Chapter 2: Nutrigenomics and the Methylation Cycle

The Dawning of the Age of Personalized Medicine

Today we stand at the dawn of the age of personalized medicine. Integrative medical doctors herald its potential, drawn from traditional medical approaches—like Chinese and Ayurvedic medicine and homeopathy— that emphasize individuation of treatment. Conventional medicine, too, looks forward to breakthroughs in this new field, although it’s been predicted that it may take several decades before these new understandings can be applied. But, I ask, why wait? There is urgent need today! We have the technology and knowledge—now. We are able to look at crucial nutritional pathways and examine their underlying genetics—now. We can customize programs to meet individual unique needs and make a difference—now. That’s what this book is all about.

With the mapping of the genome, we now know that there are approximately 25,000 genes in the human organism, but thus far they have yet to be sufficiently well characterized. The result is that clinicians are able to apply their understanding of genetics to just a few factors applicable in day-to-day health care practice. With extensive expertise in biochemistry and molecular biology, I was a principal of a biotechnology company and pursued research in this arena for over fifteen years. I know that over time, as we map the genome, we will learn more about the properties and functions of each and every gene. We can look forward to the day when we are able to identify risk factors throughout the entire human genome in order to optimize health and prevent adverse health conditions. However, since that work is already underway, why not put into practice what we know now?

One reason that this form of health care is not yet considered standard is that it’s only a rare individual who can afford to undertake genetic testing for all the body’s 25,000 genes. And even for the few who are able to do that, the information they derive may not be very useful or applicable until the genes have been better characterized by scientists—in the far-flung research process now underway.

As a result, and in order to operate more cost effectively, some clinicians and labs have identified and offer testing services for a narrower range of genes. Through genetic testing of genes, we are able to identify the specific genetic mutations, also called “single nucleotide polymorphisms” (SNPs—pronounced snips) within each individual. People with specific health conditions or risk factors seek this information to more accurately target treatments and preventive strategies based on their test results. If you search the Internet, you will see that various labs offer genetic testing services, typically testing somewhere between 20 and 35 SNPs.

But the critical question in undertaking any such genetic test is: Which SNPs should the lab test? Testing approximately thirty or so can cost anywhere from $500 to $1500, a significant expense that most insurance doesn’t cover at this time. So, before undertaking any tests, it’s vital to assure that the lab will examine (and report consistent and accurate results for) the genes most essential to you or your child’s health condition. My work over the last several years has been to define what I believe to be the most effective range of genes to test, and to do the groundwork of characterizing those genes, which means identifying what they do and how their performance interacts with other genes to perform critical bodily biochemical functions.

As a result, in this book, as in my talks, DVDs, and chat-room comments, I share my hypotheses and new discoveries as this ongoing research evolves. When you are first introduced to this science, it can sound a little complicated—and it is a complex and wondrous science. However, over time you will become more familiar with it.

Why Get to Know Biochemistry and Molecular Biology?

Gaining some comfort level with molecular biology and biochemical pathways will help you:

  • Understand the causes of the symptoms experienced.
  • Monitor program responses and results.
  • Determine when to add or subtract supplements and when to test.
  • Understand the reasons for the specific nutritional supplements we use to bypass areas of genetic weakness.
  • Feel reassured about the scientific validity of the treatments recommended.

Most of all, becoming familiar with this science will empower practitioners, parents, and adults with health issues. For far too long, people have left their health nearly entirely in the hands of others. While it’s vital to rely on those with expertise, it’s also essential to be informed, aware, and motivated to take action oneself. Getting to know some of the underlying science is an opportunity to do that.

But do it at your own pace. In this and succeeding chapters, the most basic information is contained near the front of the chapter. The later, more detailed scientific material, toward the back of each chapter is there for your reference, and will become clearer with repeated readings (and experience of the program) over time. Although this is only a basic entrée into the underlying science, far more extensive information is available to you in my lectures, which are available on DVDs, and in my other books. This book could not contain it all and still be a handbook for practitioners and parents. Please know that I continue to add to our understanding and develop this foundational science through my replies to posts in the chat room on my website, www.holistichealth.com. By joining the chat, you can search for and find answers to the most common questions, receive support from other parents, ask your questions, and get answers. All the scientific articles that serve as the foundation of this approach are also found on this site. Once again, this book is primarily a handbook and is therefore not footnoted.

Neurological Inflammation

More than ten years ago, I began to research the genetics of neurological inflammation, the physiological precursor to a number of adult health ailments, such as chronic fatigue syndrome (CFS), Parkinson’s disease and MS. At that time, it was not my plan or design to work with children with autism, but as chance or destiny brought me the first children with whom I worked, I began to recognize that, just like these other neurological ailments, the condition we call autism arises from underlying neurological inflammation and therefore can benefit from approaches similar to those I offered to my adult clients.

One contributor to neurological inflammation is the overexcitation of neurons in the nervous system and brain, leading to misfiring, exhaustion, and death of these nerves. As I looked more deeply into the biochemical factors that mediate and/or contribute to neurological inflammation, both ground-breaking research and clinical results demonstrated that one particular biochemical pathway is key. As a result, I’ve concentrated my efforts on forging a more complete understanding and characterization of that pathway: the methylation cycle.

There are a vast number of different and distinct biochemical pathways in the body that interact to perform all the many complex functions that are going on all the time without our awareness. So what makes this particular pathway so unique? First of all, I know from analyzing thousands of tests that an extraordinarily high percentage of children with autism have one or more mutations in this pathway, compared to the rest of the population. Secondly, I believe that the proper functioning of this pathway is critical to overcoming any form of neurological inflammation. This does not mean that every individual with mutations in this pathway will develop autism; problems with the methylation pathway may be a necessary but not a sufficient condition for autism.

What I refer to throughout this book as the methylation cycle is actually a combination of four interrelated biochemical cycles, including:

  • The methionine cycle
  • The folate cycle
  • The BH4 (biopterin) cycle
  • The urea cycle

To my knowledge, no other clinician has traced the interactivity of these four cycles or emphasized their function for clinical practice as much as I have, although the folate and methionine cycles are widely regarded as interactive. To describe and evolve a program based on what I am calling the methylation cycle required combining divergent pieces of information not previously connected in order to recognize and find approaches to address the synergistic functioning of these four cycles. It’s by considering them all together as the “methylation cycle” that we create a solid foundation for addressing critical dysfunction.

The New Science of Nutrigenomics

Over time, I’ve evolved a holistic approach for bypassing genetic issues in the methylation pathway through the use of the budding science of “Nutrigenomics.” Nutrigenomics is a hot new area of research that you may have read about, based on the understanding that, while we cannot change our genes, we can change the way our genes act. For example, certain foods or supplements prompt our genes to act in healthy or unhealthy ways. Through the study of Nutrigenomics, scientists are learning what to eat (or to avoid) to promote healthy vs. unhealthy “genetic expression.” Using Nutrigenomics, labs compare the genomes of a large sample of individuals to determine which genetic “print-outs” represent “normal” vs. mutated variations.

Genetic expression = How our genes act

For example, a man—let’s call him Hal—may have a slight tendency to be irritable. Let’s say that is part of his disposition, his basic makeup. Nevertheless, overall he’s a solid, well-intentioned man—until a hot summer’s day at a family picnic, when he gets a bit too much sun. Next, Hal eats spicy chili and drinks a few martinis. Before you know it, his teenage son does something that annoys Hal, and his temper flares. Another person with less of a tendency to become inflamed and angry might react differently. But for Hal, staying out of the sun, perhaps drinking mint tea, and eating a salad would help manage his innate tendencies. In just the same way, by knowing more about our genetics we can help our genes to respond favorably, rather than flare and cause an undesirable reaction.
The goal of Nutrigenomics is to supply the body with the specific nutritional ingredients it needs for healthy functioning on a daily basis. Most of us have genetic mutations of some kind.

Nutrigenomics is genetically targeted supplementation.

These mutations impair our ability to perform all the biochemical actions necessary for ideal function. As a result, we may produce too much or too little of something, creating biochemical imbalances that lead to dysfunction and ultimately to health problems. Through supplying the missing nutritional ingredients that the body requires but cannot adequately produce itself due to genetic mutations, Nutrigenomics helps us to, in effect, “bypass” the genetically induced decrease in function, and restore proper functioning.

