1. Are you sensitive to fragrances and odors?
2. What about food—any sensitivities?
3. Sensitive to particular medications?
4. To alcohol?
5. Do you get a bad reaction from monosodium glutamate in food?
6. Do you have sensitivity to caffeine?
7. Have you ever been sick from exposure to chemicals?
8. Does cigarette smoke bother you or make you sick?
9. Are you sensitive to smog or air pollution?
10. Do you sometimes wake up in the morning feeling as if you’ve been drugged?
11. Ever have unexplained skin rashes?
12. Do you ever experience brain fog?
13. Do you feel a tingling in your hands or feet?
14. Is there consistent ringing in your ears?
15. Do you experience unexplained muscle pain?
The office coffeepot keeps perking all day long. Alan allows himself half a cup when he arrives at eight o’clock in the morning, and it wires him for the rest of the day. Sue, in the next cubicle, drinks cup after cup all day long and remains as calm and unruffled as a stone statue of the Buddha.
On the other hand, Sue’s head hurts on the rare occasions when she indulges her passion for chocolate. Alan can eat a ton of chocolate, but a single glass of red wine will send him to bed with a crashing headache; he’ll occasionally drink a glass of white wine but mostly just avoids the grape.
His wife, Barbara, can eat and drink anything without feeling the slightest effect, but after Alan sprayed the house to get rid of the mosquitoes that fly in because the kids don’t close the screen door tightly, Barb’s whole body was suddenly covered in red welts. It took a trip to the emergency room and a hit of steroids to calm the reaction.
While they were in the ER, a man was brought in on a gurney suffering even more than Barb. His affliction? An adverse reaction to acetaminophen, of all things; the guy had taken your basic over-the-counter Tylenol, and next thing he knew, he was flat on his back in an ambulance. Yet the physician attending to Barb told them the ER got more visits for this than for an adverse reaction to any other drug.
Why? What’s going on? Why do our bodies respond to different things in the environment in these ways—and why are the responses so individual and so varied? The answers are to be found in the core process we call detoxification. The process is kicked off by the natural physiological reaction of all organisms to reject “foreign” things that may be toxic—that is, things the organism senses don’t belong to it and may be harmful to it in some way. The term for such things is xenobiotics—from the Greek xenos, meaning “stranger,” and bios, meaning “life.” What makes the process tough to figure out is that what seems foreign and toxic to one organism may not seem so to another organism, which is why Alan and Sue have such drastically different physical reactions to a simple substance like coffee. What we can say, however, is that each individual’s personal detoxification response to one or another specific substance is tied to both the individual’s genetic heritage and his or her lifestyle and diet.
THE PROCESS
Scientists have known at least since the middle of the nineteenth century that organisms throughout evolutionary history have been exposed to toxic substances in their environments and have developed ways to protect themselves from these toxic exposures. In the middle of the twentieth century, the question being asked—and the big push in laboratories everywhere—was about the process itself. Exactly what was it that protected organisms like us against toxic exposure? In 1955, Dr. Bernard Brodie, the founder and head of the Laboratory of Chemical Pharmacology at the National Institutes of Health, together with two of his students, Julius Axelrod and Jim Gillette, became famous for discovering an enzyme system that could detoxify foreign chemicals—that is, render them nontoxic and therefore harmless and ready to be excreted from the body altogether. Really, it was an enzyme supersystem, composed of more than fifty different kinds of enzymes, each with its own gene. In time, it was given a name—the cytochrome P450 system, CYP450 for short. Two scientists working at the McArdle Laboratory at the University of Wisconsin, Jim and Betty Miller, made the further discovery that CYP450 was principally located in the liver.
Then came the discovery that CYP450 was also involved not just in detoxifying toxins but in metabolizing substances native to all living cells. This meant that the supersystem did double duty: It protected us against foreign xenobiotics from the outside world and from toxic bacteria produced within our intestinal tracts, and it decontaminated the metabolic by-products in cells and got them ready for elimination from the body.
The problem is that this sets up a competition for the CYP450 enzymes. What are they going to do—transform particular products associated with normal metabolism or detoxify specific toxins? Both tasks are profoundly important and complex. Trying to do both at once can make an enzyme system—even an enzyme supersystem—end up cheating one or the other, if not both.
The analogy I use when I talk about this to my students is to ask them to think of the CYP450 enzyme supersystem as a room you’re dying to get into. A number of different doors offer entry into the room, and each door is another CYP450 enzyme, but you can enter the room through only one of the doors. Some of these enzyme-doors are big, like sliding-door entryways to major buildings, while others are narrow openings you have to squeeze into, like the folding doors to phone booths you see in old movies. The differences are of course due to each individual’s genetic uniqueness.
So let’s suppose that a bunch of substances crowd up trying to get through one of the narrow doors inside you, and they’re forced to enter one at a time. Some of those substances will no doubt be friendly substances—hormones just doing their job, for example. But some will also be toxins. The result will be a scramble at the entrance, with hostile toxins and benign friendlies vying with one another to get into the room through that single door, competing against one another to get some of that particular CYP450 enzyme. The result will be a buildup of both toxins and nontoxins, with only a small amount of either able to get through the door to be processed by the body and, in the case of the toxins, rendered harmless and flushed away.
