less copper can induce cancer remission, more copper can be
given as oxidation-inducing "chemotherapy" to push the already increased intracellular stress
(Fenton reaction) even higher, with cancer cell death eventually resulting. [34,35]

Always look for the longevity (all-cause mortality) studies to get the clearest picture of the ultimate
impact of an agent on the human body. The impact that something has on isolated metabolic
functions in the cytoplasm is often completely irrelevant (the "accumulation of minutia," as Dr.
Robert Cathcart once noted) if it argues against taking a supplement by itself after such a
supplement was already proven to decrease all-cause mortality. And this is even more the case
when it is an animal or in vitro study. As Dr. Abram Hoffer once noted, studies can make good
scientific points while still remaining "clinically unimportant."

Furthermore, such "micro" data should never be used, intentionally or unwittingly, to strike fear
into the hearts of potential supplementers of a clearly beneficial agent, such as vitamin C. It has
been long-established now in "macro" studies that individuals who maintain the highest blood
levels of vitamin C live the longest. [36,37] In the face of such data, if vitamin C truly does work to
lower copper levels in the body, then that would appear that such an effect is highly desirable and
the only long-term effect of chronic high doses of vitamin C on copper levels would be keeping
them less elevated, but never causing widespread deficiencies. Furthermore, such data also
supports the concept that truly copper-deficient individuals, except under the most extraordinary
of circumstances, do not exist. The clear-cut conclusion is simply this: never supplement
copper.

Iron, a transition metal like copper, reliably increases oxidative stress wherever it is found in its
free, unbound state. Much, perhaps most, of this increased oxidative stress from iron results from
an upregulation of the Fenton reaction throughout the body. While body-wide copper excess is
easily inferred in nearly everyone from the data discussed above, it is not as easy to clearly
establish the presence of such an excess through blood testing. On the other hand, excess iron in
the body is reliably reflected in the ferritin blood test. [38,39] Ferritin is an intracellular protein that
stores iron, releasing it from storage as needed by the body. Higher ferritin levels indicate high
iron content in the body, although certain conditions, often inflammation secondary to acute
infections, will increase the numbers on this test while still not reflecting increased amounts of iron
in the body. This occurs since ferritin is an acute phase reactant, representing a leakage product
from damaged and dying cells. [40] Severe infections can result in astronomical elevations in the
ferritin level, as in advanced COVID patients. [41]

While perhaps counterintuitive, serum iron levels have little to no correlation with the amount of
excess iron stored in the body. However, as more unbound ("free") iron enters the body in excess
of the amount of iron needed to sustain normal metabolic needs, the more the synthesis of ferritin
is stimulated, and the excess iron is promptly stored inside the shell-like structure of the ferritin
molecule. Not surprisingly, as free iron is a common culprit in stimulating excess oxidative stress,
the presence of extra oxidative stress itself results in the synthesis of more ferritin, allowing the
excess pro-oxidant free iron to be removed from the involved tissues. [42] Higher ferritin levels not
only indicate increased stores of iron in the body, they also indicate an ongoing attempt by the
body to synthesize enough ferritin to keep extracellular and intracellular levels of free iron at
nontoxic levels. When free iron is very minimal, ferritin levels can drop very low, since they
primarily needed as a buffer against excess iron presence.

Iron excess is so pandemic around the world (except for extremely malnourished third world
countries) that the LabCorp laboratory reference range for ferritin is 30 to 400 ng/mL. The
reference range for any laboratory test makes the basic flawed assumption that most individuals
in a group will have a normal result and that the reference range will serve to contain the majority
of normal individuals in a given population. However, when a condition or deficiency affects nearly
everyone being tested, the reference range has no direct bearing on normalcy at all. As will be
shown, the LabCorp ferritin reference range actually encompasses NO normal levels, as any
ferritin measurements above 25 ng/mL mark the beginnings of excess iron accumulation. The true
"normal" range for ferritin, which is seen mostly in children and younger menstruating females,
runs roughly from 15 to 25 ng/mL, although lower levels can still be normal when no anemia is
present.

