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The Nerve of It All

HOW CHRONIC INFLAMMATION CRASHES YOUR MIRACULOUS HARD WIRING

If the central cell body were the height of an average man, its axon would be one or two inches in width and would extend more than two miles.

—THOMAS B. DUCKER, M.D.

Bite after bite, sip after sip, sugar is inflaming your blood vessels and nerves. This unrelenting inflammation incites stress in the body’s natural repair system, which results in fibrosis (scarring). The ongoing scarring systematically, pervasively, and insidiously causes compression in any area where blood vessels and nerves pass together through a tight area. I call this the Global Compression Theory^* and throughout the rest of the book, we’ll explore how and why this happens. As well as what you can do about it.

You Studied Nerve Cells in Middle School

Because this is a chapter about nerves, I first thought I should display detailed illustrations of various neurons—actual cells. Break it all down. Or tell you that such depictions always reminded me of a deep-sea creature or a scorpion, every detail serving a magnificent purpose: the cell body (soma) containing your DNA—with its tentacles (dendrites) that receive electrochemical messages; and the axon, a segmented tail-like appendage that whips those messages out to other cells in the body.

Yes, it is the cell that supports and nourishes the axon and its supporting (insulating) structure called the myelin, but it is the interruption of the proteins within this structure that causes the symptoms of end organ damage and eventual death of the neuron itself. This concept is in contradistinction of neuron death by all other direct insults to the nerve cell itself, for example, in trauma or when poliomyelitis destroys neurons through viral disease.

My concern here is to explore how inflammation and your body’s natural defenses lead to compression of the nerves themselves. A good example is the wrist, where the neurovascular bundle (artery, vein, and nerve) passes through a narrow, bony tunnel. Compression in this tight area leads to the hand pain, tingling, and loss of sensation seen in carpal tunnel syndrome. Any compression around a neurovascular bundle in a fibro-osseous tunnel^* ends up restricting healthy blood flow to the nerves. This leads to malfunction of whatever the neurovascular bundle connects to—the end organ. If your nerves don’t get a fresh blood flow, they’re starved for oxygen and other nutrients and their waste products don’t get efficiently carried away.

Think of it this way. Your nerves conduct electrical messages just as an electrical cord conducts electricity. Turn off the power or dial back the dimmer switch and the lights go out or begin to fade. That’s what’s happening with your nerves. As your body struggles to deal with the inflammatory impact of sugar, your nerves become damaged, swollen, and compressed as they pass through fibro-osseous tunnels in your body. As they are compressed, they essentially begin to flicker—like when insulation around an electrical wire gets wet. The current no longer flows steadily and nerves become less and less effective in carrying out their essential function of relaying important messages from your brain to muscles and organs throughout your body. Again, the ultimate result is damage to the end organs: the gangrenous toe, the blind eye, the damaged heart.

How Your Nerves Work

Imagine arriving at an ocean beach on a hot day. You cross blistering pavement in the parking lot and step onto the sand to remove your shoes and socks. Immediately you feel the raspy texture and unstable footing below as you walk across the hot, rough surface to find a nice, smooth spot to spread your beach blanket. Then down to the water, and as you go, your feet begin to cool even as you may also feel the occasional sharp or blunt edge of a seashell. You feel the changing texture of the sand, along with the cold water as it washes over your feet. All this time, you’ve been unconsciously balancing yourself to compensate for the changing surfaces—while sensing temperature, pressure, vibration, touch, and pain.

These sensations and that proprioception (knowing where you are in relationship to your environment) start with tiny cells in the skin on the soles of your feet. I’m going to focus here on the way you perceive sensations, not your whole nervous system (that would be another book). So, here we’re talking about the nerves of your afferent nervous system—the ones that perceive sensations and send messages about them to your spinal cord and brain. I’m also going to focus just on the nerves that affect your feet, although pretty much everything I’ll discuss also applies to the rest of your body.