Why is buildup bad? As with many things in life, while a small amount of toxins may not do any serious damage, a crowd of them can do a lot of damage indeed. Have you ever found yourself undone by a spacey feeling? You get the jitters or a headache, start sweating, or feel heart palpitations. These are likely to be early signs of toxicity that may come from an overload of the CYP450 detoxification system. That doesn’t mean you’re suffering serious poisoning, but rather that there is an imbalance in a component of your detoxification process. For the most part, the adage that “dilution is the solution to pollution” will restore the balance; drink a lot of water, and maybe add some soluble fiber to help flush the toxins out of your body as fast as possible. But such symptoms of toxicity just might signal a serious imbalance that needs to be taken very seriously indeed.
As for the friendly substances racing around in our bodies, while they are certainly essential for sustaining life, they too can become toxic if their level rises too high or drops too low. In other words, Mae West was wrong, at least about the benign substances in our bodies: Too much of a good thing turns out not to be wonderful, and the same is true for too little of a good thing.
Fortunately, the body has this process, detoxification, for keeping these substances—toxins and the useful substances that can become toxic—at appropriate levels, thereby controlling the chemical balance within the organism that is us. Keep in mind that the body is a seething mass of chemical reactions going on all the time. Catalyzed by enzymes, big molecules are being broken down by other molecules into smaller molecules, and components of cells are being constantly constructed and transformed. Anything that throws a monkey wrench into that process, altering the structure of a molecule or changing the amount of a certain substance, might compromise the body’s ability to detoxify what needs to be detoxified and can throw the whole organism off balance. Needless to say, such an alteration is to be avoided.
There are three main culprits throwing monkey wrenches into our detoxification process—medications, substances let loose into our natural environment, and substances within us. The alterations these three culprits can effect can indeed throw the process off balance and thereby adversely affect our health.
USEFUL CANARIES AND SCARY REACTIONS
To understand why the drugs we take for our health can harm us, we need to remind ourselves of the genetic uniqueness with which each of us comes into the world. Where the detoxification process is concerned, the genetic differences affecting CYP450 enzymes mean that each person detoxifies specific substances in specifically individual ways. Some people show a particular sensitivity to specific toxins; such people can be very useful in alerting the rest of us to possible risk from those toxins, serving the role of the canary in the mine shaft.
As recently as the early twentieth century, no coal miner would head down into the pit unless a canary was brought along. Sensitive to gases like carbon monoxide, the canary served as an early-warning system. If it stopped tweeting and grew ill, that meant that gas was present and it was time to get out of the mine—before the gas sickened or killed the humans working there. People who develop symptoms of toxicity long before the rest of us similarly serve as sentinels of danger, alerting us to the risk of exposure to specific xenobiotics.
Let’s go back to Alan and Sue and ask again how it is that Sue can drink eight cups of coffee a day and remain cool, calm, and collected while Alan is aflutter on one cup and would be jumping out of his skin on two. There’s a specific CYP450 that detoxifies caffeine preferentially; it’s the enzyme that “claims” caffeine. Like all enzymes in the body, its structure has been determined by the message coded for it that was locked into the genome at conception—your genome, my genome, the genomes of Alan and Sue.
Remember SNPs—single nucleotide polymorphisms—from Chapter 2? They’re the three million–plus infinitesimal variants that can occur in a single letter in the many-lettered genetic code of the DNA alphabet that makes up the gene. The SNP alteration slightly changes the meaning of the sentence that is the information of that gene, and while most SNPs do not radically affect the function of the body, the effect on the function of an enzyme can be significant—depending upon which letter in the alphabet coding for a specific enzyme gets changed. If you change the third letter in the word “deed” from “e” to “a,” for example, that’s a significant effect. “Deed” and “dead” are very different from each other.
It’s pretty clear that a particular SNP within the CYP450 family of caffeine enzymes in Sue’s genome is what lets her sail through the day unperturbed by an amount of the stuff that would leave the great bulk of the population pretty well jazzed. Another single SNP in the CYP450 caffeine family in Alan’s genome has him shaking like a leaf on what to Sue would seem a thimbleful of coffee. This makes Alan the canary in the mine for exposure to caffeine; his reaction—that is, the way his CYP450 detoxifies caffeine—alerts us all, except Sue of course, to the potential danger of exposure to this substance.
Can the differences really be that profound—that is, Alan shaking like a leaf on what to Sue would be a thimbleful? Emphatically yes. We know now that the genetic difference in drug detoxification between one person and another can be as much as a thousandfold. That is, the amount of a foreign substance that one individual’s physiology could detoxify might need to be a thousand times lower to prevent a toxic reaction in another individual.
Such profound differences have also given rise to the new scientific discipline of pharmacogenomics—the study of how people metabolize certain drugs and the recognition that no one drug fits all. Suppose you’re taking two different medications at the same time. We know that both will be detoxified by CYP450, but suppose that both require the same particular CYP450 enzyme for detox. Depending on the uniqueness of your particular SNPs for that CYP450 enzyme, your system could end up with that scramble at the door—that is, the two medications vying for the same CYP450. That might well overload the system and produce an adverse drug reaction—and a spacey feeling and jitters may be the least of it.