Genetic Testing

To determine which of our genes may have mutations, we must first undergo genetic testing. I don’t believe that it’s advisable—or indeed ethical—to perform genetic tests out of idle curiosity. Unless the clinician can offer an approach to address the genetic defects that testing may reveal, I don’t recommend it. That’s why I’m not in favor of random testing. As a result, my focus has been on the testing of genes and the Nutrigenomic support of genetic mutations in a pathway critical to health, the methylation pathway. By using nutritional supplements derived from natural substances to address gene defects, we can improve function and restore health.

A Tale of Two Mice

Folic acid is a crucial nutrient produced by—and contributing to—methylation. In a classic study, two groups of mice were given the same diet, except for the level of folate. The group that received higher folate levels produced more methyl groups—a carbon with three hydrogen atoms—which altered the expression of DNA, which in turn resulted in a visually noticeable difference between the two groups: The ones that produced more methyl groups had a different fur color, body weight, and size than the control group.

Folate is a very common ingredient in nutritional supplements. Yet scientists recognize that about 40% of Americans have an SNP (a mutation) that limits or eliminates their ability to process common folate. Most people with this mutation are unaware of it. To benefit from supplementation, then, these people require a special form of folate.

Folate is a part of the very specific pathway we look at, the methylation cycle, and that is why the testing we do focuses on certain key aspects of the body’s ability to use folate properly.

The bottom line is that through focused genetic testing and the application of Nutrigenomics, we can:

  1. Identify the presence of SNPs in key places in the methylation cycle.
  2. Use the right supplements to control how these genes act, in effect bypassing the genetic mutations to optimize methylation cycle function.
  3. Benefit from all of the necessary tasks performed by a functioning methylation cycle.
  4. Reduce (and repair the effects of) neurological inflammation to improve the biochemistry of the various bodily systems, supported by methylation.
  5. Over time correct imbalances, relieve symptoms, and optimize a person’s potential for good health

This series of steps is really the foundation of this program and has been used successfully to address the various conditions that arise from neurological inflammation, including autism, chronic fatigue and immune dysfunction syndrome (CFIDs,) and neurological ailments—but, as mentioned earlier, its application may not be limited to these areas. We’ll revisit this throughout this book. But for now, let’s look at what happens when the methylation cycle is impaired by a combination of genetic weakness and environmental impacts.

Why Do We Need Methylation?

Why have I singled out this particular pathway? What functions does it perform in the body? Why do we care about methylation at all?

Going forward in this chapter, I’ll explain the key functions of this pathway and describe why we need it for so many key bodily processes. In addition, I’ll briefly review some of the key functional areas that are impacted by inadequate methylation, as well as highlight a few of the issues that can manifest when the methylation cycle is not doing its job well.

Methyl Messengers

Methyl groups are the body’s messengers and movers and shakers. They join with other compounds to “jump-start” a reaction (such as turning a gene on or activating an enzyme). When the methyl group is “lost” or removed, the reaction stops (or a gene is turned off or the enzyme is deactivated), OR when a methyl group is lost a gene is turned on (for example, a gene related to cancer) when it is not ideal to have it turned on.

When the methylation pathway performs well, it produces various byproducts, including biochemicals needed to perform other tasks. For children with autism, as for adults with neurological and other conditions, the healthy byproducts of methylation do many essential things, which you will be introduced to in this chapter. On the other hand, when the methylation pathway is not well functioning, there are two principle results:

  1. A wide range of key bodily functions will not be performed effectively.
  2. The byproducts of this pathway can lead to inflammation, a precursor to various conditions ranging from autism to Alzheimer’s to cardiovascular disease.

Which Genes Should We Test?

If testing 30–35 genes is currently the most practical approach to genetic testing, then you want to test where it counts. You want to get all the crucial information, focusing on genes that govern a vital functional area, rather than using the scattershot approach common in certain genetic tests, which test a little of everything. To see why that’s important, imagine that you have Googled driving directions to a city you want to visit. You need a detailed map that shows every major turn onto the roads that lead to your destination. It wouldn’t do you much good to receive directions that omit key turnoffs, leave out main roads, and instead show you a few addresses in twenty other states. In effect, some genetic tests do just that. The test designers may be well-intentioned, but in my opinion, scattershot testing does not produce reliable “directions to the destination.”

Why? Because like people, genes do not function in isolation—they are interconnected. Imagine each biochemical pathway as a kind of assembly line in which a series of actions occur in sequence. When a given gene does its job well, it creates a biochemical that receives something produced by an upline biochemical and does something with it, and it then passes it along to a biochemical downline, almost like passing a baton in a relay race. Therefore it’s essential to study not just isolated genes, but biochemical function along specific pathways. To troubleshoot where the problems are, we need to know how well both the up–and downline genes and allied biochemistry function. That way we can make all the corrections necessary to recreate proper pathway functioning.

By characterizing the effects of genetic polymorphisms at key areas of the methylation pathways, it’s possible to create a personalized map of specific, individual imbalances that can impact your child’s or your own health. When we identify these precise areas of genetic fragility via Nutrigenomic testing, it is then possible to target appropriate nutritional supplementation to optimize the functioning of these crucial biochemical processes.

Why have I elected to focus on the methylation pathway? Because both the research literature, as well as my own clinical work, have revealed its centrality to a number of significant bodily processes.

Autism: A Multifactorial Condition

As I mentioned in chapter 1, it’s important to recognize that autism is a multifactorial condition, with genetic, infectious, and environmental contributors. What makes the methylation cycle so unique and so critical for health is that mutations in this pathway can have an impact on all of these factors. This concept is so important that I will repeat it, just to be sure you have gotten the message:

Autism is a multifactorial condition, with genetic, infectious, and environmental contributors.

What makes the methylation cycle so unique and so critical for health is that mutations in this pathway can have an impact on all of these factors. Picture each mutation as an accident causing a traffic tie-up. One accident will slow down the flow of vehicles on the highway. A second or third will snarl things even more. Through targeted supplementation, we are in effect creating a way for a vehicle to bypass the sites where the accidents have occurred, take a detour, and move further toward its destination. In the case of the methylation highway, these bypasses permit us to move beyond the blockades caused by mutations to produce and deliver the methyl groups that are key to a wide range of bodily functions.

Each methyl group consists of a carbon atom bonded to three hydrogen atoms, CH3. But since a carbon atom can bond with four other atoms, each methyl group has one more available bond, which constantly attaches to and detaches from numerous other molecules in the process known as methylation.

It is their ability to connect and create a new process that makes methyl groups so important.

Methylation Is the Message

Methylation is involved in almost every reaction in your body and occurs billions of times every second in your cells. To give just a few examples—and you will encounter many more throughout this chapter—without proper methylation, there is increased vulnerability to viruses, impaired attention span, and less efficient nerve transmission. We can get a basic idea of the impact of methylation on the nervous system by looking at the effects of coffee and the drug Ritalin. Coffee has a large number of methyl groups, which is why it causes such a sudden improvement in focus. And because Ritalin is a methyl donor, children on Ritalin may also experience improved focus.
Methylation is central to such critical reactions in the body as:

Repairing and building RNA and DNA
Immune function (how your body responds to and fights infection)
Digestive Issues DNA silencing Neurotransmitter balance Metal Detoxification
Inflammation Membrane fluidity Energy production Protein activity Myelination Cancer prevention
Because it’s involved in so many processes, inefficient function or mutations along the methylation pathway can result in a wide range of conditions, including the following:
Aging Allergic reactions Alzheimer’s Anxiety Arthritis Autism Bipolar disorder
Bowel dysfunction Cancer CFS/FM Chronic bacterial infections Chronic viral infections Cytoskeletal breakdown Diabetes

Down’s syndrome Heart disease Herpes Huntington’s disease Language and cognition impairment Leaky gut
Leaky gut syndrome Metal toxicity Miscarriage Mitochondrial disease
Neural tube defects Pneumonia Psoriasis Renal failure
Rett’s syndrome Schizophrenia Seizures Sleep disorders Systemic Lupus Erythematosus (SLE) Thyroid dysfunction

Let’s look at a sampling of the issues arising from inadequate methylation.

Repairing and Building DNA

One extremely crucial function of methylation is its role in the synthesis of DNA. DNA carries the blueprint, or genetic coding, needed to build the components of living organisms. Every time your body needs to repair the gut lining, or create an immune cell to respond to an immune threat, or to heal when you have cut yourself, you need to synthesize new DNA. But without a functioning methylation cycle, your DNA is not going to replicate properly. Why?

