Toxic Iron and Ferroxidase, the Master Antioxidant

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In modern times, we have lost traditional wisdom and lost our resiliency to disease. In line with Occam’s razor (“All things being equal, the simplest solution tends to be the best one”), I believe that one of the principal com­mon denominators responsible for our lack of resiliency is toxic iron. Many people have too much iron in their body, and that iron lacks an excretory pathway, making us more susceptible to stressors and compromising our ability to heal.

Obviously, iron is important; we especially need it to deliver oxygen. Eighty percent of our iron is in hemoglobin, the protein component of red blood cells, which carries the oxygen to the cells. However, as Paracelsus said, “The dose makes the poison.” In the wrong form, the wrong dose or, most importantly, if it’s not properly escorted, iron is highly toxic. Iron must be properly chaperoned around the body, and when it’s not, it will react with oxygen in a negative way and “rust” you from the inside out. Those who eat a standard American diet (SAD)—full of iron-fortified foods—for any period of time are likely to end up with excess iron; and the SAD tends to create deficiencies in copper and vitamin A, which are needed to recycle the iron appropriately.

LOST WISDOM AND LOST RESILIENCY

Before I discuss iron further, let’s consider the traditional wisdom that we have lost—wisdom that I believe to be divine in origin. In Nutrition and Physical Degeneration, Dr. Weston A. Price discusses the Indians of the Yukon (pages 279-80), describing how white prospectors eating canned foods died of scurvy, thought “[a]ny Indian man or woman, boy or girl could have told [them] how to save [their] life by eating animal organs or the buds of trees.” Dr. Price also recounts the story of an engineer-prospector who “nearly went blind with so violent a pain in his eyes that he feared he would go insane.” The cause (though he did not know it) was vitamin A deficiency. One day, while weeping “in despair of ever seeing his family again,” he encountered an old Indian who recognized the problem. After catching a fish, the Indian “threw the fish out on the bank and told the prospector to eat the flesh of the head and the tissues back of the eyes, including the eyes, with the result that in a few hours his pain had largely subsided. In one day his sight was rapidly returning, and in two days his eyes were nearly normal.”

Of course, modern science has since estab­lished that animal foods—and particularly the tissues in back of the eyes—are one of the rich­est sources of vitamin A. However, the reason I share Dr. Price’s stories is to underscore the fact that we’ve lost wisdom that we urgently need. Consider what the U.S. health picture looks like today. Compared to other wealthy nations, U.S. infant mortality and life expectancy are both rock bottom—more of our babies die, and Americans as a whole die younger than those from other wealthy nations. American children now “are destined to live shorter lives than [their parents].”¹

When it comes to the percent of the popula­tion over age sixty-five with two or more chronic diseases, we’re number one. Autoimmune diseases, obesity and cancer have skyrocketed. As Bloomberg put it a couple of years ago, Americans are “retiring later, dying sooner and sicker in-between.”² Equally worrisome, a study of millennials (born in the 1980s and 1990s) released by Blue Cross Blue Shield in April 2019 showed that millennials’ health starts declining by age twenty-seven.3 Compared to what the previous generation (born in the 1960s and 1970s) faced at the same ages, millennials experienced double-digit increases for eight of ten health conditions from 2014 to 2017.³

This dismal picture is not for lack of medi­cal intervention. The U.S. spends more on health per capita than any Organisation for Economic Co-operation and Development (OECD) coun­try and leads the world for performance of MRIs, CT scans, tonsillectomies, coronary bypasses, knee replacements and caesarean sections.⁴ Compared to other countries, Ameri­cans also rely more on medication.⁵ After age twenty, it’s essentially normal to be on multiple medications.⁶ In short, we spend a whole lot of money, we do a whole lot of interventions, we go to the doctor the most—and we get the worst outcomes. The current system is failing.

BEYOND SYMPTOM MANAGEMENT

Both of my grandfathers were small-town country doctors who could do everything from deliver babies to fix broken bones. I went to medical school because I wanted to be like them. However, my training taught me that patients experiencing symptoms had only two options: take a drug or continue to suffer. I didn’t un­derstand that there was a third option—address the root cause.