Adverse drug reactions have become an increasingly common and increasingly scary health-care phenomenon. It’s scary enough to contemplate the estimated 6.7 percent of hospitalized patients who suffer a serious adverse drug reaction to medications that are correctly administered by trained medical professions. It is downright frightening to realize that the most common adverse drug reactions in fact occur from the use of over-the-counter nonsteroidal anti-inflammatories (NSAIDs) or analgesics—especially acetaminophen—used by an estimated 36 million Americans every day without benefit of a doctor’s care.* The fact is that an individual’s unique genetic makeup is so powerful in shaping his or her detoxification process that you really have no idea what these “simple” over-the-counter drugs may be doing to you.
HOW DETOX WORKS
Why do we need a complicated physiological process to detoxify foreign, hostile substances? Can’t our bodies just excrete them directly through the digestive process of elimination via our urine and stool? Can’t we just breathe them out or sweat them out?
No. The reason—and therefore the problem—is that many of the most toxic substances behave like fats. Because our blood is principally water and because fats don’t dissolve in water, these fatlike toxins tend to stick in the body’s fatty regions instead of getting washed out and flushed away. They therefore have to be converted into substances that will dissolve in the blood so they can be transported into the urine and stool and get out of the body. The conversion is a chemical modification that makes the fatlike toxins look less like fats and more like water. That is precisely the first step of the detox process; it renders fatlike toxins into soluble nontoxins, and that is the job done by the CYP450 superfamily of detoxification enzymes. The result of it is a product called an intermediate, which, as its name suggests, is a substance created by one chemical modification and about to be used in another.
That “other” is the second step needed to complete the detox process. This second step is the job of another family of enzymes, also principally found in the liver, called conjugases. If you remember your Latin and the verb coniugo, to yoke together, you’ll know this is all about joining things. The conjugase enzymes take the intermediate from step one, the now-nontoxic substance, and add a chemical tail to it. There’s a huge variety of tails that can be added, but the conjugases will pick the one that is right for the specific intermediate, and the result will be a substance that is able to be transported into the blood and from there into the urine and stool more effectively.
This may seem like a lot more detail than you think you need to know, but here’s the punch line: The conjugation reactions depend upon the availability of substances provided through your diet. In other words, specific foods and their nutrients determine or certainly influence the effectiveness of your detoxification process. Compromise the detox process, and a toxic load of substances builds up in the body and poisons your metabolism. Have you ever had a hangover from too much alcohol? It was a result of overloading your detoxification process. You might have been able to stave off the morning-after hangover if you had eaten well the night before and drunk plenty of water along with—or, of course, instead of—the excessive alcohol. You might also have been able to prevent the morning-after effects if you had preceded your consumption of alcohol with the consumption of nutrients known to support alcohol detoxification—sesamin from sesame, magnesium, vitamin B1, vitamin C, coenzyme Q10, and N-aceytlcysteine (NAC). But you didn’t take either of those preventive measures, and your overburdened detox process is letting you know it with a headache, nausea, thirst, and a disinclination to look at sunlight.
If you are one of those people with a genetic intolerance of alcohol—that is, your genes don’t control the metabolism of alcohol effectively—and if you then consume foods or medications competing for the same CYP450 enzymes as alcohol, drinking could cause you real trouble. I don’t mean just a searing headache the next morning; I mean serious health problems. The double whammy of genes and what you ingest can put a real strain on your detox process, with really unfortunate results.
Go back to those adverse drug reactions from common, over-the-counter analgesics like acetaminophen—called paracetamol in much of the world. In the United States, acetaminophen is the source of the most common drug-related toxicity and of more ER visits due to poisoning than any other cause. The toxicity can be especially harsh in people who are taking the drug routinely and in recommended dosages—but while consuming alcohol or eating a poor-quality diet. Here’s why.
Step two of detoxifying acetaminophen conjugates the intermediate that results from step one, combining it with a substance called glutathione. You will hear a lot more about glutathione in Chapter 9, but what is important here is that both alcohol and a poor-quality diet deplete the amount of glutathione available in the liver. If you’re missing the key ingredient for step two of your detox process and your liver is exposed to a powerful toxin derived from acetaminophen, the detoxification of this powerful toxin is going to be inadequate at best, ineffective at worst. And that’s what seems to have happened in the case of many of these people heading to the ER with acetaminophen/paracetamol “poisoning”; the people suffering the reactions were the canaries in the mine for this kind of toxic exposure. Their alcohol intake and/or the foods they typically ingested in their poor-quality diet depleted their liver’s supply of glutathione and weakened that organ’s ability to detox what they assumed was a simple over-the-counter analgesic.
What do I mean by “poor-quality diet”? In the case of glutathione, important nutrients for its manufacture in the body include the sulfur amino acid cysteine, the amino acid glycine, the trace minerals iron and selenium, vitamin C, and the family of B vitamins. As we’ll see, you can get all of those nutrients in foods like garlic, onions, eggs, milk protein, and fish or in supplements.
Figure 3 illustrates all of this in some detail, showing how nutrients influence the process.
However you get or fail to get these nutrients, their effect represents an important example of how what we ingest can affect this core physiological process. But it still doesn’t adequately explain how and why toxicity is such a common cause of chronic illness. To understand that, we need to go outside.