DNA is composed of building blocks called nucleotides, chemical compounds that contain four bases—cytosine, guanine, adenine, and thymidine. Several of the enzymes involved in the creation of these bases are a part of the methylation cycle. For instance, one gene has the very long name of methylenetetrahydrofolate reductase (commonly abbreviated as MTHFR). As you can see from the beginning of its name, MTHFR contains a methyl group. That is why a mutation in the gene responsible for making this enzyme may impair the ability to make the necessary elements for DNA. As we will see later, the base most affected by the lack of methylation is thymidine.

Undermethylation is also responsible for what is known as “trinucleotide repeat disorders.” The bases are arranged on our genes in sequences of three, or “trinucleotide repeats.” But unless those three-base sequences are methylated, they will repeat themselves as much as a thousandfold, creating various serious conditions, such as Friedreich’s ataxia, Fragile X and Huntington’s disease, depending on which sequences are repeated. When there is insufficient methylation and these three-base sequences repeat themselves into very long sections, they also attract the limited number of methyl groups that are available, increasing the risks for these disorders.

Very similar to DNA is RNA, which is crucial to building proteins, transferring the information carried by your DNA and regulating your genes. In fact, RNA is even more abundant in your body than DNA. Just to keep your DNA constant—without even mentioning the amount of nucleotides we need for RNA, the body requires enormous amounts of nucleotides, the building blocks of DNA and RNA. One reason I suggest the use of RNA and nucleotides as supplements is to take some of the burden off the body, so that instead of the body needing to utilize the methylation cycle to make so many of its own building blocks, we supply some of those building blocks, leaving methyl groups for some of the other important roles we have mentioned. For example, when certain cells can’t make enough of the bases adenine and guanine on their own to keep up with the body’s needs, we are able to take some of the burden off the system by supplying RNA. Later in this book I’ll discuss the special RNAs (and nucleotides) we use to support the body.

The use of RNAs and other supplements can help to provide the body with what it needs even in the presence of mutations. Nearly all children with autism have impaired function (the blockage on the highway) caused by the genetic mutation in MTHFR along with mutations in other genes in this pathway. Now, suppose that a child also has had environmental exposure to thimerosal, a mercurycontaining preservative used in many vaccines, which can also interfere with methylation. When both things occur together, they interact and further weaken the body’s ability to perform key functions.

Here’s another example: Another one of the enzymes critical to methylation, methionine synthase (MTR), requires an active form of vitamin B12 in order to function properly. The body’s ability to supply B12 can also be impeded by the MTHFR mutation. Further, research has shown that mercury adversely affects this reaction, and so it can impede DNA methylation. With both the mercury present in the thimerosal and the MTHFR mutation you now have two accidents (the MTHFR mutation and mercury exposure) on the highway, causing a roadblock (impaired MTR function.) It’s going to be that much harder to clear two accidents and a roadblock than it would be to clear just one accident in order to restore adequate methylation function. The end result? Greater difficulty in creating the building blocks for DNA.

Immune Function

Methylation also plays a key role in the ability of our immune system to recognize foreign bodies or antigens to which it needs to respond. Whenever there is an assault on the immune system, the body must synthesize new T cells, which belong to your white blood cells. These cells help fight viral and parasitic infections, and are also needed to help to control B cells, which produce antibodies. Due to mutations in the methylation pathway, you may lack the ability to produce the methyl groups necessary for making new T cells. When that occurs, there is an increased tendency to produce B cells, which may therefore result in an autoimmune disorder. When I and my practitioner colleagues look at the blood work of many of the children, we often find these kinds of imbalances—they have too many auto-antibodies, not enough of a T-cell response, and too much of a B-cell response. I have seen several cases in which the level of auto-antibodies has declined after proper methylation cycle supplementation.

Methylation of DNA also regulates immune cells. Immune receptor DNA is initially in the “off” state and remains that way until the immune cells need to differentiate in order to respond to an intruder. As you will learn in greater detail below, at that time the DNA loses its methyl groups in a regulated fashion and the DNA is turned “on.”

As we have just seen, methylation is generally correlated with the silencing of genes. But research has also shown that when genes are not methylated at specific points, the immune system can be tricked into reacting against itself.

So, to sum up, methyl groups help turn your genes on and off. They also help determine the ways your immune system reacts. Unless methylation is operative, the immune system may react when it’s not needed, creating autoimmune disorders, or fail to respond to actual threats when it is needed.

Digestive Issues

The functional areas impacted by improper methylation are in a dynamic relationship with one another—that is, they are mutually interactive. So it is with the relationship of your immune cells to digestive issues. Since many of your immune cells reside in the digestive tract, there’s a close relationship between methylation, immunity, and such digestive problems as leaky gut, allergies, and various forms of digestive distress that the children commonly experience. Briefly, if methylation is low and T cell production is low, then histamine levels tend to be high. Histamine is linked to inflammation, a contributing factors to leaky gut as well as allergies.

 Methylation  T Cells  Histamine
 Inflammation

With the underactivity of T cells, B cell activity can take over, which can lead to autoimmune issues like allergies and food sensitivities. That’s why so many children with autism benefit from a gluten-free, casein-free diet. While some practitioners working with children with autism recommend this type of diet, knowing the underlying biochemistry helps explain why it often proves helpful.

DNA Silencing

Methylation is critical to what we call “gene expression.” Although your genes never change, they can be active or inactive, as we saw earlier in this chapter. The body turns on (expresses) a gene, or turns off (silences) a gene. Whether it’s preferable for the body to either express or silence a gene depends on its role.

How does this work? To regulate our DNA, to help to turn it on and off, the body adds methyl groups to the DNA strands. If you think of your DNA as a charm bracelet, it’s as if the methyl groups are hanging off the bracelet at different points. Wherever there is a methyl group on the bracelet, those genes will be silent, and wherever the methyl group is removed, those genes will be expressed. A lack of proper methylation means that DNA that should be quiet can be expressed, and this may cause specific changes in the body. For example, many children change hair color as they grow older. A child with blonde hair may change into a brunette. This is because the gene for brown hair, which was switched off, becomes switched on. Lactose intolerance is another example. You may be able to easily digest milk as a child, but once your gene for lactase, the enzyme for digesting milk, is switched off, you no longer can.

Of course, gene expression or silencing can have far more significant consequences than hair color or lactose intolerance. Take the measles, mumps, and rubella (MMR) vaccine as an example. When viruses (such as those contained in this vaccine) are inserted into your genome, it’s not healthy for those viruses to be “turned on” and become active. However, without adequate methylation, that’s exactly what can happen. Unless you have adequate methyl groups that attach themselves to the viruses to silence them, they can become active.

What occurs if these genes are activated? Instead of evoking an immune response that grants resistance to measles, mumps, and rubella, as they are supposed to, these vaccines can produce an entirely different, unwanted effect. The recipient of the vaccine can become subject to chronic infection from these activated viruses that now, like a Trojan Horse, have taken up residence in the body. In a similar way, methylation plays a role in carcinogenesis, the growth of cancer cells. If, due to inadequate methylation, DNA isn’t regulated properly, then it doesn’t send the right signals, and cell division can become uncontrolled, resulting in cancerous growth.

When there is improper methylation, not only will the DNA bracelet lack the methyl groups that can turn your genes on and off, but the bracelet itself, the actual DNA links on the bracelet, will not be as stable.

Neurotransmitter Balance

Neurotransmitters are chemicals that control the signals between a neuron, a nerve cell, and another cell. Impaired methylation results in a lack of the components needed to generate neurotransmitters like serotonin, which regulates mood, emotion, and appetite, as well as problems converting serotonin to melatonin, so we can sleep at night. Many of the children I see have difficulty sleeping because they can’t utilize their bodily stores of serotonin and convert it to melatonin. Adults with chronic fatigue and fibromyalgia also frequently complain about sleep issues. Imbalances in the methylation pathway will also affect the neurotransmitter dopamine. Proper dopamine signaling requires that the dopamine receptor be able to move freely within the cell membrane. The dopamine receptor, located on the cell surface, is like a fishing pole that catches dopamine. Methylation supports receptor activity by keeping the phospholipids in the cell membrane fluid. Membrane fluidity also aids proper signaling of the immune system and protects nerves from damage. The symptoms of diseases such as ALS and Alzheimer’s disease result from nerve damage.

In the methylation pathway, one crucial component for neurotransmitter balance is the component, S-adenosyl methionine, or SAMe (pronounced “sammy”). SAMe is the most active methyl donor in your body, bringing methyl groups to numerous chemical compounds in your body. It also acts upon the neurotransmitters by changing them into other needed compounds. If we don’t have sufficient SAMe—or if SAMe can’t be recycled due to weaknesses in the methylation cycle, this can result in imbalances in our neurotransmitters, which in turn can impact mood, focus, sleep patterns, and a range of behaviors.