In my early years of practice, I perfected the seven-minute visit and the art of billing. With high patient volumes and reimbursement rates, I helped my county pay off a one-million-dollar clinic within a year. Things were going so well that the clinic even got written up in The Washington Post. I thought I was living my dream as a small-town family doctor. But there was one problem: no one was getting better, and that bothered me.

Looking for answers, I met an integrative doctor who told me that there is no such thing as “disease,” only “consequences” and inflamma­tion. After I sent him ten of my sickest patients and they all came back better, our clinic began focusing on going after “bugs” and toxins: Candida, mold, heavy metals, glyphosate and more. (In the U.S., the list of potential toxins is long: Over eighty thousand different chemicals are registered for use, but almost none has been assessed for safety.⁷)

Even with this improved approach, how­ever, something was still missing. Lowering inflammation was helping some patients feel and do better, but others were not getting all the way better or would get better only to get worse again. At that point, I began studying how our medical system’s commitment to Pasteur’s germ theory had taken us off course. (Consider that deaths from drug-resistant “superbugs” are expected to become the top cause of death by 2050.⁸) I became interested in Claude Ber­nard’s terrain theory, and when I read Suzanne Humphries’ book Dissolving Illusions: Disease, Vaccines, and the Forgotten History⁹ —showing the dramatic decline in infectious disease rates well before the introduction of vaccines—and Dr. Tom Cowan’s book on vaccines and autoim­munity,¹⁰ it became even clearer that it really is the terrain that matters.

I also began learning how epigenetic factors can turn genes on and off and affect mitochon­drial functioning. Factors that we know can have epigenetic effects include the gut microbes, movement (sitting has been called “the new smoking”), hydration, nature and even one’s thoughts. The amazing book by Richard Louv, Last Child in the Woods,¹¹ proves how power­ful it can be just to get outside. Or consider the importance of circadian rhythm: Dr. Satchin Panda’s book The Circadian Code shows that something like fifty chronic diseases begin to affect rats when you feed them on a schedule that disrupts their circadian rhythm!¹² My practice started focusing on what I call the “four pillars of health”: nutrition, hydration, movement and peace.¹³

THE CELL DANGER RESPONSE

Over the past decade, San Diego researcher Dr. Robert Naviaux and his colleagues have refined a theory—dubbed the “cell danger response” (CDR)—that defines the healing cycle in metabolic terms.¹⁴ The theory posits that “most chronic illnesses are caused by the biological reaction to an injury, not the initial in­jury or the agent of the injury.”¹⁵ In other words, metabolic dysfunction drives chronic disease, and “illness occurs because the body is unable to complete the healing process.”¹⁵

One of the important observations un­derpinning the CDR is that the mitochondria “change their function rapidly under stress,” with pro-inflammatory M1 mitochondria serv­ing a “battleship function” and anti-inflamma­tory M2 mitochondria serving a “powerplant function” (see figure below).¹⁴ When a cell senses a stressor, it flips into M1 to deal with that stressor, increasing free radicals and decreasing energy production. Next, the cycle is supposed to transition into M2, with energy increasing and oxidative stress going back down.

This cycle probably worked well with the types of stressors encountered in Dr. Price’s day (such as infectious diseases and trauma) but is less suited to today’s continual onslaught of toxic exposures—pesticides, heavy metals, wireless radiation, processed foods and so on. The Naviaux group’s insight is that in the face of modern stressors, the CDR can get “stuck” in M1, meaning that “cellular equilibrium is altered, preventing completion of the healing cycle and permanently changing the way the cell responds to the world.”¹⁵ Even when the threat has passed, “cells behave as if they are still injured or in imminent danger.”¹⁵ And when free radicals run wild, they can damage the cell membrane, mu­tate DNA and wreak all kinds of havoc. When the natural healing cycle escalates into and gets stuck in this type of oxidative stress storm, we get epidemic levels of chronic disease (see below).