A ferritin level of 50 ng/mL is considered to be normal by many physicians, with some of them
even regarding such a level as being too low. Phlebotomy (blood donation) has been clearly
established to reduce iron stores in the body and lessen laboratory parameters of lipid
peroxidation and oxidative stress, decreasing the incidence of heart disease in the process. [43-
45] Studies looking at reduced iron stores after blood donation show that ferritins of 50 ng/mL,
while not drastically elevated, nevertheless are clearly associated with a deterioration of an
important vascular function. The ability of the blood vessels to dilate (or relax) normally was
shown to be clearly better in blood donors who averaged ferritin levels of 17 ng/mL versus those
with ferritin levels at 52 ng/mL. [46] A similar finding was seen in another study comparing the
ease of arterial dilation with ferritin levels reduced well below 50 ng/mL. [47] Loss of easy dilation
is an early finding in patients who develop atherosclerosis and other vascular conditions. Any
increases in cellular or circulating free iron quickly increases oxidative stress, which is the primary
reason for the endothelial dysfunction and the impaired vascular relaxation. [48,49]

The relationship between heart disease and increased ferritin levels is especially well-established.
In both men and women, elevated serum ferritin is both independently and positively associated
with coronary artery disease. [50-52] Even a greater incidence of heart disease is seen in men
and postmenopausal women compared with the incidence in premenopausal women, as the
regular loss of blood (and iron) stops at menopause. [53]

A similar reduction in the incidence of new cancers and cancer-related deaths is seen with serial
phlebotomies over a six-year period. The average ferritin level in 23 individuals dying of cancer
was 136 ng/mL, while the 77 survivors had an average ferritin level of 84 ng/mL. [54] Another
study revealed that reducing iron stores by phlebotomy clearly reduced risk of cancer and cancer-
related mortality. [55] As it turns out, the serum levels of all three of the toxic nutrients (calcium,
iron, and copper) are significantly increased compared to levels in non-cancerous control patients.
[56]

Now for the shocker. Since the 1940s the routine "enrichment" of flours, cereals, and grains with
iron (along with some B vitamins) began on the premise that the wartime populations of the
United States and the United Kingdom were being rationed food and the overall availability of
some important nutrients were felt to be lacking. In 1942, the U.S. Army decided to purchase only
flour that was enriched. This quickly led to much of the world following in lockstep with the United
States. And once it started, it never stopped, continuing to this very day.

One big problem with this is that nobody in the United States eating even the most faddish of
diets has an iron deficiency, and no additional iron of any kind does anything but inflict body-wide
oxidative damage to the consumer. The second problem is that the form of iron being added much
of the time to these enriched foods is in the form of metallic iron filings. Somehow our public
health authorities have decided that eating pure metal is the best way to keep from developing
deficiencies in compounds related to that metal in the body. Obviously, for the ingestion of iron (or
any other metal that forms different compounds), the iron/metal must first be metabolized in a
plant to produce consumable forms of that metal. Bear in mind that any form of additional iron is
not good for you, but consuming iron in its metallic form is especially effective in causing the daily
oxidative stress exposure in the gut to skyrocket. As a picture is worth a thousand words, and a
video worth even much more, please take a few minutes to view this brief video, filmed roughly 30
years ago now (and nothing has changed since, as it is very easy for anyone to reproduce it).
https://www.youtube.com/watch?v=HGbwFtmJOi4&t=75s

The only time iron should ever be deliberately ingested (and in a proper medical formulation,
never as an unrefined metal!!) is when a low ferritin is seen AND a hypochromic, microcytic
anemia (pale and small red blood cells) is present. And once the hemoglobin level is back to
normal, the iron prescription should be stopped. Iron should never be taken to "protect" against
developing an iron deficiency anemia. Excess blood loss, whether from excess menses or a loss
of blood from a gastrointestinal tract cancer, is nearly always the reason for the presence of a low
ferritin and a hypochromic, microcytic anemia. And while a nutritional deficiency of iron is very
common in third world countries, it is exceptionally rare in the United States. [57] Short of frank
chronic starvation, dietary iron deficiency simply does not exist.