WHAT RACHEL CARSON TAUGHT ME
Every now and again, someone writes a book that changes the way we think. It reframes the narrative we thought we knew so that we can never again see the world or ourselves in quite the same way. Its impact—culturally, socially, personally—can be enormous. Such a book for me was Silent Spring by Rachel Carson, published in 1962 and never out of print. It opened for me, as for millions of readers, a window of understanding into the potentially adverse health effects that low levels of exposure to persistent pesticides—pesticides that don’t break down easily into harmless compounds—could have on living organisms.
Carson had earned a graduate degree in zoology and genetics from Johns Hopkins University and in 1937 was working at the Bureau of Fisheries when she concluded that something in the environment was adversely affecting the viability of certain species of fish. Spurred by these observations, she went on for the next twenty-five years to delve deeply into the relationship between pesticide use and living species.
The same year Silent Spring was published, its author came to San Diego, California, to deliver a lecture at the local high school on the loss of seabird species due to pesticide accumulation in the birds’ fat tissue. I was a senior at that high school, and the lecture changed the course of my life. I decided to study chemistry and environmental sciences and went on to teach both and to make the connection between a healthy population and a healthy environment my lifework. I have always been grateful to Rachel Carson for that.
Carson’s work inspired many people and kicked off research all over the world into the kinds of things we do to our natural environment that may prove toxic to living organisms. At first, all we knew was that there was some sort of connection between very low levels of toxic substances—levels far below what traditional toxicologists would define as toxic—and adverse health effects in animals. The first signs of these adverse effects were subtle. They often manifested themselves as changes in an animal’s behavior or through an animal showing increased susceptibility to certain diseases. A number of researchers noted that these were the kinds of changes that hinted at alterations in the nervous and immune system functions of the animals.
By the 1980s, a biochemist at the University of Birmingham in England, Dr. Rosemary Waring, researching the relationship between xenobiotic exposure and neurological diseases, had found that animals exposed to low levels of pesticides and other toxic chemicals showed increased incidence of nervous system diseases. Waring later teamed with Dr. Glyn Steventon in the neurology department at the Queen Elizabeth Hospital, also in Birmingham, where for decades the two focused on the effect of long-term exposure to low levels of toxic substances, which can have serious negative influences on human health, often leading to such conditions as Parkinson’s and Alzheimer’s diseases. Their work demonstrated also that the influence is far greater in those with defective detoxification processes.
The story took another interesting turn in the late 1970s back here in the United States: a group of young men in the Bay Area of northern California presented to their doctors with Parkinson’s-like symptoms: tremor, gait disturbance, and postural changes. Parkinson’s disease is extremely unusual in younger adults, so this was considered atypical enough to prompt some detailed medical detective work.
One early finding was that the men were all marijuana users. This was at a time when the U.S. government was working with the Mexican government to reduce marijuana trafficking; one of the strategies in their joint effort was to get rid of the stuff at the source by spraying Mexican marijuana fields with the defoliant paraquat. Paraquat, it was learned, degrades under heat—as when a marijuana cigarette is lighted—and is transformed into a powerful neurotoxin called MPTP. Could the exposure to even a low level of MPTP in tainted marijuana have contributed to the Parkinson’s-like symptoms? Such a conclusion is in keeping with more recent research showing that such recreational drugs as Ecstasy and even cocaine can contribute to the neurological injuries that lead to Parkinson’s and Alzheimer’s diseases and possibly even to amyotrophic lateral sclerosis, ALS—Lou Gehrig’s disease.
Waring noted the same effect in paint and dye workers, printers, plastics workers, even people working in leather production. Although the level of chemicals they inhaled on the job was below what was traditionally considered toxic, they evidenced a small statistical increase in Parkinson’s disease. The level of their exposure, in other words, although low, was enough at least to influence individuals with susceptibility. They were canaries in the mine for these chemicals, as Waring confirmed in evaluating their CYP450 and conjugase activities, which showed one or more detox process inefficiencies.
Some argue that these examples are outliers; they happened only because there was a large exposure to the potential toxin. Yet today, in the era of pharmacogenomics, the truly pertinent question is this: Just how much exposure does it take to present a health risk to a particular individual? In essence, how much exposure constitutes toxicity? That’s a difficult question, inviting a far subtler answer than the standard toxicologist’s definition of “toxic.” For who can say how much exposure in any single individual is enough to influence mental state, energy levels, mood, and immune defense? How much is enough to increase the incidence of a disease that takes decades to become serious enough for a diagnosis—a disease like cancer, dementia, heart disease, diabetes, or arthritis? Trying to trace such conditions back to an earlier exposure to low levels of toxins is a little like watching shadow puppets. The exposure may set off movement toward a serious disease, but the effects are not obvious; they take place at the gene and cellular level, unseen and undetected, well before the development of an overt disease.
Yet the twenty-first century is seeing the emergence of just such a scientific discipline—molecular toxicology, the science that Rachel Carson brought to our attention. Molecular toxicology recognizes that we need to look for different types of toxicity when we are talking about low levels of exposure over the long term. Remember the old saw about the guy looking for his lost keys on the sidewalk under a bright streetlamp? A passerby offers to help and is instructed to look across the street, where it is dark. “If you lost the keys over there,” says the passerby, “why are you looking for them over here?”