Another way to understand the CDR is to think of the mitochondria as the carburetor. A carburetor needs fuel (glucose or fat) plus oxygen from what we breathe plus minerals that act as the spark plug (mostly magnesium and copper) to produce energy (ATP), but in the process, it also produces “exhaust” (free radicals). If you think of a cell as needing to be able to clear out this “exhaust,” we might say that when the CDR is stuck in M1, it’s because something is “gunking up” the carburetor.

MINERAL IMBALANCES AND METABOLIC DYSFUNCTION

The next pivotal phase of my learning curve came when one of my patients whose healing had reached a plateau experienced improvement after implementing some of the elements of Morley Robbins’ Root Cause Protocol (see sidebar, next page).¹⁶ I was so interested in this patient’s outcome that I called Morley to learn more about the protocol, and I have been using it ever since. Morley’s perspective, compatible with the CDR, is, “There’s no such thing as disease, there’s only metabolic dys­function caused by mineral imbalance”—and specifically, iron, copper and magnesium.

There are several types of iron. Heme iron, in animal meat, is more easily absorbed than the non-heme iron in dairy, eggs or plants. However, when you eat heme and non-heme iron and you have the right mineral balance otherwise, things tend to be in balance. A 2001 study address­ing the safety of iron in our food showed that “homeostatic mechanisms increase intestinal iron absorption in iron deficiency.”¹⁷ What that means is if you’re low in iron, your body has the amazing intelligence to absorb more. Unfortunately, the reverse is not true: iron’s “down-regulation at high intake levels seems insufficient to prevent accumulation of high iron stores at high intake” and “there is no regulated iron excretion in overload.”¹⁷ In short, when you need more iron, the body can upregulate, but when you put too much in, the body is not very good at downregulating, and you will end up with excess iron.

As already mentioned, 80 percent of our iron is in the red blood cells. A red blood cell lives about ninety to one hundred twenty days and then dies. When red blood cells die, the body is able to recycle twenty-four of the twenty-five milligrams (mg) of daily iron that the red blood cells need. We need only about one mg per day in dietary intake to replace the minimal amount lost in the stools, urine and through sweating. Without a mechanism for the active excretion of iron, ongoing uptake of excessive iron will result in iron deposition in the brain, joints, liver and various tissues.¹⁸

It’s a problem, therefore, when you throw a bunch of iron-fortified foods into the diet (see Table 1). Consider an iron-fortified product like Cheerios, which contains seventeen milligrams of iron in just one cup. (And who eats just one cup of Cheerios?) In a 1993 book called Iron Deficiency Anemia,¹⁹ the authors described how most dry infant cereals are fortified with a “metallic iron powder”—iron filings—and a Chinese study published in 2016 showed that this excess iron in baby food increases inflam­mation. When poor rural toddlers in China were fed either an iron-fortified cereal, a non-fortified cereal or meat, the iron-fortified group expe­rienced a high rate of systemic inflammation “likely to impair their growth.”²⁰

The Chinese authors claimed that the forti­fied cereal improved the toddlers’ anemia, but their indicator for anemia (ferritin) was not an appropriate measure. Ferritin is an intracellular storage compartment for iron, and—accord­ing to Sir Douglas Kell, the world’s foremost authority on ferritin—it should be in the cell, not the blood; if it is in the blood, then it’s been extruded out of the cell because the cell is full.²¹

IRON OVERLOAD AND DISEASE

In 2010, a researcher pointed out that iron levels “must be tightly regulated to provide an essential nutrient that is involved in oxygen delivery, metabolism and redox regulation while guarding against excessive levels of a primary toxicant that can generate reactive oxygen species (ROS) to produce cellular dam­age and death.”²² What is noteworthy about that statement is the description of iron as both an “essential nutrient” and a “primary toxicant.” As the researcher also noted, “A large body of clini­cal evidence demonstrates disease susceptibility and the response to inflammation and infection worsen with elevated iron stores,” with a par­ticularly well-documented relationship between iron overload and infectious diseases.²² Interest­ingly, the reverse also seems to be true, with iron deficiency conferring “relative resistance to infection.”²² As a 2004 review article titled “Is stored iron safe?” observed, “Antioxidant and antiinflammatory processes may operate optimally only in the absence of stored iron” [emphasis added].²³