How We Use SAMe

  • To convert serotonin to melatonin, which supports the ability to sleep
  • For glutathione synthesis, which is critical to the body’s ability to detoxify
  • In the formation of many proteins, including myelin, the nerve sheaths that are so important to proper nerve firing
  • In the creation of CoQ10, creatine, and carnitine, compounds essential to the work of the mitochondria, the energy factories of our cells
  • To convert the neurotransmitter norepinephrine into epinephrine, (also known as adrenaline)

Together norepinephrine and epinephrine regulate the fight-or-flight response and, along with dopamine, are critical for attention and focus. That’s why psychostimulant medications such as Ritalin, Dexedrine, and Adderall are prescribed to people with ADD to help increase levels of norepinephrine and dopamine. In the neurotransmitter test results for children, I often see excess norepinephrine.

Because there’s not enough SAMe, with its methyl groups, it’s a challenge for the children to convert sufficient amounts of it to epinephrine. This is one contributor to ADD behavior. In addition, every time the body makes norepinephrine, it automatically reduces the level of the neurotransmitter dopamine, which is, I believe, one of the critical features for recovering language in children with autism. That’s why it’s important to address both these factors together through supporting methylation function.

The methylation pathway not only has to produce SAMe, it also has to recycle it. Once SAMe has given up its methyl groups to help create neurotransmitters, it is then “recycled”—that is, re-methylated. After SAMe has received its new methyl groups, it can perform its job all over again. Because of its essential role in reactions involving neurotransmitters, it’s not surprising that a lack of SAMe plays a role in neurodegenerative conditions. Due to methylation pathway weaknesses, some people can neither produce nor recycle SAMe. Fortunately, we can supplement SAMe to bypass mutations and attain its many benefits.

Metal Detoxification

Certain metals are referred to as “heavy” because they have a high atomic weight, at least five times greater than that of water. Not all heavy metals are bad. In fact, the body needs about seventy friendly trace-element heavy metals. Zinc is a common metal that is needed for a number of reactions that occur daily in the body. However, in addition to the heavy metals that we need in our bodies, there are twelve heavy metals that are poisonous to humans, and four in particular—lead, cadmium, mercury, and arsenic—that are especially toxic, even in low concentrations. Nickel, thallium, and tin, among others are also toxic when found in high amounts in the body. Through its publications, the Environmental Protection Agency recognizes our increased exposure to heavy metals. Not all toxic metals are heavy. For instance, high levels of aluminum in the body can cause a range of negative effects, and while aluminum is a toxic metal, it is not a heavy metal.

Increasingly, through industrial and agricultural waste, these metals have entered the air and soil and water and are now present in the food supply. The toxic metals gather in the soft tissues and bones of the body and contribute to the epidemic of degenerative illnesses we see today globally, and in all age groups. They begin to accumulate with the amount you get from your mother in utero, and continue throughout out life.

Common sources of heavy metals include:

  • Inhalations from metals released into the air from industry and pollution
  • Consumption of metals in foods (such as mercury in fish)
  • Absorption of metals used as ingredients in skin and body care (such as aluminum in deodorants)
  • Use of medications containing metals
  • Injection of metals via vaccinations

Because these metals tend to carry a positive charge, they combine easily with negatively charged molecules to form complexes.

How, exactly, do heavy metals overload your body? In the walls of your arteries, these metals can impede the normal flow of blood. In your adrenal glands they can reduce the production of hormones and can cause premature aging, stress, lowered sex drive, and aggravation of menopause. In your cells, they may interfere with a wide range of metabolic processes. They can cause problems such as depression and impair your ability to think clearly. They can aggravate conditions like osteoporosis and hypothyroidism. High levels of metals also impair myelination, the process of coating the nerves, resulting in misfiring. Memory and cognition are therefore directly affected by metal toxicity.

But the most serious problem, which I’ll address more fully in the next chapter, is that they contribute to the weakening of the inner biochemical environment of your body. As a result, opportunistic bacteria, viruses, parasites, and fungi are able to thrive in your body creating a dual challenge. That’s why the programs offered later in this book will help support the detoxification of both metals and microbes.

Metals can be extremely difficult to remove, and sometimes their presence cannot be easily determined by testing. One reason this occurs is that some metals, like mercury, can be hard to detect as they may be tightly associated with virus or bacteria in your body. This is another example of the interaction of two accidents on the highway—metals and microbes (viruses and/or bacteria). Alone, each can be an issue, but together they may have an additive effect, just as two accidents on the same roadway can have a greater impact on traffic flow than two individual accidents on different highways. If, due to improper methylation, this situation does occur, then metals and microbes can inhabit your cells together, and the former may not be easy to detect. However, using the approach outlined in this book, when we first support the methylation cycle and next address infections, we often see an excretion of metals as well, traceable through standard biochemical testing.

Many of the symptoms we see in autism resemble those of heavy metal toxicity. That is why some doctors treat autism through metal chelation (binding) and detoxification, and as a result of these treatments we often see improvements in cognitive function, speech, and other areas of functioning. Because of this empirical confirmation, detoxification has become a major focus in the holistic approach to autism and other disorders.

However, not all physicians are well versed in the rationale and methods of detoxification, and not everyone can accept the image of the body’s being full of toxins. Let me assure you, we are exposed to them, and they remain unless we successfully detoxify. Certain bodily pathways help us to do that. A growing body of genetic research clearly shows that a variety of genes serve a detoxification function and that specific genetic impairments in those genes may increase the risk of disease.

A number of agents are currently utilized for chelation of heavy metals, including DMSA, DMPS, EDTA, glutathione, alpha lipoic acid, and garlic. Interestingly, each of these agents also has antiviral capabilities. Garlic is well known as an antiviral, antifungal, antibacterial nutritional supplement. Glutathione is one of the body’s most important defense mechanisms against viruses. There are examples in the literature of EDTA eliciting virus from cells. DMSA, which is widely held as solely a mercury chelator, has been described in the medical literature as having antiviral activity, more specifically antiretroviral activity (measles and mumps are retroviruses). DMSA is commonly used to help chelate heavy metals and for detoxification with children exhibiting autistic behavior. However, it is important to realize that DMSA has been shown to trigger the inflammatory mediator TNF alpha, so it is important to use caution and actively add agents that can effectively reduce and/or control inflammation when using DMSA. DMPS is also listed on the NIAID therapeutics database as showing antiviral activity against HIV. Both DMSA and DMPS have potential side effects and should be used with caution and under the care of a doctor familiar with chelation protocols.

It is possible that all of these chelating agents act to both chelate heavy metals as well as to trigger the removal of chronic virus-containing metals from the body. The “detox rash” with which most parents of children with autism are familiar may in some cases be a viral rash, as chronic virus is eliminated from the body along with the excretion of toxic metals. To use the example again of automobile accidents tying up traffic, this would be like removing two disabled vehicles at one time, and letting through the flow of cars.

Methylation and Detoxification

As I just mentioned, one common method for removing metals used by some doctors is a process called chelation. Chelating agents like EDTA bond chemically with the metal ions and make them water soluble, so they can be carried away by the blood and excreted harmlessly. But some of these toxic metals are so bound up and sequestered in the body that traditional chelators cannot get to them. An important part of the protocol presented in this book is a proprietary approach to metal detoxification that allows us to target these sequestered metals, along with microbes in the body. The success that this new approach is providing is seen in clinical improvements, along with significant increases in urine and/ or fecal excretion of toxic metals. These results suggest that these chronic infections efficiently bind toxic metals in the body where no chelating agent seems to be able to effectively remove them. These results are observed even with patients who, it was thought, did not have significant levels of mercury. Yet, in these patients, there is a substantial release of mercury and other toxic metals as the viral and bacterial load is reduced, and patients’ symptoms improve dramatically.

One major reason that we need a well-functioning methylation cycle is that the methyl groups the cycle produces can help in the removal of these metals. For example, with arsenic, methyl groups do this by directly combining with these sequestered toxins and removing them. Most of the methyl groups used for metal detoxification are donated by SAMe. However, you need a well-functioning methylation cycle to produce all the components (including SAMe) that create sufficient methyl groups. Overall, having a functional methylation cycle can also help to reduce the bacterial or viral load, indirectly aiding in toxin excretion. However, with mutations in this pathway, the body may have difficulty addressing toxin excretion, which is why testing and supplementing for genetic weaknesses on the pathway can be so important.

On the other hand, the fact that methylation is so necessary for detoxification but environmental toxins can disrupt methylation creates a toxic catch-22.