Incredibly, some of this outrage over adding metallic iron filings might finally be filtering back to
the governmental agencies in charge of continuing this process, as the internet now has websites
that discuss "food grade" iron filings, as if the consumption of "contaminated" iron filings is the real
problem. Some misguided pundits assert that the acid in the stomach dissolves the metallic iron
and allows it to be absorbed and assimilated. However, basic chemistry does not support such an
assertion. Metallic iron + HCl (hydrochloric acid) converts to ferric chloride, a form of iron that is
exceptionally toxic, corrosive, and acidic. [58,59] Supplemental iron commonly used is in the form
of ferrous sulfate, not ferric chloride.

As all disease results from the excess oxidation of biomolecules, it can readily be appreciated
how negative the ingestion of metallic iron filings will be on overall gut health and function,
especially when it is done for a lifetime. No substance promotes excess oxidation wherever it is
found more than free iron in its ferric form. When ingested chronically in its metallic form, it can
directly cause a foreign body reaction when the metal fragments are large enough. Furthermore,
as more ferric chloride is formed from the HCl in the stomach, the stage is set for the nonstop
provocation of chronic inflammation in the gut. This can manifest itself clinically in just about all
forms and presentations of gut dysfunction, including leaky gut and a pathogen-overgrown
microbiome. Of note, Helicobacter pylori, the pathogen now considered to be the causative agent
for many cases of ulcer disease in the stomach and small intestine, thrives optimally where iron is
most plentiful. [60,61]

Food allergies were largely unheard of before the widespread poisoning of enriched food with
metallic iron filings. As of 1971, about 100 articles addressing food allergy were published on
PubMed. Now, in 2023, the phrase "food allergy" yields over 12,000 articles. Nearly all of this can
be blamed on the widespread presence of the leaky gut syndrome, for which the incessant
ingestion of metallic iron can be considered a major cause. Peanuts and gluten contain proteins
that digest well when the gut is intact. However, when undigested segments of peanut or gluten
protein make their way into the lymphatics and blood, severe allergic and autoimmune reactions
are to be anticipated. In the 1950s and 1960s a peanut butter and jelly sandwich was never the
potentially fatal snack that it is today for so many children.

For many adults today, their iron assault began in infancy. For many reasons breast feeding is the
healthiest way to feed a newborn. However, when electing to bottle-feed, realize that it is
extremely difficult to find an infant formula free of added iron. The ingestion of this excess iron
from the start of life is a major reason why so many people have never had a truly normal, well-
formed bowel movement in their lives. Supermarkets and drug stores offer a massive array of pills
and potions for every conceivable bowel/digestive problem, a clear visual reminder of how
widespread digestive disorders are.

One of the reasons that organic and gluten-free food products are supportive of good health is
that they do not have iron added to them. At least, that is the case with probably 90% or so of
them. The ingredient labels still need to be carefully read, since even these food products are
occasionally contaminated with extra iron as well.

Many factors play a role in achieving and maintaining good gastrointestinal health, which is
incredibly important as compromised gut health negatively impacts any other medical conditions
throughout the body. A major step toward good gut health throughout the population will be taken
when metallic iron filings are no longer a regular part of so many diets throughout the United
States and the rest of the world.

Recap

Most vitamins, minerals, and other nutritional supplements can be pushed to very high degrees of
intake without resulting in any significant clinical toxicity. However, this is not always the case, and
it is very important to be aware of the circumstances under which minimal added intake of some
supplements can be devastating to achieving and maintaining long-term health.

Except under the very limited scenarios described above, calcium, iron, and copper should never
be supplemented. And in the case of calcium, a high daily intake of some dairy products can be
very harmful as well. All three of these "toxic nutrients," while absolutely necessary at low levels
for the health of all cells, rapidly become major weapons in bringing down the health of those
same cells with only MINIMAL degrees of added intake.

Iron intake is especially problematic, as so many people are getting continually "supplemented"
with iron, typically in the form of metallic iron filings, whenever they eat any of a large variety of
common foods.

All three of these nutrients are some of the most common, yet still almost completely
unrecognized, causes of death by heart disease and cancer.

(Author of this article, Dr. Thomas Levy can be contacted at televymd@yahoo.com)

(The views expressed in this article are the author's and do not necessarily reflect the opinions of
the Orthomolecular Medicine News Service or all members of its Editorial Board. OMNS invites
alternative viewpoints. Submissions may be sent directly to Andrew W. Saul, Editor, at the email
contact address further below.)

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