Iron status not only affects susceptibility to infectious diseases but also profoundly in­fluences risk factors for inflammatory chronic diseases such as diabetes,²⁴ obesity, metabolic syndrome, atherosclerosis, neurodegeneration,²⁵ liver disease and many other conditions (see Table 2). Researchers view this as significant because of the potential for “simple preventive or therapeutic avenues” such as modified dietary iron or therapeutic phlebotomy [blood letting].²² Iron accumulation in various brain regions is associated with central nervous system (CNS) disorders such as Alzheimer’s disease, Parkin­son’s and multiple sclerosis.²⁶ Autoimmunity, too, correlates with excess iron. Researchers have observed iron-laden macrophages in nu­merous autoimmune conditions.²⁷ When the macrophages (ordinarily the “Pac-men” of the immune system) are full of iron, they become dysfunctional and turn the immune system against the body.

Excess iron is a risk factor for cancer be­cause iron works as a catalyst for a chemical reaction that produces highly toxic hydroxyl free radicals that can potentiate tumor forma­tion.²⁸ In fact, cancer cells “exhibit an enhanced dependence on iron relative to their normal counterparts,” a phenomenon that some re­searchers have termed “iron addiction.”²⁸ In one study, German researchers detected five times more iron in breast cancer tissue than in normal tissue.²⁹

To summarize thus far, excessive iron with­in cells is a “potent driving force” for oxidative stress and inflammation.³⁰ Research describ­ing the “danger sensor” of the cell (something called the NLRP3 inflammasome) clarified that it is an unbound or “free” form of iron that is of particular concern.³¹ This form of free iron, called cellular labile iron, pulls the trigger on the inflammatory cascade. Framed in terms of the cell danger response, free iron gets M1 “stuck” and chronically “on.”

THE ROLE OF COPPER

Copper and iron have an intertwined relation­ship.³² Copper is integral to the metabolism of iron and facilitates iron absorption, iron transportation, the re­lease of iron from storage and the incorporation of iron into the hemoglobin. Copper also assists with blood coagulation, blood pressure control, cross-linking of connective tis­sues, CNS myelination, energy transformation, reproduction, hormone synthesis and more.³³

Iron and copper are the only two metals in the body that can deal with oxygen. While iron delivers oxygen to the cells, it is copper (in the form of copper-based enzymes or copper-influenced enzymes) that activates the oxygen in the mitochondria to make usable energy. Think of iron as being like the steel beams in a building, while copper is like the copper wiring delivering electricity. In other words, iron is structural, and copper is functional.

It can also be helpful to think of the copper-iron relationship like a square dance; the copper is the caller, and the iron (the dancer) has got to keep moving (getting recycled) all the time. If there is just a little extra iron, that’s okay because we’ve got a storage mechanism. We can store a little bit in case we need to grab some out of stor­age and make more red blood cells. However, we need only to store a little, and mostly, we need to be recycling it.

After iron enters a cell and does what it needs to do, it needs to shuttle out and be recycled. That shuttle is dependent on an important enzyme called ferroxidase, which also governs iron storage. If ferroxidase isn’t working, and can’t shuttle the iron out to recycle or store it, where is the iron going to go? The answer is the “metabolic sink”—your mi­tochondria—and it’s going to mix with oxygen. At that point, the oxidative free radical cascade that we have been discussing is going to ensue.

Acting as a ferroxidase, an important metal-binding protein called ceruloplasmin is the major copper-carrying protein in the blood. Each ceruloplasmin molecule contains eight atoms of bioavailable copper. One indicator of ceruloplasmin’s importance is the fact that it contains one thousand forty-six amino acids; by way of comparison, insulin has fifty-one. With adequate bioavailable copper, ceruloplasmin performs twenty-four known functions in the body, most importantly the management of iron. As discussed, this includes moving iron in and out of the cells, storing iron and building hemoglobin.