For example, cadmium inhibits the methylation of phospholipids, which affects your cellular membrane function. And arsenic, nickel, and chromium can cause overmethylation of DNA, which can result in turning “off” important regulatory genes, such as tumor-suppressor genes. Genetic testing reveals that some people have a tendency to produce insufficient numbers of methyl groups. Obviously, this factor alone reveals why a one-size-fits-all treatment approach is not helpful. That’s why testing is so vital.

Researchers have found that many children with autism do not make enough of the antioxidant glutathione, which is also crucial to removing toxins from the body. When the methylation pathway is dysfunctional, the body can’t produce sufficient glutathione. Further, if the cellular mitochondria are dysfunctional— as they are in some children with autism—they will produce more free radicals as a byproduct and deplete the body’s glutathione. Toxic metals such as aluminum can decrease mitochondrial energy, contributing to mitochondrial dysfunction. What’s more, higher bacterial loads can cause the body to retain aluminum. So, first, aluminum and bacteria can interact to decrease mitochondrial function; impaired mitochondria create a greater need for the anti-oxidant glutathione; however due to impaired methylation the body can’t produce the glutathione it needs—another example of the multifactorial, multilayered nature of this condition.

Inflammation

Inflammation has been implicated in a host of health conditions. There is a reciprocal relationship between methylation and inflammation, almost as if they were on a seesaw: increased inflammation will tend to decrease methylation and vice versa.

Let’s see how this works. IL6 and TNF alpha are two bodily biochemicals that lead to inflammation. They frequently arise in response to stress. Higher levels of these inflammatory chemicals exacerbate low methylation status.

Under-methylation contributes to several kinds of inflammation in your body:

  • Heart and vascular inflammation
  • Autoimmune disorders
  • Neurological inflammation

Heart and Vascular Inflammation

Proteins, especially meats and dairy, contain the amino acid methionine. Notice the prefix “meth”—indicating that methionine contains a methyl group. At a certain point, methionine converts to SAMe, which as I mentioned earlier is the biggest methyl donor in the body. SAMe travels around providing methyl groups to hundreds of reactions, and enables many processes to take place. Once SAMe has delivered its methyl group, it becomes homocysteine, which is then ready to transform itself back into methionine, so the process can begin again. But supposing there are too few methyl groups and homocysteine can’t covert back to methionine? In that case, homocysteine levels build up in the body, producing inflammation, heart disease, poor circulation, degenerative and other health conditions.

To prevent congestive heart failure, the body needs adequate levels of CoQ10. Clinically, CoQ10 has been used in the treatment of angina, heart failure, and after coronary artery bypass and cardiomyopathy—inflammation and weakening of the heart muscle. The synthesis of CoQ10 requires components of the methylation pathway—in particular, adequate levels of SAMe. Elevated homocysteine levels bring an increased risk of heart disease. Researchers have seen this increased risk in those with a particular mutation, C677T, in the gene MTHFR, which is located on the methylation pathway. Many of the children have this mutation, and their parents may have it as well.

Autoimmune Disorders

Arthritis, Lupus, Diabetes

Part of what I believe often occurs with autism is too much emphasis on the B-cell immune response, which is mediated by antibodies, relative to the cellmediated response, which is mediated by the T cells. This may be due (at least in part) to the fact that the methylation cycle is needed to make new T cells. Unlike B cell clones, which are “set for life” so to speak, T cell clones need to expand “on demand.” This expansion requires the synthesis of new DNA and RNA, a task that in turn requires building blocks generated via the methylation cycle. A prevalence of immature T cells increases the inflammatory response if not properly regulated. This disregulation commonly occurs when there are adequate helper T cells to aid in the antibody response but a lack of enough suppressor T cells to control that response—resulting in autoimmune disorders like lupus, rheumatoid arthritis and type-1 diabetes.

Allergic Reactions

Histamines, as I mentioned earlier, cause allergic reactions when they are released in response to antigens. Histamine levels in your body are dependent on the methylation cycle because histamines are broken down, or deactivated, by receiving a methyl group. Impaired methylation therefore leads to abnormally high levels of histamine and increased allergic sensitivity, something we often see in children with autism.

Another factor leading to inflammation is inflammation itself. Chronic inflammation creates an undesirable feedback loop: improper functioning of the methylation cycle produces inflammation, while inflammation worsens the ability to methylate properly.

Neurological Inflammation

Excitotoxins are a significant contributor to neurological inflammation. These chemicals do just what they say—they excite the neurons to fire and ultimately lead to nerve cell death. This can occur over many years—by the time an individual experiences symptoms, the damage has been done. That’s why, in this program we take active steps to limit excitotoxin damage.

Excitotoxins occur naturally in the body, but they have also been added to our food supply in huge quantities in the last fifty years. Monosodium glutamate, aspartame, hydrolyzed vegetable protein, and other additives—all these excitotoxins stimulate your taste buds and mask the real taste of food. Commonly, they are added to enhance the flavor of artificial and processed foods, which wouldn’t taste very palatable without them; natural foods, in addition to their higher nutritional value, don’t require this form of flavor enhancement. Excitotoxins in food overexcite the neurons to the point where they become inflamed and begin firing so rapidly they become completely exhausted or die. Companies producing these excitotoxins sometimes claim that, since glutamate is found naturally and abundantly in the brain, additives that contain it, like MSG and aspartame, are “natural” and therefore not harmful. That is misleading, since you must take into account that, in the body, glutamate exists only in very, very small concentrations. When the concentration rises above this very minute level, your neurons can become overexcited and fail to fire normally.

Further, a wide variety of nutritional supplements contain glutamine or glutamate, while many consumers and practitioners remain unaware of its potential for harm in genetically susceptible individuals. It’s my recommendation that you read labels on food products and supplements to determine whether they have added glutamate. If they do, eliminating them is one of the very first steps in this program, as detailed in Part Two of the book. While there are many steps in the program, as well as individual variation in how each person must go through it, one thing everyone without exception can safely do is limit neurological inflammation by eliminating excitotoxins in the diet.

In addition to food additives and supplements, bodily glutamate load can also increase due to mutations in the methylation pathway. If the methylation pathway is not functioning optimally, folate—a polyglutamate—sits around unused and can break down into glutamate. This, by the way, may also have the effect of increasing intelligence, because to handle that excess load of glutamate, you increase the number of your glutamate receptors, and this can correlate with high intelligence—something I find in many of the children I work with. So mutations in the methylation pathway drive both the excitotoxin damage and may also help to explain the high intelligence observed in children with autism. Through this program, my aim is to foster the intelligence, while limiting the damage.

Membrane Fluidity

Why do we need our cell membranes to be permeable? The cell membrane surrounds your cells like a protective skin and selectively regulates what enters and exits. Certain proteins embedded in your cell membranes also act as signals between cells, coordinating cell actions like growth, tissue repair, and immune response. Still other proteins on the surface of the membrane, known as markers, identify cells to each other. For all these subtle processes to work properly, your cell membranes have to have exactly the right composition—the right amount of fats, or lipids, in combination with proteins and phosphates. Think of the signaling and marker proteins as large rafts in a sea of phosphlipids. If the sea is fluid, then the rafts can move around as needed. But if the sea is solid, like Jell-O, then the rafts cannot move and ferry around what they are intended to transport. Here again, methylation is a crucial player. As mentioned earlier, the methylation of phospholipids in the cell membranes is critical for membrane fluidity. Without proper methylation, due to mutations in the methylation pathway, there may be insufficient methyl groups necessary for this task. As a result, membrane fluidity is directly affected by improper methylation, and signaling between cells may be impaired.

Energy Production

All cells need to produce energy to survive, and they produce it via a process called the Krebs cycle, also known as the citric acid cycle. This metabolic pathway produces the energy “currency” of the body, known as ATP. The Krebs cycle takes place within the cell in an organelle known as the mitochondria. Think of mitochondria as a cellular power plant, or the engine on a train—you have to keep shoveling coal into it to keep the train moving. The Krebs cycle is closely connected to the methylation cycle, and any impairment of one impacts the other. Essential to the action of the mitochondria are carnitine and CoQ10, both of which are dependent on the methylation pathway. That’s why at certain phases of the program, people often supplement these two bodily components.

Carnitine

L-carnitine is the compound that transports long-chain fatty acids into the mitochondria so they can be broken down for energy. In fact, it is one of the few natural materials known to allow fats to cross the mitochondrial membrane, so it is crucial to fat metabolism. This is important because mitochondria fatty acid oxidation is the main energy source for heart and skeletal muscle. The synthesis of carnitine in the body begins with the methylation of the amino acid L-lysine by SAMe, which demonstrates the close interrelationship between the Krebs and methylation pathways.