“Because,” answers the guy who lost the keys, “this is the only place where I can see.”
If your only definition of a toxic effect is a serious disease that immediately follows exposure to a toxin, then you will never find the keys to understanding the influence of chronic, long-term exposure. You have to look in the shadows—for the molecular toxicity inside the function of cells—to find the keys to the toxicities that lead to chronic illnesses.
THE BPA STORY
It was in the shadows that scientists stumbled upon the story of bisphenol A, a compound common in the environment because it has been used for decades to keep plastics flexible. In fact, it’s called a “plasticizer,” and you’ll find it in water bottles, sports equipment, DVDs, and a range of other commercial products. BPA, as it’s known, is a persistent chemical in the environment: it does not break down; rather, it accumulates. Moreover, it concentrates in fats.
BPA was first used in 1957, but even by the 1970s and 1980s, the levels of BPA in the environment remained undetectable by most of the analytical instruments available to measure its presence. The sarcastic maxim, “If you can’t measure it, assume it doesn’t exist,” seemed to be in the ascendant. By the early twenty-first century, however, thanks to significant advances in the technologies for measuring very low levels of chemicals in the environment, BPA was shown to be associated with adverse health effects in certain organisms and in certain environments. Studies were then undertaken to measure the levels of BPA in the urine and fat tissue of humans, and the results showed the presence of levels that had been harmful in other species. The next step was to correlate data on the levels of BPA in children and adults with data on the incidence of certain chronic diseases. The results were shocking.
In 2008, a paper in the prestigious Journal of the American Medical Association (JAMA) reported on findings from the Peninsula Medical School in Exeter, England, that elevated urinary levels of BPA were associated with the incidence of diabetes in adults. Four years later, a subsequent research paper from Dr. David Melzer’s group at the Peninsula College of Medicine and Dentistry, this paper in the journal Circulation, reported that elevated urinary levels of BPA in apparently healthy men and women were associated with increased incidence of heart disease. If that weren’t enough, Dr. Leonardo Trasande’s group at the New York School of Medicine reported that same year in JAMA that elevated urinary levels of BPA were strongly associated with obesity in children and adolescents.
Diabetes, heart disease, childhood obesity. Yet what was truly striking about all this varied research was that the level of urinary BPA associated with these health risks was extraordinarily low—so low that it wouldn’t even have shown up in the measurements that analysis was capable of taking twenty years previously. In other words, what had not even registered on the radar for nearly five decades of BPA’s existence was now demonstrably a potential health threat to humans of all ages.
Why is BPA a threat? It belongs to a large family of chemicals described as endocrine disruptors. The endocrine system is the body’s hormonal messaging system, so if it gets disrupted—if messages are altered—the impact on our health can be significant. BPA binds to receptors on cells that the body’s natural hormones use to regulate physiological function. In doing so, BPA displaces the natural hormones—basically, knocks them off the receptors and takes their place—and thereby sends different messages to the cells. Moreover, because many of these endocrine-disrupting chemicals are very active, it takes only a very small exposure to create significant changes in health.
This is toxicology on a very basic molecular level, and it is changing the way we think about what is toxic and at what level. You will not be surprised to learn that not everybody is wild about pursuing studies that go this deep. Powerful lobbying forces—namely, the American Chemistry Council, the industry association for chemical manufacturers—worked very hard for many years against a ban on the use of BPA in baby bottles and sippy cups. The ACC relented only when it decided the ban would actually boost consumer confidence in other chemicals. It’s a reminder that old perceptions die hard—especially when money is at stake.*
THE “ENEMIES” WITHIN
To the toxins that come from outside our body—the exotoxins that enter us through medications or from substances in the environment—must now be added the endotoxins we produce inside our bodies that disturb the activity of our intestinal bacteria. We know that our enteric microflora perform essential functions that benefit the human organism—functions having to do with energy production, strengthening our immune system, preventing the growth of harmful bacteria, regulating how we store fats, even producing vitamins. So anything we produce that meddles with those functions is going to be potentially harmful.
In a collaborative effort, researchers from my own Functional Medicine Clinical Research Center joined with a remarkable group of investigators at the Catholic University of Leuven in Belgium headed by Professor Nathalie Delzenne and Dr. Patrice Cani to look more closely at this issue. The project explored how alteration of the intestinal bacteria through lifestyle, diet, medications, alcohol, and stress could affect levels of endotoxins in the blood. The project found that since these endotoxins influence the same detoxification processes as those for the detoxification of exotoxins, the result of increased levels of endotoxins leads to what the group termed a total-load effect. In other words, the researchers concluded that it doesn’t matter where the toxins come from. What matters is how big a burden they place on specific participant components in the detoxification process. In a system that is overloaded, toxic substances can slip through the detoxification process, evading certain detox steps and thus adding to the adverse impact on health.
For example, a person with an imbalance in his or her assimilation-elimination process is likely to be more susceptible to the adverse influence of exposure to foreign chemicals and drugs. Yes, on one level, that’s simply because the intestinal tract is connected to the liver and what happens in the seat of the assimilation-elimination process, the gut, naturally touches what happens in the seat of the detoxification process, the liver. It is also because the intestinal tract has its own very active detoxification system, located right in the cells of the intestinal lining. That location means that some ingested xenobiotics and potentially toxic by-products derived from intestinal bacteria may start to be detoxified even before they get into the blood.