Remember my comments about the im­portance of getting rid of cellular “exhaust”? Bioavailable copper is what activates the ferroxidase enzymes that clear out your “ex­haust.” When the copper is not available, the ceruloplasmin can no longer function as a fer­roxidase—and if it’s not doing the ferroxidase job that it is supposed to do, you lose resiliency and develop major problems.

Modern factors that drive copper out in­clude high-fructose corn syrup, antibiotics, oral birth control methods, synthetic vitamin D and synthetic vitamin C (ascorbic acid). You should avoid them. Dietary copper can also be lacking due to demineralized crops and the absence of organ meats in the diet. There is twice as much copper in liver as iron, so eat your liver! Whole-food vitamin C is another source of bioavailable copper, as is high-quality bee pollen (which also is rich in other trace minerals). Beware of copper supplements; the copper is not bioavailable, and the body will have a very hard time using it.

RESTORING RESILIENCE

Excess iron and a lack of bioavailable cop­per will feed the “bad bugs” and shut down de­toxification enzymes, cellular energy production and cellular “exhaust” clean-up—thereby “rust­ing” you from the inside out. A primary strategy for restoring resilience, therefore, should be to ensure adequate bioavailable copper so that ceruloplasmin can carry out its designated fer­roxidase function.

There are both “stops” and “starts” involved in restoring an appropriate iron-copper balance. In terms of “stops,” individuals eating a Wise Traditions diet are probably already several steps ahead, because they know enough not to eat processed, iron-fortified foods or ingest synthetic supplements. If further tweaking is needed, the Root Cause Protocol is a helpful resource. In fact, many patients—even those who have been committed to a Wise Traditions diet for years—have told me that the Root Cause Protocol and the information about toxic iron were “missing links” in their quest for improved health and that they started to feel better once they started addressing their mineral imbal­ances. The Root Cause Protocol is not a silver bullet, but it seems to be a helpful approach that a lot of people have overlooked.

A recommended “start” is to get the iron out by periodically donating blood. (For women, this may be something to consider only after menopause, as menstruation is a natural form of iron release. However, reproductive-age women who have a high consumption of iron-fortified foods can still accumulate excess iron.) Practi­tioners who understand toxic iron will be happy to prescribe therapeutic phlebotomy. However, you don’t need a doctor’s order—just go and donate blood. Heart disease researchers have identified regular blood donation as an effective intervention for lowering cardiac risks linked to excess iron, even in the absence of any other measures.³⁴ Intermittent fasting, according to Morley, can also be helpful. On the other hand, iron chelation appears to be only minimally helpful.

One element of the iron story I have not yet discussed is the importance of vitamin A (retinol). Retinol is the backbone of the ferroxi­dase enzyme that is so critical for chaperoning iron, and retinol loads copper into ferroxidase. Interestingly, studies of anemia have illus­trated vitamin A’s importance.³⁵ Although we measure anemia via hemoglobin, adding iron does not meaningfully restore normal hemo­globin levels—but vitamin A does. In addition to high-quality cod liver oil, good sources of retinol include liver, pastured eggs and butter (preferably from raw milk).

As an interesting historical footnote, the observation in the 1940s of an association be­tween anemia in pregnancy and lower levels of hemoglobin was one of the factors that launched iron fortification of food. Reflecting the lack of traditional wisdom characteristic of our era, nutritionists and food scientists imposed this measure not just on the 1 percent of the general population represented by pregnant women but on everyone. In 1995, a study showed that the reasoning about hemoglobin and anemia was flawed; analyzing over one hundred fifty-three thousand pregnancies, the researchers found that not only is it normal for hemoglobin to go a little lower during pregnancy, but that failure of hemoglobin to fall below a certain level actually increases the risk of poor outcomes such as low birth weight and preterm delivery.³⁶

As Weston A. Price Foundation members know, twentieth-century changes in agricul­ture—mechanized farming, ammonium nitrate fertilizers, pesticides and herbicides including glyphosate—have had a profound impact on the availability of minerals in soil and food. Copper depletion has been particularly significant.³⁷ It currently takes twenty-one apples to provide the same amount of copper contained in two 1950s apples, and fifteen cabbages at present to furnish the copper in a single mid-twentieth-century cabbage. Interestingly, bronze farm tools (made up of 92 percent copper) are known to produce better results (in terms of magnetic frequencies in the soil and microbial balance) than iron tools.