Coenzyme Q10

Coenzyme Q10 is an enzyme essential to the production of ATP—it’s involved in 95% of the energy-producing reactions in your body through its role in electron transport. CoQ10 delivers electrons to precisely the right places during the formation of ATP. CoQ10 is also a very powerful antioxidant, which helps to protect the mitochondrial membrane and cell walls from attack by free radicals. And just as with carnitine, the synthesis of CoQ10 by your body depends on the methylation pathway.
Low muscle tone and extreme muscle weakness, which we often see in children with autism and adults with chronic fatigue, may in part be due to decreased mitochondrial energy—and, as we will see below, to myelination problems resulting from reduced methylation cycle capacity.

Protein Activity

I’ve already discussed how DNA, which contains your genetic information, is regulated by methyl groups—CH3 groups—that attach to parts of the DNA and turn genetic information on and off. If methylation is impaired, then the wrong information may be expressed, or information that should be expressed, isn’t. Through the intermediary work of RNA, the DNA in your body is used to create specific proteins, that is, the building blocks for your cells and tissues. RNA may be “arm” or “lip” or “liver” RNA, that provides the blueprint for building those specific proteins. Each of them is made up of amino acids in specific combinations, and here again methylation is crucial with regard to how those proteins are arranged. Impaired methylation means trouble at both ends of this process—at the DNA end and in the formation of the proteins themselves.

Myelination

Think of your nerves as wires. Without insulation, the wires will short circuit. In the same way, unless your nerves are coated, they cannot transmit messages accurately and efficiently. Methylation is directly tied to the production of the myelin that coats the nerves, a process called myelination. The most commonly known myelination defect is multiple sclerosis, an ailment in which antimyelin antibodies are made; antimyelin antibodies are frequently found in children with autism as well. Myelination requires methylation.

Without adequate methylation, the nerves can’t myelinate in the first place. Second, they can’t remyelinate after insults such as viral infection or heavy metal toxicity. And without myelination or remyelination, there is inadequate “pruning” of nerves, leading to excessive, dense, and bunched wiring, unused neural connections, and the misdirection of nerve signals.

The Role of Methylation in Health Conditions

Although it’s not within the scope of this book to delve deeply into the role or treatment of the wide range of adult disorders impacted by the methylation cycle, I’ll touch briefly on a few of them here. Some researchers have focused on specific genes in this pathway because of their possible connection to certain adult conditions, prevalent in our society today.

Cancer

Undermethylation of the entire genome is referred to as “global hypomethylation.” Global hypomethylation, when paired with overmethylation of specific, repeated genes, is associated with both aging and cancer. Both undermethylation of tumor-causing genes (genes that should be switched off but are switched on) and overmethylation of tumor-suppressing genes (genes that should be switched on but are switched off) are contributing factors to cancer. Improper methylation can also contribute to the inability to inactivate estrogen, and excess estrogen has been linked to an increased susceptibility to hormone-sensitive cancers. Epidemiologic and mechanistic evidence suggests mutations in the methylation pathway are also involved in colorectal neoplasia (colon cancer) as well as a number of other cancers.

Pregnancy Risks

Periconceptional supplementation to support the methylation cycle helps to prevent a wide range of potential risk factors in pregnancy, including miscarriages, neural tube defects, and others. That’s why in an ideal world, all parents considering conception would go for genetic testing first and support any defects to assure a healthy pregnancy, birth, and child. We know that mutations in the MTHFR genes of the methylation pathway, as well as mutations that lead to decreased B12, are risk factors for neural tube defects. Mutations in the methylation pathway, specifically methionine synthase (MTR), methionine synthase reductase (MTRR), as well as elevated homocysteine, are risk factors for having a child with Down’s syndrome.

It’s important to consider methylation pathway mutations when supplementing folate during pregnancy. Using folate during pregnancy helps to decrease the risk of neural tube defects. This does not change the DNA but has a regulatory effect on the ability of the DNA to be expressed, known as genetic expression, or epigenetics, which I’ve discussed throughout this chapter. Running a Nutrigenomic test to determine the appropriate form of folate is critical, because the wrong kind of folate can block the ability to absorb and use the right kind of folate. Although many supplements contain common folic acid, about 40% of people cannot use it and need to take a different form of folate. Genetic testing can reveal this.

Aging

Methylation pathways decrease in function as we age. DNA methylation is also known to decrease with aging. These age-related decreases in methylation can also lead to decreased methylation of T cells, which may, in part, explain changes in your immune function with age. Age-related decreases in methylation, for example, can result in increased levels of homocysteine, increasing the risk of arthritis, cancer, depression and heart disease. Increasing the body’s level of methylation through supplementation may extend healthy life span. A clearer idea of your specific methylation cycle mutations may help you to customize supplementation to bypass mutations for better methylation cycle function.

Infections, Bacteria, and Viruses

Viruses are very old—they’ve been around longer than humans, and so from an evolutionary standpoint, have had a lot of time to learn how to trick the body. Like cells, viruses have a membrane. But viruses are basically parasites, with proteins sticking up from their surface that snatch components from your cell membranes, or fuse with them.

Remember, that methylation is necessary to silence viruses. When viruses build up in the system, they can hang onto and store heavy metals. When we look at the possible interconnection between vaccinations and autism, it’s evident that vaccinations can deliver viral and metal loads into the newborn infant and developing baby and child. The rising rates of autism indicate that, for a variety of reasons, a growing number of children may not be able to tolerate those loads. Instead of instigating the desired immune response, the child’s immune system is literally overwhelmed. Whether these responses are due to higher environmental exposures to these toxins or certain weaknesses in the child’s methylation pathway, supplementing with the appropriate nutrients prior to vaccination may perhaps compensate for that increased exposure or weakness. With that support, the child’s immune system may be able to produce the desired immune response, rather than become overwhelmed. Moreover, knowing the risk factors may help parents make decisions to delay vaccinations or to avoid vaccinating at times of higher risk, as, for example, when the child’s immune system is already addressing an infection or other health challenge.

Methylation: Nature vs. Nurture

A July 9, 2005 article in Science News reported that, although identical twins have identical DNA, they often have differences in a number of traits, including disease susceptibility. This study suggests that as identical twins go through life, environmental influences affect which of their genes are actually turned on or off. Methyl groups attach to DNA like charms on a charm bracelet—this modification of the DNA is known as gene expression, or to use the more scientific term, epigenetic regulation. The combination of the environmentally determined addition of these “charms” to the bracelet of DNA, combined with inherited DNA changes or mutations, lead to an individual’s susceptibility to various health conditions. The scientist who headed this study, Dr. Manuel Estseller, said that “people are 50 percent genetics and 50 percent environment.”
This statement should give us some understanding as to why mutations in the methylation pathway can be so devastating. Mutations in the methylation pathway affect the “nature” half of the equation, the 50% of the pure genetic susceptibility; this would be analogous to defects in the links of the chain of our charm bracelet. But, in addition, because methylation is also necessary for the epigenetic modification of the DNA, methylation also affects the “nurture” side of the equation as well, the environmental 50%. In other words, genetically inherited mutations in the methylation pathway cause problems in the links of the DNA bracelet and environmental effects create a problem with the ability to put charms (methyl groups) on the bracelet. Problems in the methylation pathway therefore can affect 100% of our susceptibility to health conditions. This is why it’s critical for health maintenance to understand where our weaknesses in this pathway reside and then supplement appropriately to bypass these mutations. By bypassing mutations in this way, we are using the “nurture” side to both optimize “nurture” and counteract any shortfalls in “nature.”

A second study that has also addressed the nature vs. nurture question used animal models. Researchers were able to show that the adult response to stressful situations was heavily influenced by the interactions the animals had as pups with their mothers. Those pups with higher levels of care showed differences in the methylation patterns of stress-related genes when compared with pups in the lower-care test group. This work suggests that there is a bridge between “nature and nurture” and that nurturing can influence DNA methylation. However, nurture alone cannot be the answer. To use our analogy again, proper nurturing can influence the epigenetic modification of DNA, that is, it can affect the number of charms on the bracelet. But, once again, genetic mutations in the DNA sequence (the bracelet) itself will affect the overall methylation capacity in the body. Without the mechanisms to produce the methyl groups in the first place, all of the nurturing in the world will not be able to overcome the lack of ability to methylate. In other words, if the body cannot produce charms for the bracelet, how easily you are able to attach them becomes a moot point. Nutrigenomic support to bypass these mutations is necessary to address the weaknesses in the DNA that would result in reduced capacity in this pathway.