What do these connections between the assimilation-elimination process and the detoxification process tell us about curing chronic illnesses? They tell us that if we combine the Four R program found in Chapter 4 for intestinal restoration—that is, for managing problems associated with an imbalance in the intestinal microflora—with a detoxification program to manage an imbalance in toxic exposure, we can deal with two major contributors to chronic illness.
DEFINING A DETOX PROGRAM
In the early 1980s, I met a remarkable physician, William Rea, who had been a successful cardiovascular surgeon in Dallas until he became impaired. The impairment was clearly neurological; Dr. Rea’s symptoms manifested themselves as a disturbance in his balance and walking ability. He was one of those canaries in the mine shaft, although he didn’t yet know it. But he took his impairment very seriously and went hunting for an explanation.
His detective work led him to the hypothesis that his impairment came from a toxic reaction to substances used in the operating room, where he spent most of his working day. In other words, environmental exposures were the cause of his problem. His solution was to make his personal environment as nontoxic as possible—and his symptoms improved dramatically. The experience prompted Rea to establish in 1974 a pioneering environmental medicine clinic to assist patients who suffer from environmental illness. Over the years, he has treated more than thirty thousand patients with varying degrees of such illnesses and has tested and perfected various ways of improving the detoxification process. No wonder in 1988 Dr. Rea was appointed as the first-ever chairman of environmental medicine at the Robens Centre for Public and Environmental Health at the University of Surrey in England.
The Rea program for detoxification follows the principle articulated by Dr. Sidney Baker and reported in Chapter 2: Take away the things that are bad, and replace them with the needed things that are good. This is a wonderful objective, but the devil is in the details. How can we apply it to the individual in need of detox?
Because Dr. Rea often sees the most seriously ill patients, his intervention programs are extremely aggressive; they go beyond what would be required in the case of most chronic illnesses. Patients are tasked rigorously to remove from both home and workplace any and all synthetic materials that might release gases or vapors or contribute residues; that includes all carpeting, paints, and flooring materials. He recommends air and water purification and clothing made only of natural fibers and containing no synthetic materials. He prescribes organic foods only but excludes such common allergy-producing foods as dairy and grain products. No perfumes, colognes, or fragrances. No cell phones; Dr. Rea believes they may cause electromagnetic pollution. In essence, he asks patients to undergo a complete change in lifestyle and environment. If it seems drastic, its results have been dramatic.
Fortunately, for most people with environmentally based chronic illness, the need for change is not nearly so radical. I credit Dr. Jean Monro, a founder of London’s Breakspear Hospital, which treats patients ill from environmental exposures, with pointing the way to a kinder, gentler, more temperate detoxification process that can manage mild toxicity problems without requiring a complete change of lifestyle and diet. Dr. Monro is a most remarkable medical doctor; raised in India and medically trained in England, she has a particularly global view of disease and the role that lifestyle and environment play in it.*
I remember meeting one of Dr. Monro’s patients, Mia, during a visit to her office several years ago. An advertising executive in her midforties, Mia was a very engaging woman in every way. About a week after returning from a holiday in Spain, she noticed that it was becoming really difficult for her to get out of bed in the morning. Moreover, once she managed to get up and dressed, she unaccountably felt “weak and sore all over,” as she put it, and she even thought she experienced a difference in her breathing. When she noticed red patches on her skin, she made an appointment with her doctor.
At first, he thought she might have a form of autoimmune disease like systemic lupus erythematosus—SLE—which is not uncommon in women in their forties and which presents with symptoms like those Mia described. Puzzled, he recommended she see a rheumatologist, and she made an appointment for the following week.
In the meantime, however, a friend at work suggested she see Dr. Monro first. She did so and was curious that Dr. Monro asked about her trip to Spain, questioning her as to whether she had been exposed there to anything unusual. Mia couldn’t recall anything that fitted the definition of “unusual” until Dr. Munro asked her whether she had eaten any fried food.
“Oh!” said Mia. “Every day.” She had loved the fried seafood at a particular restaurant and had gone there for a meal at least once a day for the entire two weeks of her vacation.
The answer set off bells in Dr. Monro’s brain. She knew about the Spanish cooking oil that had been contaminated by an industrial toxin and had been responsible for nearly six hundred deaths in the early 1980s. She put Mia on a strict detoxification diet plan, and within three months, Mia had regained her strength and function—without medication and without hospitalization. She has remained symptom-free ever since.
It sounds simple, yet this outcome and others like it are dramatic evidence of how diet can influence the natural physiological process of detoxification. The evidence was impetus enough for me to want to understand how to develop and apply a diet that would support the body’s own detoxification.