Sending messages about touch, temperature, pressure, and pain starts just under the surface of your skin with several different types of receptors:

•  Mechanical receptors sense stimulation by pressure, such as stepping on the sharp edge of a seashell.

•  Thermal receptors sense temperature changes.

•  Polymodal receptors sense unpleasant stimuli, such as pain.

•  In skin that doesn’t have hair, like the soles of your feet, you have two main kinds of mechanical receptors: Merkel cells, which sense changes in pressure, texture, and location, and Meissner’s corpuscles, which sense light touch and vibration. You have two types of thermal receptors: one to detect cold and one to detect heat. Messages about pain also start just under the skin surface through tiny nerve endings called nociceptors.

All of this simply means that when a receptor senses something—when you step on a pebble, for instance—that mechanical message gets converted to an electrical impulse that’s relayed up the line to your spinal cord and brain through nerve fibers. You feel the shape, size, and sharpness of the pebble underfoot because your nerves are relaying those important messages.

We’re talking about feet here, but the part of your body with the most Merkel cells is your hand. In fact, that’s what your fingerprints were designed for: Merkel cells cluster under the raised ridges. When you pick up a hot cup of coffee, Merkel cells are what make your fingers so exquisitely sensitive to touch and pressure. These important nerves are how you feel the shape and texture of the cup, which enables you to grasp it effectively. The Meissner corpuscles do the same for the perception of movement and vibration as the Merkel cells do for touch and pressure. Stop for a minute and pick up an object—a cup, a rock, a book, anything will do. Close your eyes and think of all of the ways that you know what you are holding: the shape, the temperature, the texture, whether it’s wet or dry, etc.

You have similar raised ridges on the soles of your feet.

In another analogy, Merkel receptors are like pixels. The more pixels your screen has, the clearer the picture. The more functioning Merkel receptors you have, the clearer your sensations of shape, texture, or pain. Long-term nerve damage from sugar destroys these receptors and as they die, the picture gets increasingly fuzzy. When your nerves can’t adequately read the surface beneath your feet, all kinds of problems begin to arise. You lose your balance and you can’t feel pain, so you don’t necessarily know when you’ve hurt yourself.

Nerve Fibers

When axons bind together, they form nerve fibers. These structures come in several types as well, but we’ll focus here on the two most important kinds: type A delta fibers and type C fibers.

Type A Delta Fibers

Type A delta fibers are sensory nerve fibers. They’re myelinated, meaning they’re wrapped in a thin layer of a fatty substance called myelin. For the A delta fiber, myelin acts much as insulation does on a wire carrying electricity. Myelinated nerves conduct sensory information quickly. When you step on something sharp and cut your foot, the A delta fibers send the message to your brain and you feel a sharp pain almost instantly. Likewise, if you dip your foot into the cold ocean, you feel the sensation of cold very quickly.

Type C Fibers

Type C fibers are also sensory nerve fibers, but they’re unmyelinated and are much thinner than A fibers, and so they transmit sensory information more slowly. They also need a stronger stimulus to go into action. In general, C fibers are responsible for telling your brain about sensations such as burning pain, temperature, and itchiness. When you have a dull ache or chronic pain, your C fibers are relaying the message.

When you look at how tiny all these receptors and nerve fibers are, it’s easy to see how too much sugar in your bloodstream can damage them. A Merkel cell is cup-shaped and only about 10 micrometers in diameter.^* C fibers are only 0.2 to 1.5 micrometers in diameter. When very thin, unmyelinated nerve fibers are constantly bombarded with excess glucose, they easily get glycated, or clogged up with oxidized glucose that sticks to them, just as caramel candy sticks to your teeth. The A delta nerve fibers are myelinated, so they get damaged when too much glucose makes them swell up and compresses them within the myelin sheath. Too much sugar can even make A delta fibers demyelinate and lose some of their fatty sheath.

And with every type of receptor and nerve fiber, excess sugar keeps the blood vessels that nourish them from expanding and contracting normally—the blood flow is uneven or even blocked, causing further damage. Eventually, when the nerves are damaged enough, they stop conducting, leaving you with permanent numbness.