PEACE

The fourth pillar of health—peace—is also fundamental. Most practitioners can attest to how often we see fear, stress and unresolved emotional conflicts as underlying triggers for health problems. When you lack peace, your ability to be resilient is highly compromised. At a metabolic level, stress causes our electrolytes to shift, and when that shift produces changes in pH, iron goes into the cell, magnesium goes out and metabolic chaos follows. Stress also grabs copper and essentially makes it unusable. A patient once told me, referring to the other three pillars of health (nutrition, hydration and movement), “I’ve done all that, but I need to get my stress in check.” This person knew that nothing will work when stress levels are chroni­cally up. I would add that while there are many options available to “manage” stress—and that can be helpful for a time—ultimately, you need to address the root causes in the same way that you would do for a physical condition. True peace is a foundational component to building resiliency.

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SIDEBARS

THE ROOT CAUSE PROTOCOL
The steps of the Root Cause Protocol (which many have used to reverse autoimmune conditions successfully like
Lyme disease, Hashimoto’s thyroiditis, fibromyalgia) involve learning to feed your body the correct nutrients and supplements in order to balance magnesium, copper and iron—and repair cellular dysfunction. The protocol involves “stops” (such as not taking iron supplements) as well as several phases of “starts” (therootcauseprotocol.com/about/). Currently, 72 percent of pregnant women and 60 percent of lactating women in the U.S. take an iron-containing supplement.³⁸

STOPS:
• Do not eat a lowfat, high-carb, processed, refined-foods diet. Avoid high-fructose corn syrup, synthetic sugars and
industrialized omega-6 oils such as soybean and canola oils.
• Avoid (or stop taking) the following supplements: iron, vitamin D3, calcium, zinc, molybdenum and “drugstore”
multivitamins and prenatal vitamins.
• Avoid synthetic forms of ascorbic acid, citrate and citric acid.
• Stay away from fluoride (in water, toothpaste, etc.)
• Do not use colloidal silver as an antibiotic.

STARTS:
• Phase 1: Eat organic whole foods; take mineral drops, magnesium, whole-food vitamin C and vitamin E complexes,
cod liver oil and an “adrenal cocktail.”
• Phase 2: Obtain natural B vitamins from bee pollen, stabilized rice bran and beef liver (preferably all three).
• Phase 3: Take silica (diatomaceous earth) and boron, taurine and iodine supplements.
• Phase “X”: Donate blood; get more sunlight; do “joyful movement”; clear food and environmental sensitivities;
learn to use the Emotional Freedom Technique (EFT); limit exposure to blue light radiation.

ASSESSING IRON OVERLOAD
Standard tests assess the amount of iron in the blood. However, even if a blood test shows iron levels to be “normal” or “low,” iron in the blood does not equal iron in the tissues—and the tissues may well be iron-saturated. There is a combination of blood tests that doctors can do to get more of a read on iron overload, but one has to know how to interpret them correctly, and most doctors don’t have that knowledge.

The ideal test would be an easy-to-use and easy-to-understand test for the ferroxidase enzyme. At some point, a test like that may become available. In the meantime, I use patient history to evaluate iron overload. If patients have eaten the standard American diet for any number of years or decades, then—unless they are experiencing extensive bleeding for some reason (such as with very heavy menstrual cycles or ulcerative colitis), I’m going to assume that they are high in iron.

REFERENCES

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This article appeared in Wise Traditions in Food, Farming and the Healing Arts, the quarterly journal of the Weston A. Price Foundation, Fall 2020

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