One of my first stops along the path to understanding was a visit in 1992 with Dr. Elizabeth Jeffery, a professor at the University of Illinois in the Division of Nutritional Sciences. She and her students have been involved in pioneering work that demonstrates how cruciferous vegetables have a unique ability to promote detoxification. Specifically, these “cross-bearing” plants of the cabbage family—like broccoli, cauliflower, and brussels sprouts (as well as cabbage, of course)—contain specific nutrients called glucosinolates that improve the detoxification function. How? Many of the genes that control the detoxification process are inducible, which means that their function can be turned on and off as a consequence of exposure to specific substances. The glucosinolates in the cruciferous vegetable family are substances that specifically turn on many of the genes that regulate detox. The more of them you consume, therefore, either by eating your vegetables or by taking a food supplement containing the concentrated glucosinolates—such supplements will have names like indole-3 carbinol and sulforaphane—the more powerfully will you activate your detoxification process.
A Rockefeller University professor of biochemistry, Dr. H. Leon Bradlow, has discovered that the same glucosinolates in crucifers that help to detoxify foreign substances also help women safely metabolize and eliminate the estrogen their bodies produce. The basis for that conclusion is Bradlow’s finding that the detoxification of estrogen hormones in the body is done by the same CYP450 and conjugase enzymes that are stirred to activity by the glucosinolates in cruciferous vegetables. If you’re a woman who may be producing too much estrogen and who, as a consequence, is at risk from your own estrogen for breast cancer, you should know that you can boost your estrogen management with a diet rich in cruciferous vegetables.
Further understanding has come from the work during the 1990s of Dr. Paul Talalay, a physician and the Abel Distinguished Professor of Pharmacology at the Johns Hopkins School of Medicine, who found that the glucosinolate-derived sulforaphane from broccoli and brussels sprouts serves as a protective agent against cancer. How so? Talalay attributes the protective power of sulforaphane to its ability to improve the detoxification of potential cancer-causing substances. The improvement is in the way the sulforaphane talks to genes. Different substances give the genome different messages that turn on the detoxification processes in different and very selective ways. Some food substances affect the CYP450 enzymes; others influence specific conjugation steps. Sulforaphane, says Dr. Talalay, does both; it activates a combination of specific CYP450s and conjugase enzymes that work together to detoxify potential carcinogens. We call phytonutrients like sulforaphane “bifunctional detoxifiers” because they communicate to genes that control both CYP450 and conjugase activities.
Could any of these diet or lifestyle changes work to reduce the amount of BPA that might be stored in our bodies? Over the years, we have actually learned a lot about the specifics of BPA detoxification, and the simple answer to the question is that increasing the dietary intake of soy, kale, cranberry, and green tea as well as of the spices turmeric and rosemary can help eliminate BPA from our bodies. All these foods are known to contain specific substances that increase a particular component of the detoxification process called glucuronidation. In lieu of a detailed explanation, suffice it to say that glucuronidation is a process that makes it easier for intermediates of the metabolic process that relate to BPA detoxification to be transported around the body—and out of it. And that, in turn, is how to eliminate BPA.
Indeed, the scientific explanation of how very specific elements of our diet can influence the detoxification process and help us eliminate toxins is writing a whole new chapter about how what we eat can help us manage chronic illness.
A DETOX DIET?
So if we were looking for the optimal diet plan to support the detoxification process, what would it be? All the signs point to a high intake of vegetables, fruits, beans, and whole grains; moderate consumption of meat, eggs, fish, and dairy products; and low intake of processed foods, fats, and sugars. Such a way of eating is sometimes called an alkaline ash diet. It decreases the production of acid metabolic by-products that may impede the kidneys in their job of eliminating detoxified by-products. Another trick for increasing the elimination of toxins is to consume 1,000 milligrams of potassium citrate in water after each meal; potassium citrate is an alkaline salt, so it too improves the body’s acid-alkaline balance.
Here’s a list of some other specific foods and beverages that contain phytochemicals known to support the genetic expression that regulates detoxification.
• Green tea, which contains catechins
• Turmeric, which contains curcumin
• Soy, which contains genistein
• Cruciferous vegetables, which contain glucosinolates
• Red grapes and Spanish peanuts, which contain resveratrol (in the skin of the peanuts)
• Watercress and pomegranate, which contain ellagic acid
• Hops, which contain humulones
These foods offer an added benefit: They have a positive influence on the expression of genes that regulate those detoxification processes associated with toxic mineral accumulation. Toxic mineral accumulation is definitely something you do not want.
LEAD, MERCURY, CADMIUM
In 1980, I met a remarkable medical researcher, Dr. Herbert Needleman, at a conference at Harvard University Medical School. Needleman had just published in the New England Journal of Medicine an important and highly controversial paper on his work with children in the Boston area; the title of the paper was “Deficits in Psychological and Classroom Performance of Children with Elevated Dentine Lead Levels.”
Needleman’s study had measured the ability of elementary school children to stay on task—basically, to concentrate. He had then correlated the data with the results of a standard IQ test and with measurements of the level of lead in the children’s baby teeth. The results showed a strong correlation between elevated lead levels in the deciduous teeth—baby teeth—and both a lower IQ and lower ability to stay on task. This effect persisted across all socioeconomic backgrounds.
To many people, this conclusion was simply shocking. At the time, lead was everywhere—in gasoline, in the paint that covered the walls of most homes, in batteries, in plumbing, in dozens of common household items. Roadside dust was found to have elevated lead levels, and so was the dirt in school playgrounds.