Perhaps the easiest way to explain the difference between genetics and epigenetics is to use a computer analogy. If your computer keyboard has a broken M key, when you type, that letter will always be missing from any words that include it. The mutations we look at are like the words with the missing M, and that will not change over time. That is one reason the Nutrigenomic profile you get today is so useful—the information will be applicable five, ten, or fifty years from now. Just as the broken M will not magically fix itself, your actual genetics and mutations will not change. But suppose you ran a spell-check after you typed a document. The spell-checker would find misspelled words and propose substitutes for them. For ister it would ask you if you mean mister, and so on. Epigenetics is like the spell-checker. It can change over time, and it can compensate for what is missing. But the spell-checker itself relies on methylation and proper nutritional support to function properly. This highlights why this pathway is so important. Using this analogy, looking at SNPs in the methylation cycle helps us to determine which keys on our computer are broken as well as to be sure that our internal spell-checker is working properly.

It’s also important to keep in mind that the factors that impact the expression of our basic DNA have a broader truth and application throughout all areas of bodily function. On this program, my goal is to give you information and tools so that you can:

  • Optimize function through bypassing genetic weaknesses
  • Provide the supports and nutrients the body needs
  • Reduce and eliminate the impacts of toxins and substances that cause bodily harm

With this program, you access ways to optimize both nature and nurture and restore health.

Meet the SNPs

Throughout this book, I’ve shown you the interplay of the various factors that, taken together, can contribute to autism as well as other health conditions. What differentiates the program offered here from others is the ability it gives you to fine-tune your approach based on genetics and biochemical individuality, as captured via the Nutrigenomic testing of key genes on the Methylation Cycle. Key to following the program are the results of the Nutrigenomic test (available at www.holisticheal.com). Remember that, by itself, the fact that you or your child carry a specific mutation does not mean that particular enzyme is not working correctly, at 100%: these markers are indicators of potential problem areas, which can manifest as a result of other influences.

Gaining familiarity with your child’s (or your own) test results is a bit like learning a foreign language. In this section of the book, my aim is to begin to introduce you to that language, so let’s review some key points.

In undertaking Nutrigenomic testing, our goal is to identify which genes along the pathway have single nucleotide polymorphisms, or SNPs (pronounced snips). To help provide a sense of what you may find when you get back test results for you or your child, I’ll offer a brief introduction to some of these SNPs. A more comprehensive explanation of all of them (and how they interact) can be found in my book, Genetic Bypass. I also continually update my findings in the online chat room, so please make sure to check there as well.

Why Gene Testing?

Because of recent breakthroughs, we can now test for specific areas of genetic weaknesses. Yet, despite the great opportunity for improvement offered by understanding and addressing SNPs, this potential remains untapped for a variety of reasons. One reason is that people have felt concern about the potential misuse of genetic screening to discriminate in employment or insurance coverage. However, a federal law, the Genetic Information Nondiscrimination Act of 2008 (GINA), now offers protection to those who want to make use of this new area of science.

Other people are fearful of finding out their exact genetic weaknesses, particularly when gene testing may reveal the potential for illnesses for which there is no effective treatment. I understand this concern, and I also do not believe in testing if we have no positive way in which to address results we receive. I believe in focusing on genetics in pathways in which we do know how to address mutations that are found. I consider it a waste to possess this technology and fail to use it to our advantage. I think these kinds of assessments should be made in the context of following the program and using nutritional supplementation. In other words, targeted genetic testing is appropriate in my view when it fine tunes the approach, rather than merely serves idle curiosity.

That’s why I’ve been using my knowledge of biomolecular Nutrigenomics to define ways to address genetic weakness through supplementation, RNAs, and other approaches. Once the molecular pathways affected by specific SNPs are known, Nutrigenomics uses combinations of nutrients, foods, and natural ribonucleic acids to bypass these mutations and restore proper pathway function. With this approach, you’re not just giving yourself or your child a one-size-fitsall array of supplements without some prior indication that this particular child is going to benefit from taking them. The use of genetic testing allows us to not only know our genetic profiles, but to take full advantage of that knowledge.

This is commonly done with a simple saliva test, cheek swab, or finger prick blood sample. I prefer the blood sample because I find the results to be more consistent and accurate. So let’s say you decide to go ahead and test yourself and your child. What exactly will the test reveal?

The Alphabet of Genes

In Nutrigenomic testing, we are able to identify changes in the order, or what we sometimes call the “spelling,” of the genetic bases. These spellings are a shorthand used by scientists which deploy the letters A, T, C, and G to designate each of our four genetic bases—adenine, thymine, cytosine, and guanine—that combine in various ways. These four bases are organized into a particular sequence to create or “spell” every single one of the genes in the body. Taken together, these bases make up all our DNA.

To see how we identify mutations, let’s look at an example in which DNA fragments from two individuals vary by just a single nucleotide. In other words, one “letter” in the gene sequence differs from the norm. In our example, the difference occurs between the C and the T in the fifth position. Accordingly, Joan will have the gene sequence AAGCCTA, while Bill will have the gene sequence AAGCTTA. Scientists call these variations alleles. Most common SNPs have only two alleles. In other words, all the other “letters” in the sequence remain stable and unchanging. In our example, Joan has the most common gene allele, while Bill’s genetic sequencing contains the variation—the SNP.

What happens when you or your child has a mutation in a genetic sequence?

To understand this, let’s take a deeper look at the task performed by each gene. That task will differ depending upon the functional area that the gene impacts. A change in that gene will change the action of that enzyme, catalyst or activity. As an example, let’s say that we are dealing with mutations in genes that affect your enzymes. Enzymes do many different things. Certain enzymes join together to make components needed to perform a particular task. Other enzymes may break down one biochemical or transform it into another. Enzymes also govern the speed and efficiency with which these tasks are performed. For example, let’s say you’re sleepy one morning, so that when you went to make drip coffee, you forgot to use a filter. As a result, the grounds wind up in your coffee mug. Not good! In just the same way, if a group of enzymes that are supposed to filter out or address a harmful substance (like the inflammatory substance homocysteine) fail to do their job, you will wind up with more homocysteine than your body can manage.

Biochemical actions can also be slowed down or accelerated by enzymes. Many people would feel over-stimulated and have trouble going to sleep if they drank caffeine before bedtime. On the other hand, some individuals possess a biochemistry that can handle it. Just as the caffeine “speeds up” one’s energy, certain SNPs speed up (or slow down) certain biochemical functions. Accelerated activity can be more efficient, or it can produce undesirable effects. For example, speeding up certain neurotransmitters can result in stims. On the other hand slowing down activities can also be problematic, causing sluggish reactions. By identifying the presence of a SNP, we can compensate for it, and give the body the support it needs to perform its tasks successfully.

SNPs and the Methylation Pathway

In this book and in my overall approach, I focus on the methylation pathway, a central pathway in the body that is particularly amenable to biomolecular Nutrigenomic screening for genetic weaknesses. In practice, I have found that virtually all individuals carry at least a single mutation in the methionine/folate pathway. As a result of decreased activity in the methylation pathway, there is a shortage of methyl groups in the body that would otherwise serve a variety of important functions.

Defects in methylation lay the groundwork for further assault by environmental and infectious agents, resulting in a wide range of conditions, including autism. What makes the methylation cycle so unique and so critical for our health is that mutations in this pathway also have secondary effects on genetic expression. In other words, they affect all three of the factors that can lead to autism.

It’s my hope that this groundbreaking approach to optimizing function of the methylation pathway will serve as a model for working with genetic polymorphisms that affect other crucial biochemical pathways. Looking to the future of twenty-first-century medicine, I’m convinced that with time, research, and clinical practice, we can optimize the functioning of a wide range of other bodily processes as well.

How to Read the Nutrigenomic Test

In looking over this sample, please note that there are two copies of each gene, one from each parent. When both copies are identical, they are called homozygous and indicated by (+/+) or (-/-). With a few exceptions, these symbols mean that both have a particular mutation (+/+), or that neither has it (-/-). For example, MTHFR C677T(+/+) means both genes of the methyl tetrahydrafolate reductase enzyme have a mutation on the 677th position of the MTHFR gene, where cytosine is normally found. In this case, thymidine is substituted for cytosine. If only one of the two genes has cytosine and the other has thymidine, they are called heterozygous. This is indicated by C677T(+/-).