When your sensory receptors aren’t working well, you don’t feel things properly. You might not notice that a fold in your sock is giving you a blister, for instance. Alternatively, the sensory receptors can become supersensitive and start overreacting to or even imagining sensations. That’s when your feet might become very sensitive to heat or cold or you might feel as if you have a pebble in your shoe even though you don’t.

And when your nerve fibers aren’t transmitting messages up the line from the receptors very well, it’s like a blurry picture, or static on the line. Some messages don’t get through at all, causing areas of numbness. Other messages get distorted or amplified, causing pain, itching, and burning. If the larger A fibers have started to demyelinate, it’s like having cracks in the insulation of an electrical wire—you get a short circuit that might even cause a fire. That’s pretty much what happens to your nerves when they demyelinate.

More interesting, perhaps, is that when any of the afferent nerves are damaged, they don’t need a signal from a sensory receptor to send a message. They can start firing off at random with the sharp, sudden pains that are so characteristic of diabetic peripheral neuropathy. They can also become hyperactive and extremely sensitive, sending a signal of severe pain from even the lightest touch. Some of my neuropathy patients can’t stand the touch of even a bedsheet on their feet; others are supersensitive to heat or cold. Let’s drill down even deeper into how all this happens.

Three Key Chemical Pathways

Over the years, all of that extra glucose has literally been gumming up your nerves through inflammation and scarring. Such inflammation occurs over three main pathways: the Maillard reaction, the polyol pathway, and the nitric oxide pathway.

The Maillard Reaction

The Maillard reaction is the chemical interaction^* between glucose and amino acids whose result we recognize in flavorful brown food, like corn roasted on a grill or what happens to turkey skin in a hot oven. Named after French chemist Louis-Camille Maillard, who first described it in 1912, the Maillard reaction also takes place in the human body, where it’s called glycation. Glycation occurs when glucose in your system reacts with proteins, fats, or nucleic acids (DNA) to produce advanced glycation end products (aptly abbreviated AGEs). They’re produced when a protein reacts with sugar, resulting in damaged, cross-linked proteins—causing them to become stiff and malformed. On your skin, this results in wrinkles and age spots. Imagine the same internal reaction throughout your body and you have an idea of what AGEs are doing to you.

AGEs are a toxic form of scar tissue—keeping the nerves from functioning properly and causing lesions. As the body tries to protect itself by breaking these AGEs apart, immune cells secrete large amounts of inflammatory chemicals. Many of the diseases we think of as a part of aging are actually caused by this process. Depending upon where the AGEs occur, the result can be arthritis, heart disease, cataracts, memory loss, wrinkled skin, or complications of diabetes—such as peripheral neuropathy. One way to look at it is that you’re slowly cooking your nerves to death, just like that turkey in the oven.

The Polyol Pathway

When you have more glucose in your system than your body can use or store, your body has to get rid of it some other way. So it reverts to the fallback method: glucose is metabolized through a complex process called the polyol pathway. We don’t need to go into all the details of the pathway, because the damage to your nerves happens right at the start, when the glucose gets broken down via an enzyme (or biological catalyst) called aldose reductase into a substance called sorbitol. Sound familiar? It should. Commercially derived from stone fruits, seaweed, and—you guessed it—corn, sorbitol is often labeled as an “organic sweetener” in low-cal processed foods, dietetic candy, and imitation crab, to name but a few.

Sorbitol cannot pass through cell membranes, which means that it gets stuck wherever it’s made. And because sorbitol is chemically related to sugar, it attracts water. (Think of your sugar bowl on a humid day.) When sorbitol starts to build up inside a cell, it also draws in water, which makes that cell swell up. The swelling itself is bad, because it reduces blood flow to the nerve, starving it of nutrients and oxygen. But when the swelling occurs in places where the nerves pass through a tight tunnel, such as your wrist or ankle, there’s not enough room. The nerve gets compressed within the tunnel, causing pain, numbness, and all the other symptoms of neuropathy.