In a conversation I had with Dr. Needleman twenty-five years after his paper was published, he spoke honestly and feelingly of the extent to which he had underestimated the intensity of the emotional reaction the publication unleashed. He found himself under attack, to put it mildly, by representatives of the industries that use lead in their products. The attacks were not pleasant. The integrity of his research was questioned and his professional bona fides derided. Over time, of course, he was proved right, as the story of what exposure to even low levels of lead can do to brain function in children was confirmed time and again. Today it is recognized that low levels of exposure to mercury and cadmium as well as to lead—from environmental and food sources—can be toxic to the body’s nervous, cardiovascular, and immune systems. And they are in us; all three are common environmental contaminants that become more and more concentrated in organisms the higher up the food chain you go.
Against these contaminants, diet is again a factor. Toxic minerals are detoxified not by the CYP450 and conjugase enzyme systems, but rather by a system comprising a family of proteins called metallothioneins. These proteins are genetically programmed to be manufactured within virtually all the cells in the body. Their role is to bind minerals very tightly and to conduct the exit of minerals from the body via elimination in the stool or urine. What stimulates the manufacture of the metallothioneins is pretty much the same set of dietary factors that increase the detoxification of the persistent chemicals that don’t break down easily but rather accumulate. We think this shared mode of stimulation is probably due to the fact that both these functions—the genes that control detoxification and those that control the manufacture of metallothionein—sit very close to one another in the genome. It seems likely they would share a mechanism that stimulates their detoxification processes.
What are the foods that put that shared mechanism in motion? Metallothioneins are very high in the sulfur-containing amino acid known as cysteine, which binds minerals very tightly. In fact, this particular kind of binding is called chelation, from a Greek word meaning “clawlike.” Metallothioneins containing cysteine almost literally claw lead, mercury, and cadmium out of the body. So proteins with sulfur-rich cysteine—like eggs—as well as sulfur-rich foods like onions, garlic, leeks, and asparagus will spur detoxification. So will foods rich in soluble fiber—like oats, barley, and soy. If you’re designing a diet to support detoxification of mineral toxins, these foods are key.
A DETOXIFICATION STORY WITH A HAPPY ENDING
Jennifer was a dental hygienist who suffered serious numbness and tingling in her hands and feet. Her own doctor had ruled out the common causes for her complaints and, unable to find a remedy for her, had referred her to our group to participate in one of our research studies. After similarly ruling out standard diagnoses in their evaluation, our physicians decided to examine the level of mercury in her blood. As a dental professional, could Jennifer have been exposed to enough mercury on the job to create chronic symptoms of toxicity?
Her blood indeed showed a level above the upper limit of acceptable, although not high enough to constitute mercury poisoning. The doctors prescribed a specific, dimercaptosuccinic acid (DMSA), to pull mercury out of her body and release it in the urine, then followed up with a urine test. It showed enough mercury being excreted that it was safe to assume deposits of the mineral were “hidden” in her body.
The doctors put Jennifer on a detoxification program that emphasized the foods high in sulfur including members of the allium family of garlic and onions, eggs, chicken and fish, along with foods that increase the gene expression of the metallothioneins such as grapes with their skins, green tea, zinc, the herb Andrographis paniculata, and the phytonutrients curcumin from turmeric and isohumulones from hops, as well as oral capsules of charcoal, which is known to improve the elimination of toxic minerals. They also recommended that she engage in rigorous office hygiene to reduce her exposure to mercury at work.
Progress was slow in the beginning, and there were times that Jennifer felt she would prefer to take a stronger medication approach to her problem. But since she could feel some improvement, she persisted.
First, her fingers, which had seemed to “go to sleep at night,” began to feel normal. Within a month, the tingling in her toes and on the soles of her feet had disappeared. Within six months, all of Jennifer’s symptoms were gone, and a follow-up blood test indicated that the level of mercury in her blood was now within a low normal range.
Yet there are still people who say there is no such thing as a detoxification diet, and that there is nothing to be done about the signs and symptoms of chronic toxicity. Yes, there are detoxification diets of questionable validity out in the marketplace, but the substance of the process of detoxification and the role of diet in that process are scientifically valid, as is the clinical experience of tens of thousands of patients like Jennifer.
Here’s the simple truth of it: an imbalance in the physiological process of detoxification can result in the canary-in-the-mine-shaft syndrome, making the individual susceptible to exotoxins and endotoxins that he or she would normally have been able to detoxify and eliminate before they could do harm. Of course, the process intersects with that of assimilation-elimination, which in turn intersects with the core process of defense.
CHAPTER 5 TAKEAWAY
1. Detoxification processes defend the body against exposure to toxins from both the environment and the process of metabolism.
2. Detoxification is genetically controlled and highly individual.
3. The level of toxicity is a result of the total load of exposures to environmental pollutants, dietary contaminants, toxic by-products produced by intestinal bacteria, and substances produced through metabolism.
4. The most common symptoms of toxicity are related to nervous and immune system dysfunction.
5. Children and pregnant women have been found to be particularly susceptible to toxic exposures.
6. Chronic exposure to lead, mercury, and cadmium in the environment has been identified as a significant contributor to toxic symptoms.
7. A program comprising specific steps to reduce exposure to toxins and the use of specific foods and nutrients to eliminate them can improve the detoxification function.