Although the (+ ) designation refers to a change from the norm, keep in mind that the definition of the norm can vary from lab to lab. This is why the call letter (the “C” in C677) is important. In cases where there is a discrepancy from one lab to another, the call letter can tell you that tests run from different labs have given the same experimental result, even though their reference standard was different.

To review, if an individual has a double (homozygous) mutation, its effects may be more pronounced than a single one (heterozygous.) However, by itself, the fact that an individual carries a specific mutation does not always mean that the particular activity (governed by that gene) is impaired. These markers are indicators of potential problem areas, which can then manifest either on their own or as a result of other influences. For example, while defects in the MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) gene can impair detoxification, toxins like mercury can compound the effect by decreasing MTR function—creating a corresponding decrease in the efficiency of detoxification. With both the genetic mutation and the exposure, you will tend to have more of a “double whammy” than either one on its own.

Basic SNPs

When you join my online chat room, you may notice that many of the parents post their child’s SNPs after their names. This is a way they share with one another the kinds of issues they are struggling with. Knowing your child’s or your own SNPs serves as the foundation for all the supplement recommendations as well as the steps you will follow on this program. Still, there is always an interaction between the recommendations and how each individual person responds. That’s why it helps to understand which functional areas are effected by mutations, so that you can try to assess your child’s (or your own) response to supplementation. It’s also vital to always introduce supplements slowly at minimal doses, to proceed gradually and work with your doctor or practitioner.

Now let’s take an initial broad overview of some of the genes, because the enzymes they produce are important for methylation cycle function. Once again, more complete information can be found in my book, Genetic Bypass

  • CBS (cystathionine-beta-synthase): regulates the enzymes that help to convert homocysteine into glutathione, a major antioxidant. Specifically, certain types of mutations in the CBS genes will produce more sulfur end products from the methylation cycle. In particular, individuals who have the CBS (+/+, or +/-) the homozygous or heterozygous variants may want to limit intake of sulfur-containing foods (like crucifers, garlic, and supplements, such as MSM as well as medications like DMPS.) Both the CBS homozygous and heterozygous mutations also have a higher risk for ammonia detoxification issues. (This mutation can also indirectly affect an enzyme called G6PDH, which has negative effects on blood sugar metabolism, red blood cell formation, and blood vessel stability, leading to easy bruising, bleeding, and broken blood vessels.)
  • COMT (catecholo-methyl-transferase): A primary function of the COMT gene is to help to break down dopamine. Dopamine is a neurotransmitter that is recognized for its role in attention, as well as reward-seeking behavior. It helps to cause pleasurable feelings that aid in reinforcing positive behaviors. COMT is also involved in the breakdown of another neurotransmitter, norepinephrine. The balance between norepinephrine levels and dopamine levels has been implicated in ADD/ ADHD; in addition, dopamine levels are important in ailments such as Parkinson’s disease. COMT is also involved in the proper processing of estrogen in the body. COMT (–/–) individuals break down dopamine effectively, and as such will be depleting methyl groups from the cycle and can tolerate more methyl group supplementation. With COMT (+/+), the homozygous mutation, the enzyme works sluggishly, essentially slowing down methylation of brain chemicals. In some situations, this is a better scenario for a child with autism, because that individual will tend not to use up excess methyl groups. However, with this profile, people may need to limit or avoid methyl donors, as excess methyl donors can lead to hyperactivity, irritability, and erratic behavior. Sensitivity to pain has recently been found to be correlated COMT (+/+) individuals.
  • MTHFR (methylenetetrahydrofolate reductase): The MTHFR gene products are at a critical point in the methylation cycle. One function helps to convert homocysteine into methionine, serving to keep homocysteine levels in a normal healthy range. Several mutations in the MTHFR gene have been well characterized as leading to increased homocysteine levels, which increases the risk of heart disease, Alzheimer’s, and cancer. Other genetic variations in MTHFR may play a role in the level of the neurotransmitters serotonin and dopamine, as well as the conversion of BH2 to BH4.
  • MTR and MTRR (methionine synthase/ methionine synthase reductase): These two gene products work together to regenerate and utilize B12 for the critical “long way” around the methylation pathway, helping to convert homocysteine to methionine. Mutations in MTR can increase the activity of this gene product so that it leads to methyl group depletion and greater need for B12, as the enzyme is using up B12 at a faster rate. The MTRR helps to recycle B12 for use by the MTR. Mutations that affect its activity would also suggest a greater need for B12.
  • NOS (nitric oxide synthase): The NOS enzyme plays a role in ammonia detoxification as part of the urea cycle. Individuals who are NOS (+ /+) have reduced activity of this enzyme. NOS mutations can have additive effects with CBS up regulations due to the increased ammonia that is generated by the CBS up regulations. Mutations in NOS may also play a role in dealing with proper processing of oxidized species. This may be important with respect to oxidized species generated by the mitochondria and impact energy, as well as play a role in the aging process and our risk for cancer.
  • SUOX (sulfite oxidase): This gene byproduct helps to detoxify sulfites in the body. Sulfites are generated as a natural byproduct of the methylation cycle as well as ingested from foods and preservatives we eat. Sulfites can also be used to prevent rust and scale in boiler water that is used to steam food, and even in the production of cellophane for food packaging. Because many reactions have been reported, the FDA requires the presence of sulfites in processed foods to be declared on the label. Difficulty in breathing is the most common symptom reported by sulfite-sensitive people. Sulfites give off the gas sulfur dioxide, which can cause irritation in the lungs, and cause a severe asthma attack for those who suffer from asthma. A person with SUOX (+/-) should be extremely careful with sulfur foods and supplements.
  • In addition to these major players, issues with other enzymes (and more are likely to be discovered) play a role in autism:
    ACE (angiotensin converting enzyme): Technically, the changes that affect the activity of this gene are not a SNP but a deletion (that means that a base is eliminated rather than substituted as occurs with a SNP) that can lead to elevated blood pressure. In animal studies, imbalances in this pathway were also correlated with increased anxiety and decreases in learning and memory. Increased ACE activity can also throw off the essential mineral balance in your system due to decreased excretion of sodium in the urine and increased excretion of potassium in the urine, provided the kidneys are functioning properly. Decreased potassium can also lead to fatigue and decreased energy production. This reaction is also tied to the stress response, in that situations of chronic stress can result in additional sodium retention and increased potassium excretion.
  • BHMT (betaine homocysteine methyltransferase): The product of this gene is central to the “shortcut” through the methylation cycle for converting homocysteine to methionine. The activity of this gene byproduct can be affected by stress, and may play a role in ADD/ADHD by affecting norepinephrine levels.
  • SHMT (serine hydroxymethyltransferase): This gene product helps to shift the emphasis of the methylation cycle toward the building blocks needed for new DNA synthesis and away from the processing of homocysteine to methionine. While DNA building blocks are important, mutations that affect the ability to regulate this gene product and interfere with the delicate balance of the methylation cycle may cause accumulations in homocysteine as well as imbalances in other intermediates in the body.
  • AHCY 1,2,19 (S adenosylhomocysteine hydrolase): These gene byproducts promote activity through the portion of the pathway that goes from methionine to homocysteine, effecting levels of homocysteine and ammonia. Therefore, the AHCY mutations will limit those activities, and may partially mitigate the effects of CBS upregulations, such that taurine levels remain moderate rather than elevated.
  • ACAT 102 (acetyl coenzyme A acetyltransferase): This gene byproduct contributes to lipid balance, helping to prevent the accumulation of excess cholesterol. ACAT is also involved in energy generation, through supporting the conversion of protein, fats and carbohydrates (from food) into energy. As a result ACAT mutations impact lipid balance, cholesterol levels, and energy levels, and may also deplete B12, which is needed for the long route around the methylation cycle.
  • PEMT (phosphatidylethanolamine N-methyltransferase): This gene interfaces between the methylation cycle and estrogen. People report that a modified form of the program used for autism also appears to benefit chronic fatigue syndrome (CFS), a condition that affects more women than men. In addition, in the methylation cycle, PEMT helps to convert phosphatidylethanolamine to phosphatidylcholine. Moreover, PEMT requires methyl donors for its activities and may therefore both impact (and be impacted by) methylation cycle imbalances.

Don’t worry! You don’t have to memorize these. As you proceed with the program, you will be hearing about these many times—and over time, they may become familiar to you—especially if you decide to take the test (for your child or yourself) and work with the program. Welcome to Nutrigenomic science! In Part Two we will use the foundational understandings we’ve built here, and show you how to use this information more specifically to follow the program.

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