The Maillard reaction and the polyol pathway are two processes that are well understood and well documented in the medical literature. There is nothing new or surprising about them. The next part, however, about the nitric oxide pathway, is new.

The Nitric Oxide Pathway

Your blood vessels have an inner lining called the endothelium. An essential amino acid in your blood, L-arginine, goes through a complex process involving the enzyme nitric oxide synthase (NOS) and converts into the gas nitric oxide. When the endothelium releases this gas, it causes your blood vessels to relax and your blood flows freely through the vessel.^*

When the endothelium is damaged, it can’t create nitric oxide as well, which means your blood vessels don’t relax as they should. How does the endothelium get damaged? As with every other chemical reaction in your body, the answer is complex—but in this case, the molecule asymmetric dimethylarginine (ADMA) is an important factor.

Hang on, we’re almost there.

An amino acid found naturally in your body, ADMA is structurally very similar to L-arginine. We could call them cousins. And so both ADMA and L-arginine can attach to the enzyme nitric oxide synthase (NOS).

When L-arginine attaches, it converts to nitric oxide and your vessels function the way they should. When ADMA attaches, however, it converts to peroxynitrite,^* which clogs the conversion and blocks the production of nitric oxide. (Not good.) Technically speaking, ADMA inhibits nitric oxide synthesis. Too much ADMA in your blood (also linked to insulin resistance) causes your blood vessels to constrict rather than dilate.

You Can See Where I’m Going

Here’s how I believe inflammation and scarring from sugar causes nerve damage:

1.  Too much sugar triggers inflammation in your blood vessels and causes the Maillard reaction, or glycation: the slow-sugar-cooking of proteins in your body. Among other things, this makes the endothelium rough and sticky, rather than smooth. As Cooke noted, it becomes more like Velcro than Teflon.

2.  When sugar is processed into sorbitol, it enters your nerves through the polyol pathway and gets stuck there. The sorbitol causes your nerves to absorb water and swell. When there’s no room for them to expand further, the nerve gets compressed against the surrounding bone and tissue. The pressure causes pain and numbness. In addition, the swollen nerve gets less oxygen and nutrients as it gradually stops conducting effectively.

3.  The nitric oxide pathway is blocked by high levels of asymmetric dimethylarginine (ADMA). This causes the blood vessels to constrict, which reduces blood flow to the nerve—and reduced blood flow means that the tiny blood vessels bringing nutrients and oxygen to your nerves constrict and then clog up.

A relatively minor amount of constriction can lead to a disproportionately large impact on flow. According to Poiseuille’s law,^* a 19 percent reduction in the radius of the vessel will reduce blood flow by 50 percent.

Think of the implications. Less than 20 percent constriction results in blood flow being cut in half. And when nutrient- and oxygen-rich blood can’t get to your nerves, they suffocate and black out, slowly and painfully.

Back to Global Compression

The takeaway is that such mechanisms are at work everywhere in your body and account for such diverse problems as irritable bowel syndrome, migraines, and macular degeneration. To see the complete picture of what happens when you eat sugar, it’s important to remember that your nerves are essential messengers throughout your body. They fulfill roles that extend well beyond the sense of touch, carrying critical messages to and from every muscle and organ in the body. When those messages are impaired, muscles don’t work properly and organs fail. Even if you never experience an appendectomy, a similar story applies to the bodily mechanisms behind other end organ ailments. The nerves that control the large intestine, for example, can become damaged, and lead to the alternating diarrhea and constipation that are the most common symptoms of irritable bowel syndrome. Headaches are similar in that the occipital nerves controlling muscles in the head can become irritated and entrapped, just as the nerves controlling the gallbladder or the big toe in diabetic peripheral neuropathy.

All nerves are irritated by the effects of sugar and ultimately damage important muscles that control the functioning of your organs.